RGS2

protein-coding

regulator of G protein signaling 2, the group of Regulators of G-protein signaling|Receptor ligands

Gene summary

Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 2 belongs to this family. The protein acts as a mediator of myeloid differentiation and may play a role in leukemogenesis. [provided by RefSeq, Aug 2009]

Previous symbols:

G0S8

MANE transcript

NM_002923.4

Inheritance

—

ClinVar variants

P:1U:23B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr1:192,809,039-192,812,275

External References & Databases

Ensembl (ENSG00000116741)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 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 RGS2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 18

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002923.4. 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						0
missense			20 clinvar	1 clinvar		21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	0	1	23	1	0	25

Highest pathogenic variant AF is 0.000006816438

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002923.4	RefSeq	NP_002914.1	5	MANE Select
ENST00000235382.7	Ensembl	ENSP00000235382.5	5	MANE Select
ENST00001096534.1	Ensembl	ENSP00000766340.1	3	Standard
ENST00001096535.1	Ensembl	ENSP00000766341.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rgs2	Danio rerio	Structure: migratory neural crest Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

rgs2

Danio rerio

Structure: migratory neural crest

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
cGMP-PKG signaling pathway - Homo sapiens (human)
Olfactory transduction - Homo sapiens (human)
Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway

Biological Process

response to amphetamine
cell cycle
spermatogenesis
brain development
regulation of G protein-coupled receptor signaling pathway

Molecular Function

G-protein alpha-subunit binding
GTPase activator activity
protein binding
calmodulin binding
beta-tubulin binding

Cellular Component

nucleus
nucleolus
cytoplasm
mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000235382
Coding exons: 5
Length: 3235
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0103	105	105	1.00	0.00000513	1409
Missense (PolyPhen)		33	38.93	0.84767		576
Synonymous	-1.02	44	36.2	1.22	0.00000184	357
Loss of Function	0.570	9	11.0	0.815	4.78e-7	146

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:11063746, PubMed:19478087). It is involved in the negative regulation of the angiotensin-activated signaling pathway (PubMed:28784619). Plays a role in the regulation of blood pressure in response to signaling via G protein-coupled receptors and GNAQ. Plays a role in regulating the constriction and relaxation of vascular smooth muscle (By similarity). Binds EIF2B5 and blocks its activity, thereby inhibiting the translation of mRNA into protein (PubMed:19736320). {ECO:0000250|UniProtKB:O08849, ECO:0000269|PubMed:11063746, ECO:0000269|PubMed:11278586, ECO:0000269|PubMed:17901199, ECO:0000269|PubMed:19736320, ECO:0000269|PubMed:28784619, ECO:0000305|PubMed:7643615}.;

Recessive Scores

pRec: 0.268

Intolerance Scores

LoFtool: 0.610
RVIS EVS: -0.16
RVIS percentile EVS: 41.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.838

Gene Damage Prediction

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