RGS17

protein-coding

regulator of G protein signaling 17, the group of Regulators of G-protein signaling

Gene summary

This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012419.5

Inheritance

—

ClinVar variants

U:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr6:153,004,459-153,131,282

External References & Databases

Ensembl (ENSG00000091844)

Transcript & Mutation Effects

hg38 • Region Span ~126.8 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 RGS17 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012419.5. 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						0
missense			18 clinvar			18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	19	0	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012419.5	RefSeq	NP_036551.3	4	MANE Select
ENST00000206262.2	Ensembl	ENSP00000206262.1	4	MANE Select
ENST00000367225.6	Ensembl	ENSP00000356194.1	4	Standard
ENST00000914255.1	Ensembl	ENSP00000584314.1	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

response to amphetamine
negative regulation of signal transduction
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding

Cellular Component

nucleus
cytoplasm
membrane
cell junction
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367225
Coding exons: 4
Length: 126791
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125744
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.937	79	106	0.744	0.00000487	1397
Missense (PolyPhen)		12	29.689	0.40419		401
Synonymous	0.628	30	34.7	0.864	0.00000158	366
Loss of Function	2.42	3	12.1	0.248	7.42e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:15096504). Binds selectively to GNAZ and GNAI2 subunits, accelerates their GTPase activity and regulates their signaling activities. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity). {ECO:0000250|UniProtKB:Q9QZB0, ECO:0000269|PubMed:15096504}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.666
RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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