RGS21

protein-coding

regulator of G protein signaling 21, the group of Regulators of G-protein signaling

Gene summary

Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins are GTPase-activating proteins for Gi (see GNAI1; MIM 139310) and Gq (see GNAQ; MIM 600998) class G-alpha proteins. They accelerate transit through the cycle of GTP binding and hydrolysis and thereby accelerate signaling kinetics and termination.[supplied by OMIM, Nov 2008]

MANE transcript

NM_001039152.3

Inheritance

—

ClinVar variants

U:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr1:192,316,992-192,367,285

External References & Databases

Ensembl (ENSG00000253148)

Transcript & Mutation Effects

hg38 • Region Span ~50.3 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 RGS21 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039152.3. 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						0
missense			20 clinvar			20
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	20	0	0	20

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039152.3	RefSeq	NP_001034241.1	4	MANE Select
ENST00000417209.2	Ensembl	ENSP00000428343.1	4	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
G alpha (i) signalling events
G alpha (q) signalling events
GPCR downstream signalling

Biological Process

negative regulation of signal transduction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417209
Coding exons: 4
Length: 50294
Individuals with no LoFs: 124664
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 124711
p: 0.000188

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.359	86	77.1	1.12	0.00000374	1013
Missense (PolyPhen)		39	32.444	1.2021		417
Synonymous	0.141	26	26.9	0.965	0.00000146	259
Loss of Function	0.233	7	7.70	0.909	4.46e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00025	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0011	0.0011	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000033	0.000033	rare
Other	0.00018	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.730
RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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