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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
OBSCN
obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF
Chromosome 1 Β· 1q42.13
NCBI Gene: 84033Ensembl: ENSG00000154358.23HGNC: HGNC:15719UniProt: A0ABB0H0G2
90PubMed Papers
20Diseases
0Drugs
56Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
titin bindingphosphatidylinositol-3-phosphate bindingphosphatidylinositol-3,4-bisphosphate bindingcytosolAbnormality of the skeletal systemAcute rhabdomyolysisgenetic disorderhereditary recurrent myoglobinuria
✦AI Summary

OBSCN encodes obscurin, a giant cytoskeletal protein essential for muscle fiber structural integrity and function in both cardiac and skeletal muscle 1. The protein serves as a structural constituent of muscle and plays key roles in sarcomere organization, localizing to the M-band, Z disc, and sarcolemma 2. OBSCN functions as a guanyl-nucleotide exchange factor with RhoGEF activity and exhibits protein kinase activity, regulating small GTPase-mediated signal transduction. The gene undergoes extensive alternative splicing during human cardiac and skeletal muscle development, producing tissue-specific isoforms 3. Truncating variants in OBSCN are significantly associated with hypertrophic cardiomyopathy (HCM), with affected patients showing increased risk of cardiovascular death and all-cause mortality 4. OBSCN mutations have been linked to various cardiomyopathies including HCM, dilated cardiomyopathy, and left ventricular non-compaction 25. The protein shows age-related mutation patterns, being a top mutated gene in adult cardiomyopathy patients and enriched for protein-truncating variants 6. Additionally, OBSCN variants have been associated with rhabdomyolysis, demonstrating the protein's critical role in maintaining muscle fiber integrity 1.

Sources cited
1
OBSCN encodes obscurin, essential for muscle fiber structural integrity and associated with rhabdomyolysis
PMID: 40813169
2
Obscurin serves as structural constituent and plays regulatory roles in striated muscles
PMID: 30099631
3
OBSCN undergoes extensive alternative splicing during cardiac and skeletal muscle development
PMID: 40025502
4
OBSCN truncating variants are associated with HCM and increased mortality risk
PMID: 34601892
5
OBSCN mutations linked to HCM, DCM, and LVNC cardiomyopathies
PMID: 28510120
6
OBSCN is a top mutated gene in adult cardiomyopathy patients with protein-truncating variants
PMID: 37477868
Disease Associationsβ“˜20
Abnormality of the skeletal systemOpen Targets
0.63Moderate
Acute rhabdomyolysisOpen Targets
0.41Moderate
genetic disorderOpen Targets
0.37Weak
hereditary recurrent myoglobinuriaOpen Targets
0.37Weak
atrial fibrillationOpen Targets
0.37Weak
Short statureOpen Targets
0.34Weak
hearing loss, autosomal recessive 120Open Targets
0.33Weak
hypertensionOpen Targets
0.30Weak
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.29Weak
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.29Weak
hypertrophic cardiomyopathy 1Open Targets
0.28Weak
essential hypertensionOpen Targets
0.27Weak
musculoskeletal system diseaseOpen Targets
0.26Weak
cardiomyopathyOpen Targets
0.13Weak
atrial flutterOpen Targets
0.12Weak
dilated cardiomyopathyOpen Targets
0.10Weak
hypertrophic cardiomyopathyOpen Targets
0.09Suggestive
Romano-Ward syndromeOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
premature birthOpen Targets
0.08Suggestive
Pathogenic Variants56
NM_001386125.1(OBSCN):c.19663C>T (p.Arg6555Ter)Pathogenic
Acute rhabdomyolysis
β˜…β˜†β˜†β˜†2025β†’ Residue 6555
NM_001386125.1(OBSCN):c.10024+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001386125.1(OBSCN):c.24476_24492del (p.Gly8159fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 8159
NM_001386125.1(OBSCN):c.23852del (p.Pro7951fs)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 7951
NM_001386125.1(OBSCN):c.24062del (p.Gly8021fs)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 8021
NM_001386125.1(OBSCN):c.19607C>A (p.Ser6536Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 6536
NM_001386125.1(OBSCN):c.12859C>T (p.Gln4287Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 4287
NM_001386125.1(OBSCN):c.8131C>T (p.Gln2711Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 2711
NM_001386125.1(OBSCN):c.5620C>T (p.Gln1874Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 1874
NM_001386125.1(OBSCN):c.15307C>T (p.Gln5103Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2025β†’ Residue 5103
NM_001386125.1(OBSCN):c.21797_21798delinsG (p.Thr7266fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 7266
NM_001386125.1(OBSCN):c.23500C>T (p.Gln7834Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2024β†’ Residue 7834
NM_001386125.1(OBSCN):c.19611dup (p.Pro6538fs)Likely pathogenic
Arrhythmogenic right ventricular dysplasia 9;Hypertrophic cardiomyopathy 1
β˜…β˜†β˜†β˜†2024β†’ Residue 6538
NM_001386125.1(OBSCN):c.9558_9559insT (p.Val3187fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 3187
NM_001386125.1(OBSCN):c.17566dup (p.Met5856fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 5856
NM_001386125.1(OBSCN):c.8772_8793del (p.Pro2925fs)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2024β†’ Residue 2925
NM_001386125.1(OBSCN):c.9434_9438del (p.Tyr3145fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 3145
NM_001386125.1(OBSCN):c.18922C>T (p.Arg6308Ter)Likely pathogenic
Rhabdomyolysis, susceptibility to, 1
β˜…β˜†β˜†β˜†2023β†’ Residue 6308
NM_001386125.1(OBSCN):c.21187+1G>TLikely pathogenic
OBSCN-related disorder
β˜…β˜†β˜†β˜†2023
NM_001386125.1(OBSCN):c.6313del (p.Val2105fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 2105
View on ClinVar β†—
Related Genes
ANK1Protein interaction99%ANK2Protein interaction99%TTNProtein interaction99%TCAPProtein interaction99%ANK3Protein interaction91%CALM3Protein interaction89%
Tissue Expression6 tissues
Heart
100%
Lung
17%
Ovary
14%
Bone Marrow
2%
Liver
2%
Brain
2%
Gene Interaction Network
Click a node to explore
OBSCNANK1ANK2TTNTCAPANK3CALM3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt A6NGQ3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.01LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.95 [0.89–1.01]
RankingsWhere OBSCN stands among ~20K protein-coding genes
  • #5,323of 20,598
    Most Researched90
  • #1,230of 5,498
    Most Pathogenic Variants56 Β· top quartile
  • #9,772of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedOBSCN
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Age and Sex Differences in the Genetics of Cardiomyopathy.
PMID: 37477868
J Cardiovasc Transl Res Β· 2023
1.00
2
Reevaluation of genetic variants previously associated with arrhythmogenic right ventricular cardiomyopathy integrating population-based cohorts and proteomics data.
PMID: 31402444
Clin Genet Β· 2019
0.90
3
OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development.
PMID: 40025502
Skelet Muscle Β· 2025
0.80
4
Truncating Variants in
PMID: 34601892
Circ Genom Precis Med Β· 2021
0.70
5
Rhabdomyolysis associated with OBSCN mutations: case report and mechanistic review.
PMID: 40813169
Neuromuscul Disord Β· 2025
0.60