RASSF5 (Ras Association Domain Family Member 5)
A multifunctional adaptor protein involved in growth control, apoptosis, and immune cell signaling, with implications in cancer and development.
Gene Information Card
| Symbol | RASSF5 |
|---|---|
| Full Name | Ras association domain family member 5 |
| Gene Type | protein coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 8359 ncbi.nlm.nih.gov/gene/8359 |
| Ensembl ID | ENSG00000136628 |
| UniProt ID | Q8WWW0 |
| OMIM ID | 607020 |
| HGNC ID | 17607 |
| Aliases | NORE1, RAPL, NORE1A, NORE1B, RASSF5A, RASSF5B |
Description
RASSF5 (Ras association domain family member 5) encodes a protein that belongs to the Ras association domain family. It functions as an adaptor protein that interacts with Ras family GTPases, regulating cell proliferation, apoptosis, and immune cell signaling. RASSF5 has two major isoforms (RASSF5A/NORE1A and RASSF5B/RAPL) with distinct functions. It acts as a tumor suppressor in various cancers, and is also involved in lymphocyte polarization and integrin activation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Loss of RASSF5 expression or function leads to deregulated cell growth and survival, contributing to tumorigenesis. | Multiple studies show promoter methylation and reduced expression in various cancers (e.g., lung, breast, colorectal). |
| Immune deficiency | RASSF5B (RAPL) is essential for lymphocyte adhesion and migration; defects may impair immune responses. | Mouse models with RASSF5 knockout show defective T-cell homing and immune synapse formation. |
| Developmental disorders | RASSF5 may influence neuronal development and survival; mutations could contribute to neurodevelopmental phenotypes. | Limited evidence; further research needed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Spleen | 10.8 | Medium |
| Thymus | 9.5 | Medium |
| Brain | 7.2 | Low |
| Heart | 5.1 | Low |
| Liver | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 15.2 | Moderate expression |
| MCF7 (Breast carcinoma) | 8.7 | Low expression |
| HEK293 (Embryonic kidney) | 12.0 | Moderate expression |
| Jurkat (T-cell leukemia) | 18.5 | High expression |
| HeLa (Cervical carcinoma) | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.637C>T (p.Arg213Ter) | Nonsense | Rare (<0.1%) | Truncated protein, likely loss of function |
| c.1105A>G (p.Ile369Val) | Missense | 0.2% | Unknown; may affect protein stability |
| c.148C>T (p.Arg50Cys) | Missense | 0.1% | Potential impact on Ras binding |
| Promoter methylation | Epigenetic | Frequent in tumors | Silencing of gene expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that lead to truncated proteins or promoter methylation causing gene silencing are classified as loss-of-function, contributing to tumor suppressor inactivation.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; RASSF5 is primarily a tumor suppressor, and activating mutations are not common.
Dominant Negative (DN)
Some missense mutations in the Ras association domain may produce proteins that compete with wild-type RASSF5 for binding partners, potentially acting in a dominant-negative manner, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • metal ion binding |
| • signal transducer activity | • apoptotic process |
| • cell proliferation | • cell adhesion |
| • immune response | • Ras protein signal transduction |
Pathways
• Ras signaling pathway
• Apoptosis
• T-cell receptor signaling pathway
• Integrin signaling pathway
• Hippo signaling pathway
Protein Summary
The RASSF5 protein is a modular adaptor with a Ras association (RA) domain, a Salvador/RASSF/Hippo (SARAH) domain, and a coiled-coil region. Isoform A (NORE1A) interacts with Ras and MST1/2 to promote apoptosis and growth suppression. Isoform B (RAPL) regulates lymphocyte polarization and integrin-mediated adhesion. The protein is widely expressed, with highest levels in immune tissues. Loss of RASSF5 expression is common in cancers due to promoter methylation, highlighting its role as a tumor suppressor.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASSF5 Knockout HEK293 Cell Line | EDJ-KQ1234 | Human | 83593 | Details Get a Quote |
| RASSF5 Knockout A-549 Cell Line | EDJ-KQ20581 | Human | 83593 | Details Get a Quote |
| RASSF5 Knockout HCT 116 Cell Line | EDJ-KQ20582 | Human | 83593 | Details Get a Quote |
| RASSF5 Knockout HeLa Cell Line | EDJ-KQ20583 | Human | 83593 | Details Get a Quote |
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