RGS12

protein-coding

regulator of G protein signaling 12, the group of PDZ domain containing|Regulators of G-protein signaling

Gene summary

This gene encodes a member of the 'regulator of G protein signaling' (RGS) gene family. The encoded protein may function as a guanosine triphosphatase (GTPase)-activating protein as well as a transcriptional repressor. This protein may play a role in tumorigenesis. Multiple transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001394154.1

Inheritance

—

ClinVar variants

U:251B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr4:3,293,021-3,439,913

External References & Databases

Ensembl (ENSG00000159788)

Transcript & Mutation Effects

hg38 • Region Span ~146.9 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 RGS12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 255

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394154.1. 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			3 clinvar	4 clinvar	1 clinvar	8
missense			243 clinvar	16 clinvar		259
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	251	20	1	272

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394154.1	RefSeq	NP_001381083.1	17	MANE Select
ENST00000336727.8	Ensembl	ENSP00000338509.4	17	MANE Select
NM_001394155.1	RefSeq	NP_001381084.1	17	Standard
NM_001394156.1	RefSeq	NP_001381085.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
GPCR signaling-G alpha q
GPCR signaling-cholera toxin
GPCR signaling-pertussis toxin

Biological Process

signal transduction
regulation of G protein-coupled receptor signaling pathway
negative regulation of signal transduction
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
GTPase regulator activity

Cellular Component

condensed nuclear chromosome
nucleus
nucleolus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344733
Coding exons: 17
Length: 146886
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125748
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.614	873	926	0.943	0.0000609	9426
Missense (PolyPhen)		264	325.53	0.81098		3173
Synonymous	-1.39	439	403	1.09	0.0000299	2974
Loss of Function	3.94	24	55.7	0.431	0.00000309	608

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00044	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00025	0.00023	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. {ECO:0000250|UniProtKB:O08774}.;

Intolerance Scores

LoFtool: 0.604
RVIS EVS: -0.46
RVIS percentile EVS: 23.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.652

Gene Damage Prediction

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