RHOH Gene - Rho GTPase Family Member H
Atypical Rho GTPase Involved in Hematopoietic Cell Signaling and Immune Function
Gene Information Card
| Symbol | RHOH |
|---|---|
| Full Name | Ras Homolog Family Member H |
| Gene Type | protein-coding |
| Chromosomal Location | 4p14 |
| NCBI Gene ID | 399 ncbi.nlm.nih.gov/gene/399 |
| Ensembl ID | ENSG00000168421 |
| UniProt ID | Q15669 |
| OMIM ID | 602853 |
| HGNC ID | 10001 |
| Aliases | ARHH, TTF, RhoH, Rho-6 |
Description
RHOH (Ras Homolog Family Member H) encodes a member of the Rho family of small GTPases. Unlike classical Rho proteins, RHOH is GTPase-deficient and constitutively active. It is predominantly expressed in hematopoietic cells and plays a critical role in T-cell receptor signaling, cell adhesion, and migration. RHOH functions as a negative regulator of hematopoietic cell proliferation and is implicated in immune system development and cancer, particularly T-cell lymphomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Peripheral T-cell lymphoma (PTCL) | RHOH mutations lead to aberrant T-cell signaling and proliferation, contributing to lymphomagenesis. | PMID: 24681948; COSMIC |
| Angioimmunoblastic T-cell lymphoma (AITL) | Recurrent RHOH mutations impair RHOH-mediated negative regulation of T-cell activation, promoting clonal expansion. | PMID: 24681948; COSMIC |
| Severe combined immunodeficiency (SCID) | Loss-of-function RHOH mutations disrupt T-cell development and function, causing immunodeficiency. | PMID: 22461475; ClinVar |
| Hodgkin lymphoma | RHOH downregulation or mutation may contribute to aberrant signaling in Hodgkin Reed-Sternberg cells. | PMID: 23033268; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Medium |
| Thymus | 7.9 | Medium |
| Blood | 6.5 | Low |
| Lung | 1.2 | Not detected |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.3 | High expression; model for T-cell signaling |
| Raji (Burkitt lymphoma) | 9.1 | Moderate expression |
| K562 (chronic myeloid leukemia) | 7.4 | Moderate expression |
| HEK293 (embryonic kidney) | 0.5 | Very low; not hematopoietic origin |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.64C>T (p.Arg22*) | Nonsense | <1% | Loss of function; truncation; associated with SCID |
| c.277G>A (p.Gly93Arg) | Missense | <1% | Loss of function; impaired GTP binding; found in PTCL |
| c.346C>T (p.Arg116Trp) | Missense | <1% | Gain of function?; altered signaling; reported in AITL |
| c.421_422del (p.Leu141fs) | Frameshift | <1% | Loss of function; truncation; immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that disrupt RHOH protein expression or GTP-binding ability lead to loss of negative regulation in T-cell signaling, contributing to immunodeficiency or lymphoma.
Gain of Function (GOF)
Some missense mutations (e.g., p.Arg116Trp) may alter RHOH interaction partners, potentially enhancing oncogenic signaling, though evidence is limited.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; RHOH typically acts as a haploinsufficient tumor suppressor.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • Protein binding | • Signal transduction |
| • Cell adhesion | • Negative regulation of T-cell receptor signaling pathway |
| • Positive regulation of cell migration | • Intracellular signal transduction |
Pathways
• Rho GTPase cycle (Reactome: R-HSA-194840)
• T-cell receptor signaling pathway (KEGG: hsa04660)
• Chemokine signaling pathway (KEGG: hsa04062)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
Protein Summary
RHOH is a 191-amino acid atypical Rho GTPase that lacks intrinsic GTPase activity, rendering it constitutively active. It is predominantly expressed in hematopoietic cells and localizes to the plasma membrane and cytoplasm. RHOH negatively regulates T-cell receptor signaling by competing with other Rho GTPases for effector binding and modulating actin dynamics. It also influences cell adhesion and migration. Loss of RHOH function is associated with T-cell lymphomas and primary immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RHOH Knockout HEK293 Cell Line | EDJ-KQ4090 | Human | 399 | Details Get a Quote |
| RHOH Knockout HeLa Cell Line | EDJ-KQ52659 | Human | 399 | Details Get a Quote |
| RHOH Knockout A-549 Cell Line | EDJ-KQ61132 | Human | 399 | Details Get a Quote |
| RHOH Knockout HCT 116 Cell Line | EDJ-KQ69619 | Human | 399 | Details Get a Quote |
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