RIC8A
protein-codingRIC8 guanine nucleotide exchange factor A, the group of Armadillo like helical domain containing|MicroRNA protein coding host genes
Gene summary
Predicted to enable G-protein alpha-subunit binding activity; GTPase regulator activity; and protein folding chaperone. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including basement membrane organization; gastrulation; and visual learning. Predicted to be located in cell cortex and membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.4 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 RIC8A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001286134.2. 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 | 1 | 1 | ||||
| missense | 87 | 5 | 92 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 89 | 6 | 0 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001273063.1 | 10 | MANE Select | |
| Ensembl | ENSP00000432008.1 | 10 | MANE Select | |
| RefSeq | NP_001373870.1 | 10 | Standard | |
| RefSeq | NP_001373871.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- in utero embryonic development
- vasculature development
- G protein-coupled receptor signaling pathway
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- visual learning
Molecular Function
- G-protein alpha-subunit binding
- guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
Cellular Component
- cytoplasm
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000325207
- Coding exons
- 10
- Length
- 7603
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.827 | 294 | 337 | 0.873 | 0.0000205 | 3473 |
| Missense (PolyPhen) | 106 | 124.6 | 0.85072 | 1293 | ||
| Synonymous | 0.366 | 132 | 137 | 0.960 | 0.00000797 | 1127 |
| Loss of Function | 2.51 | 9 | 21.6 | 0.417 | 0.00000118 | 241 |
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 | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000090 | 0.000088 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein, possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex (By similarity). Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation. {ECO:0000250, ECO:0000269|PubMed:16629901}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.428
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.769
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |