Rhabdomyolysis, susceptibility to, 2

Summary

Rhabdomyolysis, susceptibility to, 2 (MONDO:0980721) 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	rhabdomyolysis, susceptibility to, 2
Mondo ID	MONDO:0980721
OMIM	621236
UMLS	C6012738
MedGen	1876478
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › rhabdomyolysis, susceptibility to › rhabdomyolysis, susceptibility to, 2

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

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 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
3901866	ATP2A2, ARG528GLN	ATP2A2	risk factor	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
ATP2A2	Orphanet:218	Darier disease
ATP2A2	Orphanet:79151	Acrokeratosis verruciformis of Hopf

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
ATP2A2	HGNC:812	ENSG00000174437	P16615	Sarcoplasmic/endoplasmic reticulum calcium ATPase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP2A2	Sarcoplasmic/endoplasmic reticulum calcium ATPase 2	This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen.

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)
ATP2A2	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIA

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
heart right ventricle	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP2A2	304	ubiquitous	marker	heart right ventricle, skeletal muscle tissue of biceps brachii, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP2A2	807

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP2A2	P16615	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Reduction of cytosolic Ca++ levels	1	951.7×	0.007	ATP2A2
Platelet calcium homeostasis	1	713.8×	0.007	ATP2A2
Pre-NOTCH Processing in Golgi	1	634.4×	0.007	ATP2A2
Pre-NOTCH Expression and Processing	1	368.4×	0.010	ATP2A2
Platelet homeostasis	1	278.5×	0.010	ATP2A2
Ion transport by P-type ATPases	1	207.6×	0.010	ATP2A2
Ion homeostasis	1	203.9×	0.010	ATP2A2
Signaling by NOTCH	1	175.7×	0.010	ATP2A2
Cardiac conduction	1	108.8×	0.014	ATP2A2
Ion channel transport	1	96.0×	0.015	ATP2A2
Muscle contraction	1	77.2×	0.016	ATP2A2
Hemostasis	1	36.0×	0.032	ATP2A2
Transport of small molecules	1	25.1×	0.043	ATP2A2
Signal Transduction	1	10.2×	0.098	ATP2A2

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
ER-nucleus signaling pathway	1	16852.0×	9e-04	ATP2A2
regulation of calcium ion-dependent exocytosis of neurotransmitter	1	8426.0×	9e-04	ATP2A2
calcium ion transport from cytosol to endoplasmic reticulum	1	8426.0×	9e-04	ATP2A2
positive regulation of endoplasmic reticulum calcium ion concentration	1	5617.3×	9e-04	ATP2A2
organelle localization by membrane tethering	1	5617.3×	9e-04	ATP2A2
calcium ion import into sarcoplasmic reticulum	1	5617.3×	9e-04	ATP2A2
negative regulation of heart contraction	1	4213.0×	0.001	ATP2A2
sarcoplasmic reticulum calcium ion transport	1	3370.4×	0.001	ATP2A2
T-tubule organization	1	2808.7×	0.001	ATP2A2
transition between fast and slow fiber	1	2407.4×	0.001	ATP2A2
autophagosome membrane docking	1	2407.4×	0.001	ATP2A2
regulation of cardiac muscle cell membrane potential	1	2407.4×	0.001	ATP2A2
obsolete mitochondrion-endoplasmic reticulum membrane tethering	1	2106.5×	0.001	ATP2A2
regulation of cardiac muscle cell action potential involved in regulation of contraction	1	1872.4×	0.001	ATP2A2
regulation of cardiac muscle contraction by calcium ion signaling	1	1296.3×	0.001	ATP2A2
relaxation of cardiac muscle	1	1296.3×	0.001	ATP2A2
positive regulation of cardiac muscle cell apoptotic process	1	1203.7×	0.002	ATP2A2
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.002	ATP2A2
regulation of the force of heart contraction	1	991.3×	0.002	ATP2A2
endoplasmic reticulum calcium ion homeostasis	1	842.6×	0.002	ATP2A2
regulation of cardiac conduction	1	842.6×	0.002	ATP2A2
positive regulation of heart rate	1	702.2×	0.002	ATP2A2
neuron cellular homeostasis	1	455.5×	0.003	ATP2A2
autophagosome assembly	1	224.7×	0.006	ATP2A2
epidermis development	1	210.7×	0.006	ATP2A2
calcium ion transmembrane transport	1	210.7×	0.006	ATP2A2
monoatomic ion transmembrane transport	1	208.1×	0.006	ATP2A2
response to endoplasmic reticulum stress	1	166.8×	0.007	ATP2A2
cellular response to oxidative stress	1	154.6×	0.007	ATP2A2
intracellular calcium ion homeostasis	1	145.3×	0.007	ATP2A2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · 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
ATP2A2	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CURCUMIN	3	ATP2A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP2A2	19	Binding:19

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)
CURCUMIN	3	ATP2A2

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	ATP2A2
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.