TRIM37 Gene: E3 Ubiquitin Ligase, Mulibrey Nanism, and Cancer Susceptibility
Explore the TRIM37 gene, its protein function, associated diseases like Mulibrey Nanism, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | TRIM37 |
|---|---|
| Full Name | Tripartite Motif Containing 37 |
| Gene Type | Protein coding |
| Chromosomal Location | Chromosome 17 (17q22) |
| NCBI Gene ID | 4591 ncbi.nlm.nih.gov/gene/4591 |
| Ensembl ID | ENSG00000108379 |
| UniProt ID | O94972 |
| OMIM ID | 605073 |
| HGNC ID | 7523 |
| Aliases | MUL, POB1, TEF1 |
Description
The TRIM37 gene encodes a member of the tripartite motif (TRIM) family of proteins. TRIM37 functions as an E3 ubiquitin-protein ligase, playing a critical role in various cellular processes including protein degradation, transcriptional regulation, and DNA damage response. It is localized to peroxisomes and is involved in the ubiquitination of specific substrates. Mutations in this gene are the cause of Mulibrey Nanism (MUL), a rare autosomal recessive growth disorder. Additionally, TRIM37 has been implicated in oncogenesis, particularly in breast cancer, where its overexpression can promote tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mulibrey Nanism (MUL) | Loss-of-function mutations in TRIM37 lead to a deficiency in E3 ubiquitin ligase activity, disrupting normal peroxisomal function and cellular growth regulation, resulting in the characteristic features of the disorder. | OMIM: 605073; ClinVar |
| Breast Cancer | Overexpression and amplification of TRIM37 have been observed in breast cancer, particularly in certain subtypes. It can promote tumorigenesis by ubiquitinating and degrading tumor suppressor proteins like p53, thereby enhancing cell proliferation and survival. | COSMIC; PubMed (multiple studies) |
| Neuroblastoma | TRIM37 expression has been linked to neuroblastoma pathogenesis, where it may contribute to tumor progression through similar mechanisms as in breast cancer, though the exact role is still under investigation. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 22.5 | Medium |
| Kidney | 18.3 | Medium |
| Liver | 15.1 | Medium |
| Lung | 12.8 | Low |
| Brain | 8.5 | Low |
| Heart | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (Breast Cancer) | 25.4 | High expression; consistent with its role in breast cancer |
| A549 (Lung Cancer) | 15.2 | Moderate expression |
| HepG2 (Liver Cancer) | 18.7 | Moderate expression |
| K562 (Leukemia) | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.493-2A>G | Splice site | Reported in Mulibrey Nanism patients | Splice acceptor site mutation leading to aberrant splicing and loss of functional protein. |
| p.Arg487* | Nonsense | Reported in Mulibrey Nanism patients | Premature stop codon resulting in a truncated, non-functional protein. |
| p.Gly120Asp | Missense | Reported in Mulibrey Nanism patients | Amino acid substitution in the RING finger domain, likely disrupting E3 ligase activity. |
| Gene Amplification | Copy Number Gain | Observed in breast cancer cell lines and tumors | Increased gene copy number leads to TRIM37 overexpression, promoting tumorigenesis. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, including nonsense, frameshift, and splice-site variants, are the primary cause of Mulibrey Nanism. These mutations result in a non-functional or absent TRIM37 protein, leading to the characteristic developmental and growth defects.
Gain of Function (GOF)
Gain-of-function is primarily observed in cancer through gene amplification and transcriptional overexpression. This leads to increased E3 ligase activity, promoting degradation of tumor suppressors and enhancing oncogenic signaling.
Dominant Negative (DN)
While not a classic mechanism for TRIM37, certain missense mutations could potentially exert a dominant-negative effect by forming non-functional dimers with the wild-type protein, though this is not well-established for this gene.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin-Proteasome Pathway
• p53 Signaling Pathway (via ubiquitination of p53)
• DNA Damage Response
Protein Summary
The TRIM37 protein is a 964-amino acid E3 ubiquitin ligase belonging to the TRIM family. It contains a RING finger domain, B-box domains, and a coiled-coil region, which are characteristic of this family. The protein localizes to peroxisomes and functions in ubiquitinating specific protein substrates, targeting them for proteasomal degradation. It plays a role in regulating cell growth, differentiation, and genomic stability. Dysregulation of TRIM37, either through loss-of-function mutations or overexpression, contributes to developmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIM37 Knockout HEK293 Cell Line | EDJ-KQ3188 | Human | 4591 | Details Get a Quote |
| TRIM37 Knockout A-549 Cell Line | EDJ-KQ24628 | Human | 4591 | Details Get a Quote |
| TRIM37 Knockout HCT 116 Cell Line | EDJ-KQ24629 | Human | 4591 | Details Get a Quote |
| TRIM37 Knockout HeLa Cell Line | EDJ-KQ24630 | Human | 4591 | Details Get a Quote |
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