RGS18

protein-coding

regulator of G protein signaling 18, 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 is contains a conserved, 120 amino acid motif called the RGS domain. 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. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_130782.3

Inheritance

ClinVar variants

U:29B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr1:192,158,462-192,185,815

External References & Databases

Ensembl (ENSG00000150681)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited bleeding disorder, platelet-typeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000009

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RGS18 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 30

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_130782.3. 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			29 clinvar	1 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	1	0	30

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_130782.3	RefSeq	NP_570138.1	5	MANE Select
ENST00000367460.4	Ensembl	ENSP00000356430.3	5	MANE Select
ENST00001092794.1	Ensembl	ENSP00000762600.1	5	Standard
ENST00001092795.1	Ensembl	ENSP00000762601.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rgs18	Danio rerio	Structure: thrombocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

rgs18

Danio rerio

Structure: thrombocyte

Quality: decreased amount

abnormal

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

G protein-coupled receptor signaling pathway
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

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367460
Coding exons: 5
Length: 27359
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125740
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0891	119	116	1.02	0.00000556	1555
Missense (PolyPhen)		34	39.424	0.86241		516
Synonymous	0.597	32	36.6	0.874	0.00000157	401
Loss of Function	1.38	6	10.9	0.549	5.57e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	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 to G(i) alpha-1, G(i) alpha- 2, G(i) alpha-3 and G(q) alpha. {ECO:0000269|PubMed:11042171, ECO:0000269|PubMed:11955952}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.596
RVIS EVS: 0.33
RVIS percentile EVS: 73.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.637

Gene Damage Prediction

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