GPSM1

protein-coding

G protein signaling modulator 1, the group of Tetratricopeptide repeat domain containing

Gene summary

G-protein signaling modulators (GPSMs) play diverse functional roles through their interaction with G-protein subunits. This gene encodes a receptor-independent activator of G protein signaling, which is one of several factors that influence the basal activity of G-protein signaling systems. The protein contains seven tetratricopeptide repeats in its N-terminal half and four G-protein regulatory (GPR) motifs in its C-terminal half. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_001145638.3

Inheritance

—

ClinVar variants

U:149B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr9:136,327,476-136,359,605

External References & Databases

Ensembl (ENSG00000160360)

Transcript & Mutation Effects

hg38 • Region Span ~32.1 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 GPSM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 148

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001145638.3. 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			146 clinvar	2 clinvar		148
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	149	3	0	152

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001145638.3	RefSeq	NP_001139110.2	14	MANE Select
ENST00000440944.6	Ensembl	ENSP00000392828.1	14	MANE Select
NM_001145639.2	RefSeq	NP_001139111.1	3	Standard
NM_001200003.2	RefSeq	NP_001186932.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cocaine addiction - Homo sapiens (human)
Signaling by GPCR
Signal Transduction
G alpha (i) signalling events
GPCR downstream signalling

Biological Process

nervous system development
positive regulation of macroautophagy
cell differentiation
negative regulation of GTPase activity
negative regulation of guanyl-nucleotide exchange factor activity

Molecular Function

GDP-dissociation inhibitor activity
protein binding

Cellular Component

Golgi membrane
endoplasmic reticulum membrane
cytosol
plasma membrane
cell cortex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000440944
Coding exons: 14
Length: 32126
Individuals with no LoFs: 125426
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125439
p: 0.0000518

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.395	420	443	0.947	0.0000316	4292
Missense (PolyPhen)		178	182.55	0.97506		1784
Synonymous	0.149	211	214	0.987	0.0000175	1354
Loss of Function	2.90	13	30.2	0.430	0.00000154	338

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G- protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction. {ECO:0000269|PubMed:11024022, ECO:0000269|PubMed:12642577}.;

Recessive Scores

pRec: 0.129

Intolerance Scores

LoFtool: 0.0682
RVIS EVS: -1.32
RVIS percentile EVS: 4.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.807

Gene Damage Prediction

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