RGS3

protein-coding

regulator of G protein signaling 3, the group of PDZ domain containing|Regulators of G-protein signaling|C2 domain containing

Gene summary

This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. Long isoforms are largely cytosolic and plasma membrane-associated with a function in Wnt signaling and in the epithelial mesenchymal transition, while shorter N-terminally-truncated isoforms can be nuclear. [provided by RefSeq, Jan 2013]

MANE transcript

NM_001394167.1

Inheritance

—

ClinVar variants

U:182B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr9:113,444,731-113,597,743

External References & Databases

Ensembl (ENSG00000138835)

Transcript & Mutation Effects

hg38 • Region Span ~153.0 kb

Loading mutation effect viewer...

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 RGS3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 176

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394167.1. 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	3 clinvar	1 clinvar	5
missense			169 clinvar	9 clinvar	1 clinvar	179
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	182	12	2	196

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394167.1	RefSeq	NP_001381096.1	23	MANE Select
ENST00000695401.1	Ensembl	ENSP00000511882.1	23	MANE Select
NM_001276260.2	RefSeq	NP_001263189.1	6	Standard
NM_001276261.2	RefSeq	NP_001263190.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rgs3a	Danio rerio	Structure: whole organism Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

rgs3a

Danio rerio

Structure: whole organism

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Myometrial Relaxation and Contraction Pathways
Calcium Regulation in the Cardiac Cell
Signaling by GPCR
Signal Transduction

Biological Process

inactivation of MAPK activity
regulation of G protein-coupled receptor signaling pathway
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding

Cellular Component

nucleoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374140
Coding exons: 25
Length: 153008
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 125748
p: 0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.03	635	712	0.891	0.0000438	7750
Missense (PolyPhen)		197	257.25	0.7658		2709
Synonymous	-0.194	302	298	1.01	0.0000189	2418
Loss of Function	3.78	28	59.5	0.471	0.00000286	702

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00027	0.00026	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0010	0.00098	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00049	0.00048	rare
South Asian	0.00060	0.00059	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form. Down-regulates G- protein-mediated release of inositol phosphates and activation of MAP kinases. {ECO:0000269|PubMed:10749886, ECO:0000269|PubMed:11294858, ECO:0000269|PubMed:8602223, ECO:0000269|PubMed:9858594}.;

Intolerance Scores

LoFtool: 0.909
RVIS EVS: -0.36
RVIS percentile EVS: 29.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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