SMCHD1: Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1
A chromatin regulator implicated in facioscapulohumeral muscular dystrophy (FSHD), Bosma arhinia microphthalmia syndrome (BAMS), and epigenetic gene silencing.
Gene Information Card
| Symbol | SMCHD1 |
|---|---|
| Full Name | Structural maintenance of chromosomes flexible hinge domain containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 18p11.32 |
| NCBI Gene ID | 23347 ncbi.nlm.nih.gov/gene/23347 |
| Ensembl ID | ENSG00000146094 |
| UniProt ID | Q6P3V7 |
| OMIM ID | 614982 |
| HGNC ID | 29090 |
| Aliases | FSHD2, BAMS, D4Z4-binding protein, KIAA1950 |
Description
SMCHD1 encodes a protein that belongs to the structural maintenance of chromosomes (SMC) family, but it lacks the ATPase domain typical of canonical SMC proteins. It functions as a chromatin regulator that mediates epigenetic silencing through DNA methylation and histone modifications. SMCHD1 is critical for X-chromosome inactivation, imprinting, and repression of repetitive elements such as the D4Z4 macrosatellite repeat on chromosome 4. Mutations in SMCHD1 are associated with facioscapulohumeral muscular dystrophy type 2 (FSHD2) and Bosma arhinia microphthalmia syndrome (BAMS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Facioscapulohumeral muscular dystrophy 2 (FSHD2) | Loss-of-function mutations in SMCHD1 reduce D4Z4 methylation, leading to derepression of the DUX4 retrogene in muscle cells, causing toxicity. | ClinVar, OMIM |
| Bosma arhinia microphthalmia syndrome (BAMS) | Missense mutations in SMCHD1 disrupt its chromatin-binding function, affecting craniofacial development, though the exact mechanism is not fully understood. | OMIM, PubMed |
| Congenital arhinia | Similar to BAMS, SMCHD1 mutations cause nasal and eye malformations, likely due to altered gene expression during development. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Muscle | 10.2 | Medium |
| Brain | 8.5 | Medium |
| Testis | 7.8 | Medium |
| Lung | 6.4 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.3 | Cervical cancer cell line |
| K562 | 9.8 | Leukemia cell line |
| A549 | 7.2 | Lung carcinoma cell line |
| GM12878 | 11.5 | Lymphoblastoid cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2885C>T (p.Pro962Leu) | Missense | Rare | Associated with BAMS; disrupts protein function. |
| c.1045C>T (p.Arg349Ter) | Nonsense | Rare | Loss-of-function; causes FSHD2. |
| c.1910G>A (p.Arg637His) | Missense | Rare | Likely pathogenic; BAMS. |
| c.2260delA (p.Thr754ProfsTer23) | Frameshift | Rare | Loss-of-function; FSHD2. |
Mutation functional classification
Loss of Function (LOF)
Most FSHD2-associated mutations are loss-of-function, leading to reduced D4Z4 methylation and DUX4 derepression.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some BAMS mutations may have dominant-negative effects.
Dominant Negative (DN)
Some missense mutations in BAMS may act in a dominant-negative manner, interfering with wild-type SMCHD1 function.
View complete mutation data：
Gene Ontology (GO)
| • chromatin binding | • DNA binding |
| • methylated histone binding | • protein homodimerization activity |
| • chromatin organization | • gene silencing |
| • X-inactivation | • DNA methylation |
Pathways
• Epigenetic regulation of gene expression
• X chromosome inactivation
• D4Z4 repeat silencing
Protein Summary
SMCHD1 is a 2005-amino-acid protein with an N-terminal SMC hinge domain and a C-terminal GHKL ATPase-like domain (though catalytically inactive). It forms homodimers and binds to chromatin, recruiting DNA methyltransferases to establish and maintain methylation at specific loci. It plays a key role in silencing repetitive elements and imprinted genes. Mutations lead to epigenetic dysregulation, causing FSHD2 and BAMS.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMCHD1 Knockout HEK293 Cell Line | EDJ-KQ7980 | Human | 23347 | Details Get a Quote |
| SMCHD1 Knockout A-549 Cell Line | EDJ-KQ33690 | Human | 23347 | Details Get a Quote |
| SMCHD1 Knockout HCT 116 Cell Line | EDJ-KQ33691 | Human | 23347 | Details Get a Quote |
| SMCHD1 Knockout HeLa Cell Line | EDJ-KQ33692 | Human | 23347 | Details Get a Quote |
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