RGS6

protein-coding

regulator of G protein signaling 6, the group of Regulators of G-protein signaling|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

MANE transcript

NM_001204424.2

Inheritance

ClinVar variants

U:63B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr14:71,932,429-72,566,530

External References & Databases

Ensembl (ENSG00000182732)

Transcript & Mutation Effects

hg38 • Region Span ~634.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RGS6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 59

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001204424.2. 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				13 clinvar		13
missense			63 clinvar	1 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	63	14	0	77

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001204424.2	RefSeq	NP_001191353.1	17	MANE Select
ENST00000553525.6	Ensembl	ENSP00000451030.1	17	MANE Select
NM_001204416.3	RefSeq	NP_001191345.1	17	Standard
NM_001204417.3	RefSeq	NP_001191346.1	17	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
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
Signal Transduction

Biological Process

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

Molecular Function

GTPase activator activity
protein binding

Cellular Component

nucleus
cytosol
plasma membrane
extrinsic component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000553525
Coding exons: 17
Length: 631499
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125747
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.70	198	278	0.713	0.0000153	3259
Missense (PolyPhen)		37	71.228	0.51946		859
Synonymous	0.809	89	99.2	0.897	0.00000586	854
Loss of Function	4.34	8	36.2	0.221	0.00000197	391

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. The RGS6/GNB5 dimer enhances GNAO1 GTPase activity (PubMed:10521509). {ECO:0000269|PubMed:10521509}.;

Recessive Scores

pRec: 0.0980

Intolerance Scores

LoFtool: 0.605
RVIS EVS: -0.67
RVIS percentile EVS: 15.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.555

Gene Damage Prediction

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