RHOC
protein-codingras homolog family member C, the group of Rho family GTPases
Gene summary
This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The protein encoded by this gene is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
- ARH9
- ARHC
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.3 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 RHOC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_175744.5. 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 | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 18 | 0 | 0 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_786886.1 | 4 | MANE Select | |
| Ensembl | ENSP00000345236.8 | 4 | MANE Select | |
| RefSeq | NP_001036143.1 | 4 | Standard | |
| RefSeq | NP_001036144.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spinal Cord Injury
- VEGFA-VEGFR2 Signaling Pathway
- Ebola Virus Pathway on Host
- Ebola Virus Pathway on Host
- Developmental Biology
Biological Process
- mitotic cytokinesis
- actin filament organization
- G protein-coupled receptor signaling pathway
- Rho protein signal transduction
- regulation of cell shape
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- protein kinase binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
- cell cortex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000285735
- Coding exons
- 4
- Length
- 6329
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125745
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.85 | 65 | 123 | 0.530 | 0.00000787 | 1260 |
| Missense (PolyPhen) | 15 | 33.874 | 0.44282 | 424 | ||
| Synonymous | -1.13 | 58 | 48.0 | 1.21 | 0.00000300 | 378 |
| Loss of Function | 2.50 | 1 | 9.17 | 0.109 | 5.38e-7 | 96 |
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 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells. {ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:20974804}.;
Recessive Scores
- pRec
- 0.188
Intolerance Scores
- LoFtool
- 0.309
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |