GeneBe

OBSCN

obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF, the group of Fibronectin type III domain containing|I-set domain containing|Dbl family Rho GEFs|Myosin light chain kinase family

Basic information

Region (hg38): 1:228208044-228378876

Links

ENSG00000154358 ∙ NCBI:84033 ∙ OMIM:608616 ∙ HGNC:15719 ∙ Uniprot:Q5VST9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • rhabdomyolysis, susceptibility to, 1 (Strong), mode of inheritance: AR
  • hypertrophic cardiomyopathy (Limited), mode of inheritance: AD
  • dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Rhabdomyolysis, susceptibility to, 1ARMusculoskeletal; RenalThe condition can include increased risk of rhabdomyolysis, due both to risk factors such as exercise and heat, as well as spontaneously, with risk of renal damage and compartment syndrome, and awareness may allow preventative measures and prompt treatment of episodesMusculoskeletal; Renal34957489

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OBSCN gene.

  • not_specified (4961 variants)
  • not_provided (577 variants)
  • OBSCN-related_disorder (294 variants)
  • Rhabdomyolysis,_susceptibility_to,_1 (23 variants)
  • Short_stature (3 variants)
  • Inborn_genetic_diseases (2 variants)
  • Arrhythmogenic_right_ventricular_dysplasia_9 (1 variants)
  • Hearing_loss,_autosomal_recessive_120 (1 variants)
  • Hypertrophic_cardiomyopathy_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OBSCN gene is commonly pathogenic or not. These statistics are base on transcript: NM_001386125.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
1482
clinvar
43
clinvar
 1527
missense
1
clinvar
2
clinvar
2689
clinvar
645
clinvar
71
clinvar
 3408
nonsense
12
clinvar
1
clinvar
9
clinvar
1
clinvar
 23
start loss
0
frameshift
18
clinvar
5
clinvar
7
clinvar
3
clinvar
 33
splice donor/acceptor (+/-2bp)
2
clinvar
7
clinvar
1
clinvar
1
clinvar
 11
Total 33 15 2707 2132 115

Highest pathogenic variant AF is 0.00032663564

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
OBSCNprotein_codingprotein_codingENST00000570156 115170747
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.86e-1642.46e-1211602088681541250600.0368
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.1455365.30e+31.040.00036356590
Missense in Polyphen25142487.21.010828018
Synonymous-1.9924902.37e+31.050.00017518677
Loss of Function3.712973750.7930.00001904191

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.03390.0327
Ashkenazi Jewish0.009660.00958
East Asian0.3170.311
Finnish0.04030.0396
European (Non-Finnish)0.008730.00828
Middle Eastern0.3170.311
South Asian0.05240.0512
Other0.02900.0279

dbNSFP

Source: dbNSFP

Function
FUNCTION: Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939}.;
Disease
DISEASE: Note=A chromosomal aberration involving OBSCN has been found in Wilms tumor. Translocation t(1;7)(q42;p15) with PTHB1. {ECO:0000269|PubMed:12618763}.;
Pathway
Signaling by GPCR;Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;Cell death signalling via NRAGE, NRIF and NADE;Regulation of RhoA activity (Consensus)

Recessive Scores

pRec
0.128

Haploinsufficiency Scores

pHI
0.180
hipred
N
hipred_score
0.270
ghis
0.514

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.528

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Obscn
Phenotype
muscle phenotype;

Zebrafish Information Network

Gene name
obscnb
Affected structure
cardiac muscle cell
Phenotype tag
abnormal
Phenotype quality
structure

Gene ontology

Biological process
protein phosphorylation;G protein-coupled receptor signaling pathway;multicellular organism development;regulation of Rho protein signal transduction;protein localization to M-band;positive regulation of apoptotic process;sarcomere organization;regulation of small GTPase mediated signal transduction
Cellular component
cytosol;plasma membrane;nuclear body;myofibril;Z disc;M band;sarcolemma
Molecular function
protein serine/threonine kinase activity;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding;calmodulin binding;ATP binding;structural constituent of muscle;ankyrin binding;titin binding;metal ion binding