GenomeRNAi - a database for RNAi phenotypes and reagents

Phenotype information for gene 6392 (SDHD)

Screen TitleGene IDGene SymbolReagent IDScorePhenotypeFollow Up
Proliferation of cells with active beta-catenin (2)
SDHD
TRCN0000039847
 -0,07
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Ciliogenesis and cilium length (1)
6392
SDHD
142567
 np
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Melanogenesis
NM_003002
SDHD
np
 0,92
​		 none no

Reference

Genome-wide siRNA-based functional genomics of pigmentation identifies novel genes and pathways that impact melanogenesis in human cells. Ganesan et al., 2008

Melanin protects the skin and eyes from the harmful effects of UV irradiation, protects neural cells from toxic insults, and is required for sound conduction in the inner ear. Aberrant regulation of melanogenesis underlies skin disorders (melasma and vitiligo), neurologic disorders (Parkinson''s disease), auditory disorders (Waardenburg''s syndrome), and opthalmologic disorders (age related macular degeneration). Much of the core synthetic machinery driving melanin production has been identified; however, the spectrum of gene products participating in melanogenesis in different physiological niches is poorly understood. Functional genomics based on RNA-mediated interference (RNAi) provides the opportunity to derive unbiased comprehensive collections of pharmaceutically tractable single gene targets supporting melanin production. In this study, we have combined a high-throughput, cell-based, one-well/one-gene screening platform with a genome-wide arrayed synthetic library of chemically synthesized, small interfering RNAs to identify novel biological pathways that govern melanin biogenesis in human melanocytes. Ninety-two novel genes that support pigment production were identified with a low false discovery rate. Secondary validation and preliminary mechanistic studies identified a large panel of targets that converge on tyrosinase expression and stability. Small molecule inhibition of a family of gene products in this class was sufficient to impair chronic tyrosinase expression in pigmented melanoma cells and UV-induced tyrosinase expression in primary melanocytes. Isolation of molecular machinery known to support autophagosome biosynthesis from this screen, together with in vitro and in vivo validation, exposed a close functional relationship between melanogenesis and autophagy. In summary, these studies illustrate the power of RNAi-based functional genomics to identify novel genes, pathways, and pharmacologic agents that impact a biological phenotype and operate outside of preconceived mechanistic relationships.

Screen Details

Stable ID: GR00056-A
Screen Title: Melanogenesis
Assay: Melanin protein expression and viability
Method: Absorbance and luminescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MNT-1
Library: Dharmacon, rp
Reagent Type: siRNA
Score Type: Normalized absorbance ratio
Cutoff: > 2 standard deviations below mean
Notes: Additional information about a secondary screen (retest to determine false-positive rate)

Ciliogenesis and cilium length (1)
6392
SDHD
12437
 -31,72
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Ciliogenesis and cilium length (1)
6392
SDHD
142567
 110,08
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (3)
SDHD
 0,69
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Human papillomavirus oncogene expression regulation (1)
6392
SDHD
 -0,12
​		 none no

Reference

Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Smith et al., 2010

An essential step in the pathogenesis of human papillomavirus (HPV)-associated cancers is the dysregulated expression of the viral oncogenes. The papillomavirus E2 protein can silence the long control region (LCR) promoter that controls viral E6 and E7 oncogene expression. The mechanisms by which E2 represses oncogene expression and the cellular factors through which E2 mediates this silencing are largely unknown. We conducted an unbiased, genome-wide siRNA screen and series of secondary screens that identified 96 cellular genes that contribute to the repression of the HPV LCR. In addition to confirming a role for the E2-binding bromodomain protein Brd4 in E2-mediated silencing, we identified a number of genes that have not previously been implicated in E2 repression, including the demethylase JARID1C/SMCX as well as EP400, a component of the NuA4/TIP60 histone acetyltransferase complex. Each of these genes contributes independently and additively to E2-mediated silencing, indicating that E2 functions through several distinct cellular complexes to repress E6 and E7 expression.

Screen Details

Stable ID: GR00197-A-1
Screen Title: Human papillomavirus oncogene expression regulation (1)
Assay: HPV18 LCR reporter activity
Method: Luminescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: C33A/BE2/18LCR c4
Library: Dharmacon, Human siGENOME SMARTpool library
Reagent Type: siRNA
Score Type: Z-score
Cutoff: >= 2
Notes: Author-submitted data; Phenotype strength according to Z-scores: weak: 2 - 3; moderate: 3 - 5; strong: > 5

Proliferation of cells with active beta-catenin (4)
SDHD
TRCN0000039844
 -2,08
​		 Decreased viability no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (1)
SDHD
 -0,6
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
SDHD
TRCN0000039847
 -0,06
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Cell cycle
SDHD
shSDHD-266
 20,1
​		 Increased mitotic index no

Reference

A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Moffat et al., 2006

To enable arrayed or pooled loss-of-function screens in a wide range of mammalian cell types, including primary and nondividing cells, we are developing lentiviral short hairpin RNA (shRNA) libraries targeting the human and murine genomes. The libraries currently contain 104,000 vectors, targeting each of 22,000 human and mouse genes with multiple sequence-verified constructs. To test the utility of the library for arrayed screens, we developed a screen based on high-content imaging to identify genes required for mitotic progression in human cancer cells and applied it to an arrayed set of 5,000 unique shRNA-expressing lentiviruses that target 1,028 human genes. The screen identified several known and approximately 100 candidate regulators of mitotic progression and proliferation; the availability of multiple shRNAs targeting the same gene facilitated functional validation of putative hits. This work provides a widely applicable resource for loss-of-function screens, as well as a roadmap for its application to biological discovery.

Screen Details

Stable ID: GR00110-A-0
Screen Title: Cell cycle
Assay: Mitotic index
Method: High content (microscopy)
Scope:
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HT29 (colon cancer)
Library: , TRC shRNA library
Reagent Type: shRNA
Score Type: Mitotic index
Cutoff: >=14 / <= 0.3
Notes:

Ciliogenesis and cilium length (1)
6392
SDHD
12532
 -43,53
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (4)
SDHD
 -0,71
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Ciliogenesis and cilium length (1)
6392
SDHD
12532
 -41,99
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (1)
SDHD
TRCN0000039847
 0,35
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
SDHD
 -0,24
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (2)
SDHD
 -0,15
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Ciliogenesis and cilium length (1)
6392
SDHD
12622
 14,96
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Ciliogenesis and cilium length (1)
6392
SDHD
12437
 -19,39
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Hepatitis C virus replication (1)
6392
SDHD
PL-50024
 0,9
​		 none no

Reference

A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Tai et al., 2009

Hepatitis C virus (HCV) chronically infects 3% of the world''s population, and complications from HCV are the leading indication for liver transplantation. Given the need for better anti-HCV therapies, one strategy is to identify and target cellular cofactors of the virus lifecycle. Using a genome-wide siRNA library, we identified 96 human genes that support HCV replication, with a significant number of them being involved in vesicle organization and biogenesis. Phosphatidylinositol 4-kinase PI4KA and multiple subunits of the COPI vesicle coat complex were among the genes identified. Consistent with this, pharmacologic inhibitors of COPI and PI4KA blocked HCV replication. Targeting hepcidin, a peptide critical for iron homeostasis, also affected HCV replication, which may explain the known dysregulation of iron homeostasis in HCV infection. The host cofactors for HCV replication identified in this study should serve as a useful resource in delineating new targets for anti-HCV therapies.

Screen Details

Stable ID: GR00180-A-1
Screen Title: Hepatitis C virus replication (1)
Assay: HCV replicon RNA copy number
Method: Luminescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: Huh7/Rep-Feo
Library: Dharmacon, siARRAY Human Genome siRNA Library
Reagent Type: siRNA
Score Type: q-value
Cutoff: Complex criteria
Notes:

Proliferation of cells with active beta-catenin (3)
SDHD
TRCN0000039844
 -0,43
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
SDHD
 0,15
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (2)
SDHD
TRCN0000039844
 -2,32
​		 Decreased viability yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (1)
SDHD
 -0,41
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (2)
SDHD
 0,05
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (1)
SDHD
 0,06
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Combinatorial effect with paclitaxel
NM_003002
SDHD
np
 0,97
​		 none no

Reference

Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Whitehurst et al., 2007

Abundant evidence suggests that a unifying principle governing the molecular pathology of cancer is the co-dependent aberrant regulation of core machinery driving proliferation and suppressing apoptosis. Anomalous proteins engaged in support of this tumorigenic regulatory environment most probably represent optimal intervention targets in a heterogeneous population of cancer cells. The advent of RNA-mediated interference (RNAi)-based functional genomics provides the opportunity to derive unbiased comprehensive collections of validated gene targets supporting critical biological systems outside the framework of preconceived notions of mechanistic relationships. We have combined a high-throughput cell-based one-well/one-gene screening platform with a genome-wide synthetic library of chemically synthesized small interfering RNAs for systematic interrogation of the molecular underpinnings of cancer cell chemoresponsiveness. NCI-H1155, a human non-small-cell lung cancer line, was employed in a paclitaxel-dependent synthetic lethal screen designed to identify gene targets that specifically reduce cell viability in the presence of otherwise sublethal concentrations of paclitaxel. Using a stringent objective statistical algorithm to reduce false discovery rates below 5%, we isolated a panel of 87 genes that represent major focal points of the autonomous response of cancer cells to the abrogation of microtubule dynamics. Here we show that several of these targets sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than otherwise required for a significant response, and we identify mechanistic relationships between cancer-associated aberrant gene expression programmes and the basic cellular machinery required for robust mitotic progression.

Screen Details

Stable ID: GR00054-A
Screen Title: Combinatorial effect with paclitaxel
Assay: Viability (synthetic lethal)
Method: ATP level
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: NCI-H1155
Library: Dharmacon, # G-005000-01
Reagent Type: siRNA
Score Type: Paclitaxel/control ratio
Cutoff: Complex criteria
Notes: Additional information about 87 high-confidence hits

Genome stability
NM_003002
SDHD
np
 sp
​		 none no

Reference

A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Paulsen et al., 2009

Signaling pathways that respond to DNA damage are essential for the maintenance of genome stability and are linked to many diseases, including cancer. Here, a genome-wide siRNA screen was employed to identify additional genes involved in genome stabilization by monitoring phosphorylation of the histone variant H2AX, an early mark of DNA damage. We identified hundreds of genes whose downregulation led to elevated levels of H2AX phosphorylation (gammaH2AX) and revealed links to cellular complexes and to genes with unclassified functions. We demonstrate a widespread role for mRNA-processing factors in preventing DNA damage, which in some cases is caused by aberrant RNA-DNA structures. Furthermore, we connect increased gammaH2AX levels to the neurological disorder Charcot-Marie-Tooth (CMT) syndrome, and we find a role for several CMT proteins in the DNA-damage response. These data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated.

Screen Details

Stable ID: GR00053-A
Screen Title: Genome stability
Assay: gamma-H2AX phosphorylation and DNA content
Method: Fluorescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: ThermoFisher Scientific, siARRAY human genome siRNA library
Reagent Type: siRNA
Score Type: p-value
Cutoff: Complex criteria
Notes: Confidence groupings from 4 to 1 (highest level of confidence in group 4)

Proliferation of cells with active beta-catenin (1)
SDHD
TRCN0000039844
 -2,82
​		 Decreased viability yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (3)
SDHD
 -0,5
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Ciliogenesis and cilium length (1)
6392
SDHD
12622
 11,64
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Self-renewal and pluripotency in human embryonic stem cells (1)
NM_003002
SDHD
 -1,6
​		 none no

Reference

A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Chia et al., 2010

The derivation of human ES cells (hESCs) from human blastocysts represents one of the milestones in stem cell biology. The full potential of hESCs in research and clinical applications requires a detailed understanding of the genetic network that governs the unique properties of hESCs. Here, we report a genome-wide RNA interference screen to identify genes which regulate self-renewal and pluripotency properties in hESCs. Interestingly, functionally distinct complexes involved in transcriptional regulation and chromatin remodelling are among the factors identified in the screen. To understand the roles of these potential regulators of hESCs, we studied transcription factor PRDM14 to gain new insights into its functional roles in the regulation of pluripotency. We showed that PRDM14 regulates directly the expression of key pluripotency gene POU5F1 through its proximal enhancer. Genome-wide location profiling experiments revealed that PRDM14 colocalized extensively with other key transcription factors such as OCT4, NANOG and SOX2, indicating that PRDM14 is integrated into the core transcriptional regulatory network. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Altogether, our study uncovers a wealth of novel hESC regulators wherein PRDM14 exemplifies a key transcription factor required for the maintenance of hESC identity and the reacquisition of pluripotency in human somatic cells.

Screen Details

Stable ID: GR00184-A-1
Screen Title: Self-renewal and pluripotency in human embryonic stem cells (1)
Assay: POU5F1 protein expression
Method: Fluorescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: hESC H1
Library: Dharmacon, SMARTpool siRNA library
Reagent Type: siRNA
Score Type: Z-score
Cutoff: < -2
Notes:

Reagent information for gene 6392 (SDHD)

Reagent IDTypeLibrary
TRCN0000039845 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000036575 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000036578 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000018370 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000039846 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000010501 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000039843 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000036574 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000010500 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000036577 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
D-006305-04 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
D-006305-01 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
D-006305-02 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
D-006305-03 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
SI00713202 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
SI00713195 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
SI00713216 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
SI00713209 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
s12659 siRNA
Ambion Silencer Select|Ambion|1|RefSeq|64781|siRNA|http://www.invitrogen.com/site/us/en/home/brands/ambion.html?CID=fl-ambion
s12660 siRNA
Ambion Silencer Select|Ambion|1|RefSeq|64781|siRNA|http://www.invitrogen.com/site/us/en/home/brands/ambion.html?CID=fl-ambion
s12661 siRNA
Ambion Silencer Select|Ambion|1|RefSeq|64781|siRNA|http://www.invitrogen.com/site/us/en/home/brands/ambion.html?CID=fl-ambion
M-006305-00 siRNA_Pool
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
SP00008069 siRNA_Pool
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/

Gene information for gene 6392 (SDHD)

Gene:
Alternate gene names:PGL1, CBT1, SDH4, PGL
Description:succinate dehydrogenase complex, subunit D, integral membrane protein
Chromosome:11
Start:111957570
Stop:111966517
Strand:positive
Locus:11q23
Biotype:protein-coding
Status:live
Entrez Gene:
GeneCards:
Ensembl:
Hgnc:
Hprd:
Mim:
Uniprot:
Vega:
RefSeq:

Homologs:

GeneChromosomeLocusOrganism
CG102193RDrosophila melanogaster

Genome browser for gene 6392 (SDHD)

Homo sapiens GRCh37
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