GPS1

protein-coding

G protein pathway suppressor 1, the group of COP9 signalosome

Gene summary

This gene is known to suppress G-protein and mitogen-activated signal transduction in mammalian cells. The encoded protein shares significant similarity with Arabidopsis FUS6, which is a regulator of light-mediated signal transduction in plant cells. [provided by RefSeq, Mar 2016]

MANE transcript

NM_001321092.3

Inheritance

—

ClinVar variants

U:49B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr17:82,050,691-82,057,470

External References & Databases

Ensembl (ENSG00000169727)

Transcript & Mutation Effects

hg38 • Region Span ~6.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321092.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			45 clinvar	1 clinvar		46
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	2	1	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 165 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321092.3	RefSeq	NP_001308021.1	13	MANE Select
ENST00000578552.6	Ensembl	ENSP00000462265.1	13	MANE Select
NM_001321089.3	RefSeq	NP_001308018.1	14	Standard
NM_001321090.3	RefSeq	NP_001308019.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

DNA Repair
Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification
Metabolism of proteins

Biological Process

inactivation of MAPK activity
protein deneddylation
nucleotide-excision repair, DNA damage recognition
transcription-coupled nucleotide-excision repair
JNK cascade

Molecular Function

GTPase inhibitor activity
protein binding

Cellular Component

nucleoplasm
cytosol
COP9 signalosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392358
Coding exons: 13
Length: 6780
Individuals with no LoFs: 125374
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125383
p: 0.0000359

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.86	235	330	0.712	0.0000211	3430
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00011	0.00010	rare
East Asian	0	0.0	absent
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0897

Intolerance Scores

LoFtool: 0.0511
RVIS EVS: -0.89
RVIS percentile EVS: 10.43

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.770

Gene Damage Prediction

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