HRAS Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the HRAS gene, its protein product, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | HRAS |
|---|---|
| Full Name | HRas proto-oncogene, GTPase |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 3265 ncbi.nlm.nih.gov/gene/3265 |
| Ensembl ID | ENSG00000174775 |
| UniProt ID | P01112 |
| OMIM ID | 190020 |
| HGNC ID | 5173 |
| Aliases | C-H-RAS, H-RAS, HRAS1, RASH1, p21ras, c-Ha-ras |
Description
The HRAS gene encodes a membrane-bound protein, H-Ras, that functions as a molecular switch in signal transduction pathways. It is a member of the RAS superfamily of small GTPases. H-Ras cycles between an active GTP-bound state and an inactive GDP-bound state, regulating cell growth, differentiation, and survival. Activating mutations in HRAS are associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Costello Syndrome | Germline activating mutations (e.g., G12S, G12A) lead to constitutive activation of the RAS/MAPK pathway, causing developmental abnormalities. | OMIM, ClinVar |
| Bladder Cancer | Somatic activating mutations (e.g., G12V, G12D) drive uncontrolled cell proliferation and tumorigenesis. | COSMIC, ClinVar |
| Head and Neck Squamous Cell Carcinoma | Somatic activating mutations contribute to oncogenic signaling and tumor progression. | COSMIC, ClinVar |
| Rhabdomyosarcoma | Somatic activating mutations are found in a subset of tumors, promoting cell growth and survival. | COSMIC, ClinVar |
| Thyroid Carcinoma | Somatic activating mutations (e.g., Q61R) are implicated in follicular and papillary thyroid cancers. | COSMIC, ClinVar |
| Melanoma | Somatic activating mutations can drive tumorigenesis, though less frequent than in other cancers. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bladder | 8.2 | Medium |
| Kidney | 7.5 | Medium |
| Thyroid | 6.9 | Medium |
| Skin | 5.8 | Low |
| Lung | 4.5 | Low |
| Brain | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RT4 (Bladder) | 12.5 | High expression |
| A549 (Lung) | 8.1 | Medium expression |
| MCF7 (Breast) | 6.3 | Medium expression |
| HEK 293 (Embryonic Kidney) | 5.9 | Medium expression |
| K562 (Leukemia) | 2.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G12V | Missense | Common in bladder cancer | Constitutive activation, impaired GTP hydrolysis |
| G12D | Missense | Common in various cancers | Constitutive activation, impaired GTP hydrolysis |
| G12S | Missense | Common in Costello syndrome | Constitutive activation, impaired GTP hydrolysis |
| Q61R | Missense | Found in thyroid cancer and melanoma | Reduced intrinsic GTPase activity, constitutive activation |
| Q61K | Missense | Found in various cancers | Reduced intrinsic GTPase activity, constitutive activation |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in HRAS are rare and not well-characterized. Complete loss of HRAS function is likely compensated by other RAS family members (KRAS, NRAS) and is not a primary driver of disease.
Gain of Function (GOF)
The vast majority of pathogenic HRAS mutations are gain-of-function. These are typically missense mutations at codons 12, 13, or 61 that impair the intrinsic GTPase activity or promote GDP/GTP exchange, leading to constitutive activation of downstream signaling pathways.
Dominant Negative (DN)
Dominant-negative HRAS mutations are uncommon. Some experimental mutants can sequester guanine nucleotide exchange factors (GEFs), preventing activation of wild-type RAS proteins, but these are not typically found in human diseases.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • GDP binding | • Protein binding |
| • Signal transduction | • Cell proliferation |
| • Regulation of cell growth | • Ras protein signal transduction |
Pathways
• MAPK/ERK signaling pathway
• PI3K/AKT signaling pathway
• Ras signaling pathway
• Rap1 signaling pathway
• Regulation of actin cytoskeleton
Protein Summary
The H-Ras protein is a 21 kDa membrane-associated GTPase that acts as a molecular switch. It is anchored to the plasma membrane via a C-terminal farnesyl group. In its active GTP-bound state, H-Ras interacts with and activates downstream effectors such as RAF kinases and PI3K, leading to cell proliferation and survival. The intrinsic GTPase activity of H-Ras is stimulated by GTPase-activating proteins (GAPs), while guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP. Mutations that disrupt this cycle lead to constitutive signaling and oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HRAS Knockout HEK293 Cell Line | EDJ-KQ467 | Human | 3265 | Details Get a Quote |
| HRAS Knockout A-549 Cell Line | EDJ-KQ18774 | Human | 3265 | Details Get a Quote |
| HRAS Knockout HCT 116 Cell Line | EDJ-KQ18775 | Human | 3265 | Details Get a Quote |
| HRAS Knockout HeLa Cell Line | EDJ-KQ18776 | Human | 3265 | Details Get a Quote |
| HRAS (p.Q61K) Point Mutation in HCT 116 Cell Line | EDC03105 | Human | 3265 | Details Get a Quote |
| HRAS (p.G13R) Point Mutation in HCT 116 Cell Line | EDC03111 | Human | 3265 | Details Get a Quote |
| HRAS (p.Q61R) Point Mutation in HCT 116 Cell Line | EDC03081 | Human | 3265 | Details Get a Quote |
| HRAS (p.G12V) Point Mutation in HCT 116 Cell Line | EDC03113 | Human | 3265 | Details Get a Quote |
| HRAS (p.G12D) Point Mutation in HCT 116 Cell Line | EDC03112 | Human | 3265 | Details Get a Quote |
| HRAS (p.G161R) Point Mutation in HAP1 Cell Line | EDC03508 | Human | 3265 | Details Get a Quote |
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