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): 1:228208043-228378876

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rhabdomyolysis, susceptibility to, 1	AR	Musculoskeletal; Renal	The 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 episodes	Musculoskeletal; Renal	34957489

ClinVar

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

• Inborn genetic diseases (2960 variants)
• not provided (469 variants)
• not specified (15 variants)
• OBSCN-related condition (4 variants)
• Rhabdomyolysis, susceptibility to, 1 (3 variants)
• Short stature (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1088	36	1124
missense			1335	443	56	1834
nonsense	11		4	1		16
start loss						0
frameshift	13		1		1	15
inframe indel						0
splice donor/acceptor (+/-2bp)	1	7		1	1	10
splice region				15	1	16
non coding			75	107	7	189
Total	25	7	1415	1640	101

Highest pathogenic variant AF is 0.0000949

Variants in OBSCN

This is a list of pathogenic ClinVar variants found in the OBSCN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-228211781-C-G			Benign (Dec 12, 2018)
1-228211804-C-A		not specified	Uncertain significance (Oct 02, 2023)
1-228211817-T-G		not specified	Uncertain significance (Dec 06, 2022)
1-228211818-T-A		OBSCN-related disorder	Conflicting classifications of pathogenicity (Dec 01, 2022)
1-228211824-C-A		not specified	Uncertain significance (Nov 08, 2023)
1-228211826-C-G		not specified	Uncertain significance (Jul 14, 2022)
1-228211826-C-T		not specified	Uncertain significance (Sep 12, 2022)
1-228211849-G-C		not specified	Likely benign (Nov 27, 2022)
1-228211850-G-A		not specified	Likely benign (Apr 07, 2022)
1-228211867-C-G		not specified	Likely benign (May 22, 2023)
1-228211870-C-T		not specified	Likely benign (Jan 03, 2024)
1-228211886-G-C		not specified	Uncertain significance (Aug 11, 2022)
1-228211892-C-G		not specified	Uncertain significance (Jun 28, 2023)
1-228211897-G-A		not specified	Likely benign (Jan 22, 2023)
1-228211913-G-A		not specified	Uncertain significance (Apr 18, 2023)
1-228211918-G-C		not specified	Likely benign (Nov 10, 2022)
1-228211927-G-A		OBSCN-related disorder • not specified	Benign/Likely benign (Feb 11, 2022)
1-228211930-G-T		not specified	Likely benign (Jun 10, 2021)
1-228211935-C-T		not specified	Uncertain significance (Nov 17, 2023)
1-228211936-G-A		not specified	Likely benign (Nov 27, 2020)
1-228211940-G-T		not specified	Uncertain significance (Oct 05, 2023)
1-228211942-C-T		not specified	Likely benign (Dec 10, 2023)
1-228211953-G-T		not specified	Uncertain significance (Dec 22, 2023)
1-228211968-G-A		not specified	Uncertain significance (Aug 17, 2022)
1-228211970-G-A		OBSCN-related disorder	Benign (Apr 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OBSCN	protein_coding	protein_coding	ENST00000570156	115	170747

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.86e-164	2.46e-12	116020	886	8154	125060	0.0368

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.14	5536	5.30e+3	1.04	0.000363	56590
Missense in Polyphen		2514	2487.2	1.0108		28018
Synonymous	-1.99	2490	2.37e+3	1.05	0.000175	18677
Loss of Function	3.71	297	375	0.793	0.0000190	4191

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0339	0.0327
Ashkenazi Jewish	0.00966	0.00958
East Asian	0.317	0.311
Finnish	0.0403	0.0396
European (Non-Finnish)	0.00873	0.00828
Middle Eastern	0.317	0.311
South Asian	0.0524	0.0512
Other	0.0290	0.0279

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
• gene_indispensability_pred: E
• gene_indispensability_score: 0.528

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

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