OBSCN Gene (Obscurin, Cytoskeletal Calmodulin and Titin-Interacting RhoGEF)
Comprehensive genomic and proteomic analysis of OBSCN, a giant sarcomeric protein implicated in muscle development, cardiomyopathy, and cancer.
Gene Information Card
| Symbol | OBSCN |
|---|---|
| Full Name | Obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.13 |
| NCBI Gene ID | 84033 ncbi.nlm.nih.gov/gene/84033 |
| Ensembl ID | ENSG00000154358 |
| UniProt ID | Q5VST9 |
| OMIM ID | 608617 |
| HGNC ID | 28960 |
| Aliases | ARHGEF30, KIAA1639, UNC-89 homolog |
Description
OBSCN encodes obscurin, a giant sarcomeric protein (~720 kDa) that interacts with titin and calmodulin. It contains multiple immunoglobulin-like domains, a RhoGEF domain, and a serine/threonine kinase domain. Obscurin is essential for sarcomere assembly, myofibril alignment, and calcium signaling in striated muscle. Mutations in OBSCN are associated with dilated cardiomyopathy, hypertrophic cardiomyopathy, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy (DCM) | Loss-of-function mutations disrupt sarcomere integrity and calcium handling | ClinVar, PMID: 25525159 |
| Hypertrophic cardiomyopathy (HCM) | Missense variants alter obscurin-titin interaction leading to myocyte hypertrophy | ClinVar, PMID: 28416588 |
| Breast cancer | Somatic mutations (e.g., frameshift, nonsense) may impair cytoskeletal regulation | COSMIC, PMID: 22980975 |
| Colorectal cancer | Recurrent missense mutations in RhoGEF domain potentially alter signaling | COSMIC, PMID: 22681697 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 58.2 | High |
| Skeletal muscle | 42.1 | High |
| Brain | 1.3 | Low |
| Liver | 0.5 | Not detected |
| Kidney | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 62.4 | High expression; consistent with cardiac function |
| Skeletal muscle myotubes | 45.0 | High expression; myogenic differentiation |
| HEK293 | 0.2 | Very low; non-muscle background |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function; truncation of obscurin |
| c.4567G>A (p.Glu1523Lys) | Missense | 0.02% | Altered RhoGEF activity; associated with DCM |
| c.7890_7891insA (p.Leu2631Thrfs*5) | Frameshift | Somatic (COSMIC) | Loss of function; found in breast cancer |
| c.10234A>G (p.Thr3412Ala) | Missense | Somatic (COSMIC) | Unknown; recurrent in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein; associated with dilated cardiomyopathy and tumor suppression loss.
Gain of Function (GOF)
Not clearly established; some missense variants in RhoGEF domain may hyperactivate downstream signaling.
Dominant Negative (DN)
Potential for missense variants that disrupt obscurin-titin interaction and impair sarcomere assembly.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003779 – actin binding | • GO:0005085 – guanyl-nucleotide exchange factor activity |
| • GO:0005516 – calmodulin binding | • GO:0005856 – cytoskeleton |
| • GO:0030016 – myofibril | • GO:0031032 – actomyosin structure organization |
| • GO:0051015 – actin filament-based movement |
Pathways
• Sarcomere assembly and maintenance (Reactome: R-HSA-390522)
• Striated muscle contraction (Reactome: R-HSA-390522)
• Rho GTPase signaling (Reactome: R-HSA-194315)
Protein Summary
Obscurin is a giant modular protein (7968 amino acids) localized to the M-band and Z-disk of sarcomeres. It contains 67 Ig-like domains, 2 fibronectin type III domains, a RhoGEF domain, a pleckstrin homology domain, and a serine/threonine kinase domain. It interacts with titin, calmodulin, and small GTPases, regulating sarcomere organization and calcium homeostasis. Alternative splicing generates multiple isoforms with tissue-specific functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OBSCN Knockout HEK293 Cell Line | EDJ-KQ1966 | Human | 84033 | Details Get a Quote |
| OBSCN Knockout A-549 Cell Line | EDJ-KQ21932 | Human | 84033 | Details Get a Quote |
| OBSCN Knockout HCT 116 Cell Line | EDJ-KQ21933 | Human | 84033 | Details Get a Quote |
| OBSCN Knockout HeLa Cell Line | EDJ-KQ21934 | Human | 84033 | Details Get a Quote |
| OBSCN Knockout HAP1 Cell Line | EDC08249 | Human | 84033 | Details Get a Quote |
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