RGS5

protein-coding

regulator of G protein signaling 5, the group of Regulators of G-protein signaling

Gene summary

This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

MANE transcript

NM_003617.4

Inheritance

—

ClinVar variants

U:24B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr1:163,111,121-163,321,791

External References & Databases

Ensembl (ENSG00000143248)

Transcript & Mutation Effects

hg38 • Region Span ~210.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

essential hypertension, geneticNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007781

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RGS5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 22

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003617.4. 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					1 clinvar	1
missense			22 clinvar			22
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	24	0	1	25

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003617.4	RefSeq	NP_003608.1	5	MANE Select
ENST00000313961.10	Ensembl	ENSP00000319308.5	5	MANE Select
NM_001195303.3	RefSeq	NP_001182232.1	2	Standard
NM_001254748.2	RefSeq	NP_001241677.1	2	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

Cellular Component

cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000530507
Coding exons: 5
Length: 210667
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125743
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.149	91	95.1	0.957	0.00000478	1228
Missense (PolyPhen)		25	28.534	0.87615		391
Synonymous	1.46	25	36.2	0.691	0.00000190	330
Loss of Function	0.866	6	8.77	0.684	3.68e-7	118

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.00033	0.00033	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 to G(i)-alpha and G(o)-alpha, but not to G(s)-alpha (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.223

Intolerance Scores

LoFtool: 0.749
RVIS EVS: 0.04
RVIS percentile EVS: 56.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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