Spinal muscular atrophy, facioscapulohumeral type

Summary

Spinal muscular atrophy, facioscapulohumeral type (MONDO:0008452) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinal muscular atrophy, facioscapulohumeral type
Mondo ID	MONDO:0008452
MeSH	C566674
OMIM	182970
UMLS	C1866783
MedGen	357136
GARD	0024622
Is cancer (heuristic)	no

Also known as: spinal muscular atrophy, facioscapulohumeral type

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › spinal muscular atrophy › spinal muscular atrophy, facioscapulohumeral type

Related subtypes (18): spinal muscular atrophy-progressive myoclonic epilepsy syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, adult-onset proximal spinal muscular atrophy, autosomal dominant, spinal muscular atrophy, segmental, spinal muscular atrophy, Ryukyuan type, scapuloperoneal spinal muscular atrophy, autosomal recessive, X-linked distal spinal muscular atrophy type 3, infantile-onset X-linked spinal muscular atrophy, autosomal recessive distal spinal muscular atrophy 1, autosomal recessive distal spinal muscular atrophy 2, neuronopathy, distal hereditary motor, autosomal recessive 3, neuronopathy, distal hereditary motor, autosomal recessive 4, neuronopathy, distal hereditary motor, autosomal recessive 5, neuronopathy, distal hereditary motor, autosomal dominant, bulbospinal muscular atrophy, spinal muscular atrophy with respiratory distress type 2, proximal spinal muscular atrophy, spinal muscular atrophy type 0

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
549691	NM_020631.6(PLEKHG5):c.58del (p.Arg20fs)	PLEKHG5	Pathogenic	criteria provided, single submitter

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
PLEKHG5	Orphanet:206580	Autosomal recessive lower motor neuron disease with childhood onset
PLEKHG5	Orphanet:369867	Autosomal recessive intermediate Charcot-Marie-Tooth disease type C

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
PLEKHG5	HGNC:29105	ENSG00000171680	O94827	Pleckstrin homology domain-containing family G member 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLEKHG5	Pleckstrin homology domain-containing family G member 5	Functions as a guanine exchange factor (GEF) for RAB26 and thus regulates autophagy of synaptic vesicles in axon terminal of motoneurons.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLEKHG5	Scaffold/PPI	no		DH_dom, PH_domain, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
cerebellar hemisphere	1
right hemisphere of cerebellum	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLEKHG5	175	ubiquitous	yes	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLEKHG5	966

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLEKHG5	O94827	64.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RND1 GTPase cycle	1	265.6×	0.009	PLEKHG5
RND3 GTPase cycle	1	259.6×	0.009	PLEKHG5
NRAGE signals death through JNK	1	184.2×	0.009	PLEKHG5
G alpha (12/13) signalling events	1	137.6×	0.009	PLEKHG5
RHOA GTPase cycle	1	74.6×	0.013	PLEKHG5

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
endothelial cell chemotaxis	1	1685.2×	0.003	PLEKHG5
endothelial cell migration	1	411.0×	0.006	PLEKHG5
Rho protein signal transduction	1	247.8×	0.007	PLEKHG5
regulation of small GTPase mediated signal transduction	1	144.0×	0.009	PLEKHG5
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.014	PLEKHG5

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
PLEKHG5	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	PLEKHG5

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)
PLEKHG5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.