RHOD
protein-codingras homolog family member D, the group of Rho family GTPases
Gene summary
Ras homolog, or Rho, proteins interact with protein kinases and may serve as targets for activated GTPase. They play a critical role in muscle differentiation. The protein encoded by this gene binds GTP and is a member of the small GTPase superfamily. It is involved in endosome dynamics and reorganization of the actin cytoskeleton, and it may coordinate membrane transport with the function of the cytoskeleton. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
- ARHD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.2 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 RHOD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014578.4. 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 | 2 | 1 | 3 | |||
| missense | 24 | 24 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 27 | 0 | 1 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055393.1 | 5 | MANE Select | |
| Ensembl | ENSP00000308576.2 | 5 | MANE Select | |
| RefSeq | NP_001287815.1 | 3 | Standard | |
| Ensembl | ENSP00000432003.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Signal Transduction
- RHO GTPases Activate Formins
- Rho GTPase cycle
- RHO GTPase Effectors
Biological Process
- protein targeting
- actin filament organization
- Rho protein signal transduction
- regulation of cell shape
- cell migration
Molecular Function
- GTPase activity
- GTP binding
- protein kinase binding
Cellular Component
- cytoplasm
- early endosome
- cytosol
- plasma membrane
- cell cortex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308831
- Coding exons
- 5
- Length
- 15196
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 25
- Defined
- 125748
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.939 | 95 | 124 | 0.763 | 0.00000778 | 1337 |
| Missense (PolyPhen) | 41 | 56.249 | 0.72891 | 579 | ||
| Synonymous | 1.33 | 43 | 55.6 | 0.773 | 0.00000372 | 421 |
| Loss of Function | 1.41 | 4 | 8.42 | 0.475 | 4.43e-7 | 94 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00022 | 0.00019 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in endosome dynamics. May coordinate membrane transport with the function of the cytoskeleton. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Participates in the reorganization of actin cytoskeleton; the function seems to involve WHAMM and includes regulation of filopodia formation and actin filament bundling. Can modulate the effect of DAPK3 in reorganization of actin cytoskeleton and focal adhesion dissolution. {ECO:0000269|PubMed:23087206, ECO:0000269|PubMed:23454120, ECO:0000269|PubMed:24102721}.;
Recessive Scores
- pRec
- 0.207
Intolerance Scores
- LoFtool
- 0.592
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.487
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |