RGS10

protein-coding

regulator of G protein signaling 10, the group of Regulators of G-protein signaling

Gene summary

Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 10 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. This protein associates specifically with the activated forms of the two related G-protein subunits, G-alphai3 and G-alphaz but fails to interact with the structurally and functionally distinct G-alpha subunits. Regulator of G protein signaling 10 protein is localized in the nucleus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001005339.2

Inheritance

ClinVar variants

U:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr10:119,499,817-119,542,719

External References & Databases

Ensembl (ENSG00000148908)

Transcript & Mutation Effects

hg38 • Region Span ~42.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0021094

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RGS10 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001005339.2. 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)						0
Total	0	0	18	0	0	18

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001005339.2	RefSeq	NP_001005339.1	5	MANE Select
ENST00000369103.3	Ensembl	ENSP00000358099.2	5	MANE Select
NM_002925.4	RefSeq	NP_002916.1	5	Standard
ENST00000369101.7	Ensembl	ENSP00000358097.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
Myometrial Relaxation and Contraction Pathways
Calcium Regulation in the Cardiac Cell
Signaling by GPCR
Signal Transduction

Biological Process

response to amphetamine
G protein-coupled acetylcholine receptor signaling pathway
regulation of G protein-coupled receptor signaling pathway
negative regulation of signal transduction
positive regulation of GTPase activity

Molecular Function

G-protein alpha-subunit binding
GTPase activator activity

Cellular Component

nucleus
cytosol
neuronal cell body
dendritic spine
axon terminus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369103
Coding exons: 5
Length: 42881
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125745
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.33	59	95.7	0.616	0.00000515	1217
Missense (PolyPhen)		13	36.518	0.35599		435
Synonymous	0.974	30	37.6	0.798	0.00000231	301
Loss of Function	2.48	1	9.05	0.110	4.66e-7	111

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the muscarinic acetylcholine receptor CHRM2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:8774883, PubMed:10608901, PubMed:9353196, PubMed:11443111, PubMed:18434541). Modulates the activity of potassium channels that are activated in response to CHRM2 signaling (PubMed:11443111). Activity on GNAZ is inhibited by palmitoylation of the G-protein (PubMed:9353196). {ECO:0000269|PubMed:10608901, ECO:0000269|PubMed:11443111, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:8774883, ECO:0000269|PubMed:9353196}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.435
RVIS EVS: -0.08
RVIS percentile EVS: 47.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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