X-linked scapuloperoneal muscular dystrophy

Summary

X-linked scapuloperoneal muscular dystrophy (MONDO:0010400) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		22	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked scapuloperoneal muscular dystrophy
Mondo ID	MONDO:0010400
OMIM	300695
Orphanet	431272
UMLS	C2678061
MedGen	395530
GARD	0007608
Is cancer (heuristic)	no

Also known as: scapuloperoneal myopathy, X-linked dominant · scapuloperoneal myopathy, X-linked dominant, X-linked dominant · SPM · X-linked scapuloperoneal syndrome · X-linked SPMD

Data availability: 29 ClinVar variants · 1 GenCC gene-disease record · 2 cell lines.

Disease family

Classification path: human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › Emery-Dreifuss muscular dystrophy › scapuloperoneal myopathy › X-linked scapuloperoneal muscular dystrophy

Related subtypes (1): congenital myopathy 7A, myosin storage, autosomal dominant

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

29 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 3 pathogenic, 3 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 benign, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074316	NM_001159699.2(FHL1):c.590G>A (p.Trp197Ter)	FHL1	Pathogenic	criteria provided, multiple submitters, no conflicts
11547	NM_001159699.2(FHL1):c.413G>C (p.Trp138Ser)	FHL1	Pathogenic	criteria provided, multiple submitters, no conflicts
11549	NM_001159699.2(FHL1):c.428_430dup (p.Phe143_Thr144insIle)	FHL1	Pathogenic	no assertion criteria provided
689729	NM_001159699.2(FHL1):c.496T>C (p.Cys166Arg)	FHL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3362611	NM_001159702.3(FHL1):c.705_706del (p.Arg236fs)	FHL1	Likely pathogenic	criteria provided, single submitter
3896865	NM_001159699.2(FHL1):c.350G>T (p.Cys117Phe)	FHL1	Likely pathogenic	criteria provided, single submitter
597908	NM_001159699.2(FHL1):c.785_793dup (p.Tyr264_Cys265insTyrAspTyr)	FHL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
838581	NM_001159699.2(FHL1):c.239C>A (p.Thr80Asn)	FHL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
944147	NM_001159699.2(FHL1):c.810dup (p.Cys271fs)	FHL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1016186	NM_001159699.2(FHL1):c.480A>C (p.Lys160Asn)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1057575	NM_001159699.2(FHL1):c.247C>T (p.Arg83Cys)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1062520	NM_001159699.2(FHL1):c.836G>A (p.Arg279His)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1312609	NM_001159699.2(FHL1):c.303C>G (p.Asn101Lys)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1379144	NM_001159699.2(FHL1):c.494A>G (p.Tyr165Cys)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1423972	NM_001159699.2(FHL1):c.77G>A (p.Cys26Tyr)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1430943	NM_001159699.2(FHL1):c.652G>A (p.Ala218Thr)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
198467	NM_001159699.2(FHL1):c.787G>A (p.Asp263Asn)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
285237	NM_001159699.2(FHL1):c.644G>A (p.Arg215His)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
286178	NM_001159699.2(FHL1):c.302A>G (p.Asn101Ser)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598055	NM_001159699.2(FHL1):c.704A>T (p.Lys235Met)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892146	NM_001159699.2(FHL1):c.464G>A (p.Gly155Glu)	FHL1	Uncertain significance	criteria provided, single submitter
3896867	NM_001159699.2(FHL1):c.483GGA[1] (p.Glu162del)	FHL1	Uncertain significance	criteria provided, single submitter
488949	NM_001159702.3(FHL1):c.-101+3A>G	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
568751	NM_001159699.2(FHL1):c.794G>C (p.Cys265Ser)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
647258	NM_001159699.2(FHL1):c.400A>G (p.Lys134Glu)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
665560	NM_001159699.2(FHL1):c.59A>G (p.Lys20Arg)	FHL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
816855	NM_001159699.2(FHL1):c.29C>G (p.Ser10Cys)	FHL1	Uncertain significance	no assertion criteria provided
198466	NM_001159699.2(FHL1):c.737-8C>T	FHL1	Benign	criteria provided, multiple submitters, no conflicts
469628	NM_001159699.2(FHL1):c.189C>T (p.Ile63=)	FHL1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FHL1	Definitive	X-linked	X-linked myopathy with postural muscle atrophy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FHL1	Orphanet:178461	X-linked myopathy with postural muscle atrophy
FHL1	Orphanet:431272	X-linked scapuloperoneal muscular dystrophy
FHL1	Orphanet:97239	Reducing body myopathy
FHL1	Orphanet:98863	X-linked Emery-Dreifuss muscular 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
FHL1	HGNC:3702	ENSG00000022267	Q13642	Four and a half LIM domains protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FHL1	Four and a half LIM domains protein 1	May have an involvement in muscle development or hypertrophy.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FHL1	Transcription factor	no		Znf_LIM, Fhl1, LIM_FHL1/2/3/5_N

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
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FHL1	291	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FHL1	1,431

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FHL1	Q13642	4

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
regulation of atrial cardiac muscle cell membrane depolarization	1	1872.4×	0.003	FHL1
negative regulation of G2/M transition of mitotic cell cycle	1	1123.5×	0.003	FHL1
positive regulation of potassium ion transmembrane transport	1	991.3×	0.003	FHL1
negative regulation of G1/S transition of mitotic cell cycle	1	358.6×	0.006	FHL1
animal organ morphogenesis	1	191.5×	0.008	FHL1
muscle organ development	1	166.8×	0.008	FHL1
negative regulation of cell growth	1	144.0×	0.008	FHL1
cell differentiation	1	29.1×	0.034	FHL1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FHL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FHL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FHL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.