GPS2

G protein pathway suppressor 2, the group of NCoR/SMRT transcriptional repression complex subunits

Basic information

Region (hg38): 17:7311324-7315564

Links

ENSG00000132522 ∙ NCBI:2874 ∙ OMIM:601935 ∙ HGNC:4550 ∙ Uniprot:Q13227 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPS2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	9	0	0

Variants in GPS2

This is a list of pathogenic ClinVar variants found in the GPS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-7311367-T-TG		EIF5A-related disorder	Uncertain significance (Jun 22, 2023)
17-7311395-G-A			Pathogenic (Apr 24, 2024)
17-7311402-T-TA		Faundes-Banka syndrome	Pathogenic (Jan 18, 2024)
17-7311404-C-G		Faundes-Banka syndrome	Pathogenic (Jun 09, 2021)
17-7311404-C-T		Faundes-Banka syndrome	Pathogenic (Dec 28, 2023)
17-7311416-C-T			Uncertain significance (Oct 24, 2023)
17-7311422-C-T			Likely pathogenic (Apr 03, 2023)
17-7311422-CCT-C			Likely pathogenic (Apr 01, 2024)
17-7311574-C-T		not specified	Likely benign (Nov 01, 2017)
17-7311583-G-A			Likely benign (Oct 01, 2023)
17-7311587-C-A		not specified	Uncertain significance (Jun 16, 2024)
17-7311590-TC-AT		Faundes-Banka syndrome	Likely pathogenic (Apr 17, 2023)
17-7313037-C-G		not specified	Uncertain significance (Aug 31, 2022)
17-7313044-C-T		not specified	Uncertain significance (Mar 21, 2023)
17-7313063-G-T		not specified	Uncertain significance (Mar 21, 2023)
17-7313416-A-G		not specified	Uncertain significance (Apr 25, 2022)
17-7313598-G-C		not specified	Uncertain significance (Dec 15, 2023)
17-7313929-T-C		not specified	Uncertain significance (Aug 02, 2021)
17-7314095-G-A		not specified	Uncertain significance (Dec 19, 2022)
17-7314100-G-T		not specified	Uncertain significance (Nov 22, 2022)
17-7314165-G-A			Benign (Dec 31, 2019)
17-7314601-G-A			Benign (Jun 12, 2018)
17-7315025-G-T		not specified	Uncertain significance (Jan 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPS2	protein_coding	protein_coding	ENST00000380728	10	4241

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0532	0.946	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.16	136	180	0.757	0.00000915	2122
Missense in Polyphen		19	17.715	1.0725		206
Synonymous	-4.48	111	65.1	1.71	0.00000321	623
Loss of Function	2.94	6	20.3	0.295	9.60e-7	228

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'-linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:24943844). Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone H3 'Lys-9' (H3K9) demethylation (By similarity). Promotes cholesterol efflux by acting as a transcription coactivator (PubMed:19481530). Acts as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B- cell antigen receptors (BCRs) signaling pathways (By similarity). Acts as a key mediator of mitochondrial stress response: in response to mitochondrial depolarization, relocates from the mitochondria to the nucleus following desumoylation and specifically promotes expression of nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG (PubMed:19858209, PubMed:24943844). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins, thereby preventing N-Cor corepressor complex dissociation (PubMed:20159957). In the cytosol, also plays a non- transcriptional role by regulating insulin signaling and pro- inflammatory pathways (By similarity). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the proinflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (By similarity). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (By similarity). Able to suppress G-protein- and mitogen-activated protein kinase- mediated signal transduction (PubMed:8943324). Acts as a tumor- suppressor in liposarcoma (PubMed:27460081). {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:19858209, ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:27460081, ECO:0000269|PubMed:29499132, ECO:0000269|PubMed:8943324}.
• Pathway: HTLV-I infection - Homo sapiens (human);HDACs deacetylate histones;Chromatin modifying enzymes;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.0705

Intolerance Scores

• loftool: 0.499
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.0968
• hipred: Y
• hipred_score: 0.580
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gps2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;inactivation of MAPK activity;JNK cascade;negative regulation of tumor necrosis factor-mediated signaling pathway;positive regulation of cholesterol efflux;viral process;regulation of lipid metabolic process;B cell differentiation;negative regulation of toll-like receptor signaling pathway;negative regulation of GTPase activity;positive regulation of peroxisome proliferator activated receptor signaling pathway;regulation of fat cell differentiation;negative regulation of fat cell differentiation;positive regulation of transcription by RNA polymerase II;negative regulation of JNK cascade;negative regulation of inflammatory response;negative regulation of B cell receptor signaling pathway;response to mitochondrial depolarisation;negative regulation of protein K63-linked ubiquitination
• Cellular component: nucleus;nucleoplasm;mitochondrion;cytosol;transcriptional repressor complex
• Molecular function: transcription coactivator activity;transcription corepressor activity;GTPase inhibitor activity;protein binding;cyclin binding