Rhabdomyolysis, susceptibility to, 1

Summary

Rhabdomyolysis, susceptibility to, 1 (MONDO:0859371) is a disease caused by OBSCN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: OBSCN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rhabdomyolysis, susceptibility to, 1
Mondo ID	MONDO:0859371
OMIM	620235
UMLS	C5774307
MedGen	1824080
Is cancer (heuristic)	no

Data availability: 33 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › rhabdomyolysis, susceptibility to › rhabdomyolysis, susceptibility to, 1

Related subtypes (1): rhabdomyolysis, susceptibility to, 2

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

33 retrieved; paginated sample, class counts are floors:

13 likely pathogenic, 7 uncertain significance, 4 risk factor, 3 benign, 2 conflicting classifications of pathogenicity, 2 pathogenic, 1 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3772679	NM_001386125.1(OBSCN):c.708del (p.Ala237fs)	OBSCN	Pathogenic	no assertion criteria provided
3774599	NM_001386125.1(OBSCN):c.2029C>A (p.Leu677Met)	OBSCN	Pathogenic	no assertion criteria provided
2060068	NM_001386125.1(OBSCN):c.7078+1G>T	OBSCN	Likely pathogenic	criteria provided, single submitter
2442245	NM_001386125.1(OBSCN):c.2653+1G>C	OBSCN	Likely pathogenic	criteria provided, single submitter
3237354	NM_001386125.1(OBSCN):c.8772_8793del (p.Pro2925fs)	OBSCN	Likely pathogenic	criteria provided, single submitter
3775261	NM_001386125.1(OBSCN):c.18922C>T (p.Arg6308Ter)	OBSCN	Likely pathogenic	criteria provided, single submitter
3780056	NM_001386125.1(OBSCN):c.13437_13438del (p.Cys4479fs)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813776	NM_001386125.1(OBSCN):c.5620C>T (p.Gln1874Ter)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813778	NM_001386125.1(OBSCN):c.8131C>T (p.Gln2711Ter)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813779	NM_001386125.1(OBSCN):c.12859C>T (p.Gln4287Ter)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813780	NM_001386125.1(OBSCN):c.15307C>T (p.Gln5103Ter)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813781	NM_001386125.1(OBSCN):c.19607C>A (p.Ser6536Ter)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813782	NM_001386125.1(OBSCN):c.23852del (p.Pro7951fs)	OBSCN	Likely pathogenic	criteria provided, single submitter
4813783	NM_001386125.1(OBSCN):c.24062del (p.Gly8021fs)	OBSCN	Likely pathogenic	criteria provided, single submitter
4846880	NM_001386125.1(OBSCN):c.23841dup (p.Gly7948fs)	OBSCN	Likely pathogenic	criteria provided, single submitter
2443848	NM_001386125.1(OBSCN):c.16230C>A (p.Cys5410Ter)	OBSCN	risk factor	no assertion criteria provided
2443849	NM_001386125.1(OBSCN):c.14818C>T (p.Arg4940Ter)	OBSCN	risk factor	no assertion criteria provided
2443850	NM_001386125.1(OBSCN):c.6102G>A (p.Trp2034Ter)	OBSCN	risk factor	no assertion criteria provided
2443852	NM_001386125.1(OBSCN):c.9563_9576del (p.Leu3188fs)	OBSCN	risk factor	no assertion criteria provided
1732223	NM_001386125.1(OBSCN):c.12740C>T (p.Thr4247Met)	OBSCN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2052988	NM_001386125.1(OBSCN):c.23385_23386del (p.Ala7795_Ser7796insTer)	OBSCN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2564863	NM_001386125.1(OBSCN):c.20573A>G (p.His6858Arg)	LOC112577546	Uncertain significance	criteria provided, multiple submitters, no conflicts
2501753	NM_001386125.1(OBSCN):c.4497_4498del (p.Val1500fs)	OBSCN	Uncertain significance	criteria provided, single submitter
3238830	NM_001386125.1(OBSCN):c.7975C>T (p.Pro2659Ser)	OBSCN	Uncertain significance	criteria provided, single submitter
3780055	NM_001386125.1(OBSCN):c.13428_13429del (p.Cys4479fs)	OBSCN	Uncertain significance	criteria provided, single submitter
3780057	NM_001386125.1(OBSCN):c.22305_22306del (p.Phe7436fs)	OBSCN	Uncertain significance	criteria provided, single submitter
4125013	NM_001386125.1(OBSCN):c.2396A>G (p.His799Arg)	OBSCN	Uncertain significance	criteria provided, multiple submitters, no conflicts
4846879	NM_001386125.1(OBSCN):c.1512C>T (p.Cys504=)	OBSCN	Uncertain significance	criteria provided, single submitter
3203858	NM_001386125.1(OBSCN):c.8552G>A (p.Gly2851Glu)	OBSCN	Likely benign	criteria provided, multiple submitters, no conflicts
618764	NM_001386125.1(OBSCN):c.20169C>T (p.Asp6723=)	OBSCN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
OBSCN	Strong	Autosomal recessive	rhabdomyolysis, susceptibility to, 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OBSCN	Orphanet:99845	Genetic recurrent myoglobinuria

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
OBSCN	HGNC:15719	ENSG00000154358	Q5VST9	Obscurin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OBSCN	Obscurin	Structural component of striated muscles which plays a role in myofibrillogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OBSCN	Kinase	yes		IQ_motif_EF-hand-BS, DH_dom, Prot_kinase_dom

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
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OBSCN	197	ubiquitous	marker	hindlimb stylopod muscle, apex of heart, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OBSCN	2,042

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OBSCN	Q5VST9	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
NRAGE signals death through JNK	1	184.2×	0.010	OBSCN
RHOQ GTPase cycle	1	181.3×	0.010	OBSCN
G alpha (12/13) signalling events	1	137.6×	0.010	OBSCN
RHOA GTPase cycle	1	74.6×	0.013	OBSCN

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
protein localization to M-band	1	8426.0×	4e-04	OBSCN
sarcomere organization	1	383.0×	0.004	OBSCN
regulation of small GTPase mediated signal transduction	1	144.0×	0.007	OBSCN

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
OBSCN	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	1	OBSCN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
OBSCN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.