TENM4: Teneurin Transmembrane Protein 4
A key gene in neurodevelopment, oligodendrocyte differentiation, and genetic susceptibility to bipolar disorder and multiple sclerosis.
Gene Information Card
| Symbol | TENM4 |
|---|---|
| Full Name | Teneurin Transmembrane Protein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q14.1 |
| NCBI Gene ID | 26011 ncbi.nlm.nih.gov/gene/26011 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q6N022 |
| OMIM ID | 610084 |
| HGNC ID | 29945 |
| Aliases | ODZ4, KIAA1302, TEN-M4, DOC4 |
Description
TENM4 encodes teneurin-4, a transmembrane glycoprotein involved in neuronal development, axon guidance, and oligodendrocyte differentiation. It belongs to the teneurin family of cell adhesion molecules. The protein contains a large extracellular domain with EGF-like repeats and a G protein-coupled receptor (GPCR) proteolysis site. TENM4 is highly expressed in the brain and has been implicated in bipolar disorder, multiple sclerosis, and spermatogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bipolar disorder | Genetic association; risk variant in intronic region | GWAS (PMID: 21926972, 31043756) |
| Multiple sclerosis | Altered oligodendrocyte differentiation and myelination | GWAS (PMID: 21833088, 24076602) |
| Autism spectrum disorder | De novo missense variants affecting protein function | Exome sequencing (PMID: 22495306) |
| Spermatogenic failure | Homozygous loss-of-function mutations impair sperm motility | Case study (PMID: 28166811) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Cerebellum | 10.8 | Medium |
| Testis | 8.2 | Medium |
| Spinal cord | 7.1 | Low |
| Heart | 2.3 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | Neuronal model |
| U-87 MG (glioblastoma) | 9.8 | Glial model |
| HEK 293 (embryonic kidney) | 1.1 | Low endogenous expression |
| HepG2 (hepatocellular carcinoma) | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2875C>T (p.Arg959Cys) | Missense | <0.01% | Decreased cell surface expression; autism-associated |
| c.4420G>A (p.Gly1474Arg) | Missense | <0.01% | Impaired oligodendrocyte differentiation; MS risk |
| c.1234delC (p.Leu412Trpfs*3) | Frameshift | Rare | Loss of function; spermatogenic failure |
| rs12553324 (intronic) | SNP | 0.15 (MAF) | Bipolar disorder risk allele |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Leu412Trpfs*3) lead to truncated protein and loss of teneurin-4 function, associated with spermatogenic failure.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TENM4.
Dominant Negative (DN)
Missense variants (e.g., p.Arg959Cys) may exert dominant-negative effects by disrupting dimerization or cell surface localization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Teneurin signaling pathway (Reactome: R-HSA-8848021)
• Cell adhesion molecules (CAMs) (KEGG: hsa04514)
• GPCR ligand binding (Reactome: R-HSA-500792)
Protein Summary
Teneurin-4 (TENM4) is a 2,735-amino-acid transmembrane protein with a large N-terminal extracellular domain containing eight EGF-like repeats and a C-terminal intracellular domain. It forms homodimers and mediates cell-cell adhesion. The protein undergoes proteolytic cleavage at the GPCR proteolysis site, releasing an extracellular fragment that may act as a signaling molecule. TENM4 is essential for proper myelination and neuronal connectivity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TENM4 Knockout HEK293 Cell Line | EDJ-KQ2051 | Human | 26011 | Details Get a Quote |
| TENM4 Knockout HeLa Cell Line | EDJ-KQ55864 | Human | 26011 | Details Get a Quote |
| TENM4 Knockout A-549 Cell Line | EDJ-KQ64355 | Human | 26011 | Details Get a Quote |
| TENM4 Knockout HCT 116 Cell Line | EDJ-KQ72804 | Human | 26011 | Details Get a Quote |
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