SMCHD1

Chr 18p11.32

structural maintenance of chromosomes flexible hinge domain containing 1

Aliases:: KIAA0650, FSHD2
MANE:: ENST00000320876.11

OMIM: 614982 ↗NCBI: 23347 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

SMCHD1 · A6NHR9

v62025-08-01

Predicted Aligned Error matrix for SMCHD1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

80.8/ 100

Confident

2,005 residues

Confidence breakdown

Very high(≥ 90)20%
Confident(70–90)68%
Low(50–70)8%
Very low(< 50)5%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Facioscapulohumeral muscular dystrophy - extended testing
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis
Congenital muscular dystrophy
Other
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

facioscapulohumeral muscular dystrophy 2
0.81
Facioscapulohumeral dystrophy
0.78
arhinia, choanal atresia, and microphthalmia
0.77
Hyposmia - nasal and ocular hypoplasia - hypogonadotropic hypogonadism
0.69
Arrhinia - choanal atresia - microphthalmia
0.67
neurodegenerative disease
0.49
hereditary disease
0.47
Scapulohumeral muscular dystrophy
0.47
Abnormality of the musculature
0.43
Anosmia
0.42

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Structural maintenance of chromosomes flexible hinge domain-containing protein 1

Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture (By similarity). Promotes heterochromatin formation in both autosomes and chromosome X, probably by mediating the merge of chromatin compartments (By similarity). Plays a key role in chromosome X inactivation in females by promoting the spreading of heterochromatin (PubMed:23542155). Recruited to inactivated chromosome X by Xist RNA and acts by mediating the merge of chromatin compartments: promotes random chromatin interactions that span the boundaries of existing structures, leading to create a compartment-less architecture typical of inactivated chromosome X (By similarity). Required to facilitate Xist RNA spreading (By similarity). Also required for silencing of a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus (PubMed:23143600). Has ATPase activity; may participate in structural manipulation of chromatin in an ATP-dependent manner as part of its role in gene expression regulation (PubMed:29748383). Also plays a role in DNA repair: localizes to sites of DNA double-strand breaks in response to DNA damage to promote the repair of DNA double-strand breaks (PubMed:24790221, PubMed:25294876). Acts by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination (HR) repair (PubMed:25294876)