RGS14
protein-codingregulator of G protein signaling 14, 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 one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases 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
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.7 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 RGS14 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006480.5. 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 | 1 | 1 | ||||
| missense | 67 | 5 | 1 | 73 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 71 | 5 | 1 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006471.2 | 15 | MANE Select | |
| Ensembl | ENSP00000386229.3 | 15 | MANE Select | |
| RefSeq | NP_001353546.1 | 15 | Standard | |
| RefSeq | NP_001353547.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rgs14a | Danio rerio | Structure: primordial germ cell Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Rap1 signaling pathway - Homo sapiens (human)
- Myometrial Relaxation and Contraction Pathways
- Calcium Regulation in the Cardiac Cell
- Signaling by GPCR
- Signal Transduction
Biological Process
- mitotic cell cycle
- nucleocytoplasmic transport
- response to oxidative stress
- spindle organization
- chromosome segregation
Molecular Function
- G-protein alpha-subunit binding
- GDP-dissociation inhibitor activity
- GTPase activator activity
- protein binding
- microtubule binding
Cellular Component
- spindle pole
- nucleus
- cytoplasm
- centrosome
- spindle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000408923
- Coding exons
- 15
- Length
- 14765
- Individuals with no LoFs
- 124781
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 124798
- p
- 0.0000681
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.545 | 309 | 337 | 0.917 | 0.0000194 | 3584 |
| Missense (PolyPhen) | 103 | 131.26 | 0.78468 | 1463 | ||
| Synonymous | 2.06 | 117 | 149 | 0.785 | 0.00000880 | 1193 |
| Loss of Function | 3.32 | 10 | 29.4 | 0.340 | 0.00000154 | 320 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.00024 | 0.00023 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o) alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)- mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal- based learning and memory. {ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:17635935}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.602
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.986
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |