RGS20

protein-coding

regulator of G protein signaling 20, the group of Regulators of G-protein signaling

Gene summary

The protein encoded by this gene belongs to the family of regulator of G protein signaling (RGS) proteins, which are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound forms. This protein selectively binds to G(z)-alpha and G(alpha)-i2 subunits, and regulates their signaling activities. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

MANE transcript

NM_003702.5

Inheritance

—

ClinVar variants

U:38B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr8:53,851,795-53,959,303

External References & Databases

Ensembl (ENSG00000147509)

Transcript & Mutation Effects

hg38 • Region Span ~107.5 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 RGS20 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003702.5. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			36 clinvar	1 clinvar		37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	38	2	1	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003702.5	RefSeq	NP_003693.2	5	MANE Select
ENST00000276500.5	Ensembl	ENSP00000276500.4	5	MANE Select
NM_001286673.2	RefSeq	NP_001273602.1	5	Standard
NM_001286674.2	RefSeq	NP_001273603.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Myometrial Relaxation and Contraction Pathways
Calcium Regulation in the Cardiac Cell
Signaling by GPCR
Signal Transduction
GPCR signaling-G alpha q

Biological Process

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

Molecular Function

GTPase activator activity
protein binding

Cellular Component

nucleus
cytoplasm
trans-Golgi network
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297313
Coding exons: 6
Length: 107496
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125736
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.14	167	214	0.781	0.0000110	2508
Missense (PolyPhen)		32	48.666	0.65754		612
Synonymous	0.0535	86	86.6	0.993	0.00000487	774
Loss of Function	1.56	9	15.7	0.574	7.85e-7	172

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000070	0.000062	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

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. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G- protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity). {ECO:0000250, ECO:0000269|PubMed:12379657}.;

Recessive Scores

pRec: 0.0919

Intolerance Scores

LoFtool: 0.775
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.866

Gene Damage Prediction

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