RGS1
protein-codingregulator of G protein signaling 1, the group of Regulators of G-protein signaling
Gene summary
This gene encodes a member of the regulator of G-protein signalling family. This protein is located on the cytosolic side of the plasma membrane and contains a conserved, 120 amino acid motif called the RGS domain. The protein attenuates the signalling 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]
- IER1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.3 kbGenCC 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 RGS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002922.4. 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 | 0 | |||||
| missense | 32 | 32 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 33 | 0 | 0 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002913.3 | 5 | MANE Select | |
| Ensembl | ENSP00000356429.3 | 5 | MANE Select | |
| Ensembl | ENSP00000464323.1 | 4 | Standard | |
| Ensembl | ENSP00000569937.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
- Myometrial Relaxation and Contraction Pathways
- TYROBP Causal Network
- Calcium Regulation in the Cardiac Cell
- Signaling by GPCR
Biological Process
- immune response
- signal transduction
- G protein-coupled receptor signaling pathway
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- regulation of G protein-coupled receptor signaling pathway
Molecular Function
- G-protein alpha-subunit binding
- GTPase activator activity
- calmodulin binding
Cellular Component
- cytosol
- plasma membrane
- extrinsic component of cytoplasmic side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367459
- Coding exons
- 5
- Length
- 4305
- Individuals with no LoFs
- 125596
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125603
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.128 | 106 | 110 | 0.966 | 0.00000528 | 1385 |
| Missense (PolyPhen) | 36 | 36.004 | 0.99988 | 471 | ||
| Synonymous | 0.635 | 32 | 36.9 | 0.867 | 0.00000184 | 377 |
| Loss of Function | 2.54 | 1 | 9.39 | 0.107 | 4.58e-7 | 125 |
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 | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the N-formylpeptide chemoattractant receptors and leukotriene receptors (PubMed:10480894). Inhibits B cell chemotaxis toward CXCL12 (By similarity). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form (PubMed:10480894, PubMed:18434541). {ECO:0000250|UniProtKB:Q9JL25, ECO:0000269|PubMed:10480894, ECO:0000269|PubMed:18434541}.;
Recessive Scores
- pRec
- 0.215
Intolerance Scores
- LoFtool
- 0.490
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.763
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |