GPS1

G protein pathway suppressor 1, the group of COP9 signalosome

Basic information

Region (hg38): 17:82050690-82057470

Links

ENSG00000169727 ∙ NCBI:2873 ∙ OMIM:601934 ∙ HGNC:4549 ∙ Uniprot:Q13098 ∙ 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 GPS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPS1 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				1	2	3
missense			17	1		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	17	2	2

Variants in GPS1

This is a list of pathogenic ClinVar variants found in the GPS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-82050705-T-C		not specified	Uncertain significance (Dec 03, 2021)
17-82050728-C-T		not specified	Likely benign (Jan 03, 2024)
17-82051552-C-G		not specified	Uncertain significance (Aug 16, 2022)
17-82051565-G-A		not specified	Uncertain significance (Apr 12, 2022)
17-82051566-G-A			Benign (Dec 31, 2019)
17-82051589-C-T		not specified	Uncertain significance (Jun 17, 2024)
17-82051600-C-T		not specified	Uncertain significance (Mar 24, 2023)
17-82051601-G-A		not specified	Uncertain significance (Mar 30, 2024)
17-82051612-G-A		not specified	Uncertain significance (May 20, 2024)
17-82051761-G-A			Likely benign (Oct 01, 2022)
17-82052335-C-T		not specified	Uncertain significance (Mar 28, 2024)
17-82052344-C-T		not specified	Uncertain significance (Aug 21, 2023)
17-82052367-C-T		not specified	Uncertain significance (May 06, 2024)
17-82052433-C-G		not specified	Uncertain significance (Apr 18, 2023)
17-82053890-G-A		not specified	Uncertain significance (Jul 31, 2023)
17-82053898-G-A		not specified	Uncertain significance (Mar 01, 2024)
17-82053918-G-A			Likely benign (Jul 01, 2022)
17-82053947-C-T		not specified	Uncertain significance (Dec 08, 2023)
17-82053994-A-G		not specified	Uncertain significance (Dec 09, 2023)
17-82054010-T-C		not specified	Uncertain significance (Jun 17, 2024)
17-82054033-C-G		not specified	Uncertain significance (Aug 28, 2023)
17-82054042-G-A		not specified	Uncertain significance (Jul 12, 2023)
17-82054546-C-A		not specified	Uncertain significance (Apr 04, 2023)
17-82054573-G-A			Benign (Sep 10, 2018)
17-82054634-C-T			Benign (Apr 03, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPS1	protein_coding	protein_coding	ENST00000392358	13	6780

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00181	125374	0	9	125383	0.0000359

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.86	235	330	0.712	0.0000211	3430
Missense in Polyphen		40	96.996	0.41239		954
Synonymous	-3.30	195	145	1.35	0.0000101	1023
Loss of Function	4.48	2	27.3	0.0734	0.00000133	311

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000105	0.0000995
East Asian	0.00	0.00
Finnish	0.0000481	0.0000462
European (Non-Finnish)	0.0000460	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN- dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Suppresses G- protein- and mitogen-activated protein kinase-mediated signal transduction. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:9535219}.
• Pathway: DNA Repair;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Clathrin-mediated endocytosis;Neddylation;Cargo recognition for clathrin-mediated endocytosis;DNA Damage Recognition in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Formation of TC-NER Pre-Incision Complex;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.0897

Intolerance Scores

• loftool: 0.0511
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.43

Haploinsufficiency Scores

• pHI: 0.245
• hipred: Y
• hipred_score: 0.728
• ghis: 0.579

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.770

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gps1
• Phenotype: embryo phenotype; liver/biliary system 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: inactivation of MAPK activity;protein deneddylation;nucleotide-excision repair, DNA damage recognition;transcription-coupled nucleotide-excision repair;JNK cascade;negative regulation of GTPase activity;post-translational protein modification
• Cellular component: nucleoplasm;cytosol;COP9 signalosome
• Molecular function: GTPase inhibitor activity;protein binding