TMEM147: Transmembrane Protein 147 – A Key Regulator of Nuclear Envelope and Neurological Disorders
Comprehensive genomic and proteomic analysis of TMEM147, its role in nuclear envelope integrity, and association with intellectual disability and dystonia.
Gene Information Card
| Symbol | TMEM147 |
|---|---|
| Full Name | Transmembrane Protein 147 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 10430 ncbi.nlm.nih.gov/gene/10430 |
| Ensembl ID | ENSG00000105669 |
| UniProt ID | Q9BVK8 |
| OMIM ID | 619422 |
| HGNC ID | 30414 |
| Aliases | DC11, NIFIE14, TMEM147-AS1 |
Description
TMEM147 encodes a multi-pass transmembrane protein localized to the nuclear envelope and endoplasmic reticulum. It is involved in nuclear membrane integrity, protein trafficking, and calcium homeostasis. Mutations in TMEM147 cause autosomal recessive intellectual disability with dystonia and other neurological features. The protein interacts with the nuclear pore complex and is essential for proper neuronal development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder with dystonia (IDDYS) | Loss-of-function mutations impair nuclear envelope integrity, leading to neuronal dysfunction | OMIM #619422; ClinVar pathogenic variants |
| Dystonia | Disrupted calcium signaling and nuclear pore complex function | ClinVar; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Testis | 8.3 | Low |
| Kidney | 7.1 | Low |
| Liver | 5.9 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 10.1 | Common expression system |
| HeLa (cervical carcinoma) | 9.5 | Epithelial model |
| HepG2 (hepatocellular carcinoma) | 6.3 | Liver model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense/Start loss | Rare | Loss of protein expression |
| c.202C>T (p.Arg68Trp) | Missense | Rare | Impaired nuclear envelope localization |
| c.344G>A (p.Arg115His) | Missense | Rare | Reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Pathogenic missense and start-loss variants lead to reduced protein levels or mislocalization, causing autosomal recessive intellectual disability with dystonia.
Gain of Function (GOF)
No evidence of gain-of-function mutations reported.
Dominant Negative (DN)
No evidence of dominant-negative effects; disease inheritance is recessive.
View complete mutation data：
Gene Ontology (GO)
| • nuclear envelope (GO:0005635) | • endoplasmic reticulum (GO:0005783) |
| • integral component of membrane (GO:0016021) | • calcium ion transport (GO:0006816) |
| • neuronal cell body (GO:0043025) |
Pathways
• Nuclear envelope integrity and nuclear pore complex assembly
• Calcium signaling pathway
Protein Summary
TMEM147 is a 147-amino acid transmembrane protein with four predicted membrane-spanning domains. It resides primarily in the nuclear envelope and endoplasmic reticulum, where it contributes to membrane curvature and nuclear pore complex organization. The protein is highly conserved in vertebrates and is essential for normal neuronal function. Loss of TMEM147 disrupts nuclear morphology and calcium homeostasis, leading to neurological disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM147 Knockout HEK293 Cell Line | EDJ-KQ3015 | Human | 10430 | Details Get a Quote |
| TMEM147 Knockout A-549 Cell Line | EDJ-KQ25603 | Human | 10430 | Details Get a Quote |
| TMEM147 Knockout HCT 116 Cell Line | EDJ-KQ25604 | Human | 10430 | Details Get a Quote |
| TMEM147 Knockout HeLa Cell Line | EDJ-KQ25605 | Human | 10430 | Details Get a Quote |
