MCPH1
Microcephalin 1, a key regulator of brain size and DNA damage response
Gene Information Card
| Symbol | MCPH1 |
|---|---|
| Full Name | Microcephalin 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 8p23.1 |
| NCBI Gene ID | 79648 ncbi.nlm.nih.gov/gene/79648 |
| Ensembl ID | ENSG00000147316 |
| UniProt ID | Q8NEM0 |
| OMIM ID | 607117 |
| HGNC ID | 6954 |
| Aliases | BRIT1, MCT, microcephalin |
Description
MCPH1 (microcephalin 1) encodes a protein involved in DNA damage response, chromosome condensation, and regulation of brain size. Mutations in this gene cause autosomal recessive primary microcephaly (MCPH1), characterized by reduced head circumference and intellectual disability. The protein contains three BRCT domains and localizes to the nucleus, where it interacts with key cell cycle regulators.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive primary microcephaly 1 (MCPH1) | Loss-of-function mutations impair DNA repair and cell cycle checkpoint control, leading to reduced neuronal proliferation | OMIM #251200; ClinVar pathogenic variants |
| Premature chromosome condensation syndrome | MCPH1 deficiency causes premature chromosome condensation in mitotic cells | PubMed; OMIM |
| Breast cancer susceptibility | MCPH1 (BRIT1) acts as a tumor suppressor; reduced expression linked to genomic instability | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Lymph node | 6.1 | Low |
| Bone marrow | 5.4 | Low |
| Ovary | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | Embryonic kidney cell line |
| HeLa | 10.7 | Cervical carcinoma cell line |
| MCF7 | 8.9 | Breast cancer cell line |
| U2OS | 12.1 | Osteosarcoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.428_429delCA (p.Thr143Argfs*5) | Frameshift | Rare | Loss of function; causes primary microcephaly |
| c.70C>T (p.Gln24*) | Nonsense | Rare | Premature stop; loss of function |
| c.940C>T (p.Arg314Trp) | Missense | Very rare | Impaired DNA damage response |
| c.1060C>T (p.Arg354Trp) | Missense | Rare | Reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Most MCPH1 mutations are loss-of-function, leading to truncated or unstable protein, impairing DNA repair and cell cycle control.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • signal transduction by p53 class mediator (GO:0030330) | • Chromosome condensation (GO:0030261) |
| • Centrosome cycle (GO:0007098) | • Protein binding (GO:0005515) |
| • Nucleus (GO:0005634) |
Pathways
• DNA damage response (ATM/ATR signaling)
• Cell cycle checkpoint control
• Chromosome condensation pathway
Protein Summary
The MCPH1 protein (microcephalin) is a 835-amino acid nuclear protein with three BRCT domains. It functions as a key regulator of DNA damage checkpoint signaling, promoting repair of double-strand breaks and maintaining genomic stability. It also facilitates chromosome condensation during mitosis. Loss of MCPH1 leads to microcephaly due to reduced neural progenitor proliferation and premature chromosome condensation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MCPH1 Knockout HEK293 Cell Line | EDJ-KQ1944 | Human | 79648 | Details Get a Quote |
| MCPH1 Knockout A-549 Cell Line | EDJ-KQ21881 | Human | 79648 | Details Get a Quote |
| MCPH1 Knockout HCT 116 Cell Line | EDJ-KQ21882 | Human | 79648 | Details Get a Quote |
| MCPH1 Knockout HeLa Cell Line | EDJ-KQ21883 | Human | 79648 | Details Get a Quote |
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