Muscular dystrophy, scapulohumeral

Summary

Muscular dystrophy, scapulohumeral (MONDO:0010884) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	muscular dystrophy, scapulohumeral
Mondo ID	MONDO:0010884
MeSH	C562932
OMIM	600416
SNOMED CT	240074006
UMLS	C0410192
MedGen	98373
GARD	0015317
Is cancer (heuristic)	no

Also known as: muscular dystrophy, scapulohumeral

Data availability: 12 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › facioscapulohumeral muscular dystrophy › muscular dystrophy, scapulohumeral

Related subtypes (4): facioscapulohumeral muscular dystrophy 1, facioscapulohumeral muscular dystrophy 2, facioscapulohumeral muscular dystrophy 3, digenic, facioscapulohumeral muscular dystrophy 4, digenic

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
689561	NM_015295.3(SMCHD1):c.4459C>T (p.Gln1487Ter)	SMCHD1	Pathogenic	no assertion criteria provided
291312	NM_015295.3(SMCHD1):c.1286ATC[1] (p.His430del)	SMCHD1	Likely pathogenic	no assertion criteria provided
446476	NM_015295.3(SMCHD1):c.3679G>C (p.Gly1227Arg)	SMCHD1	Likely pathogenic	no assertion criteria provided
637006	NM_015295.3(SMCHD1):c.4966+5G>A	SMCHD1	Likely pathogenic	no assertion criteria provided
689564	NM_015295.3(SMCHD1):c.790G>A (p.Glu264Lys)	SMCHD1	Likely pathogenic	no assertion criteria provided
286021	NM_015295.3(SMCHD1):c.3209T>C (p.Ile1070Thr)	SMCHD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
560349	NM_015295.3(SMCHD1):c.3529G>T (p.Asp1177Tyr)	SMCHD1	Uncertain significance	criteria provided, single submitter
560350	NM_015295.3(SMCHD1):c.2384T>C (p.Val795Ala)	SMCHD1	Uncertain significance	no assertion criteria provided
560357	NM_015295.3(SMCHD1):c.694A>G (p.Ile232Val)	SMCHD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
637007	NM_015295.3(SMCHD1):c.3097A>G (p.Ser1033Gly)	SMCHD1	Uncertain significance	no assertion criteria provided
689562	NM_015295.3(SMCHD1):c.89T>G (p.Leu30Trp)	SMCHD1	Uncertain significance	no assertion criteria provided
689563	NM_015295.3(SMCHD1):c.1172A>G (p.Asn391Ser)	SMCHD1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMCHD1	Orphanet:2250	Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome
SMCHD1	Orphanet:269	Facioscapulohumeral dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMCHD1	HGNC:29090	ENSG00000101596	A6NHR9	Structural maintenance of chromosomes flexible hinge domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMCHD1	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMCHD1	Other/Unknown	no		SMC_hinge, SMC_hinge_sf, HATPase_C_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
calcaneal tendon	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMCHD1	290	ubiquitous	marker	calcaneal tendon, colonic epithelium, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMCHD1	1,888

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMCHD1	A6NHR9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nose development	1	2407.4×	0.002	SMCHD1
autosome genomic imprinting	1	2407.4×	0.002	SMCHD1
dosage compensation by inactivation of X chromosome	1	1532.0×	0.002	SMCHD1
positive regulation of double-strand break repair via nonhomologous end joining	1	991.3×	0.002	SMCHD1
random inactivation of X chromosome	1	936.2×	0.002	SMCHD1
negative regulation of double-strand break repair via homologous recombination	1	624.1×	0.002	SMCHD1
chromosome organization	1	581.1×	0.002	SMCHD1
positive regulation of DNA repair	1	358.6×	0.003	SMCHD1
double-strand break repair	1	203.0×	0.005	SMCHD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMCHD1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMCHD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SMCHD1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SMCHD1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	SMCHD1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.