OBSL1

obscurin like cytoskeletal adaptor 1, the group of I-set domain containing

Basic information

Region (hg38): 2:219550727-219571859

Links

ENSG00000124006 ∙ NCBI:23363 ∙ OMIM:610991 ∙ HGNC:29092 ∙ Uniprot:O75147 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3M syndrome 2 (Definitive), mode of inheritance: AR
• 3M syndrome 2 (Strong), mode of inheritance: AR
• 3-M syndrome (Supportive), mode of inheritance: AR
• 3M syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Three M syndrome 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Endocrine; Musculoskeletal	19481195; 23457316; 27796265

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OBSL1 gene.

• not provided (777 variants)
• 3M syndrome 2 (244 variants)
• Inborn genetic diseases (130 variants)
• not specified (58 variants)
• OBSL1-related condition (6 variants)
• 3-M syndrome (5 variants)
• 12 conditions (2 variants)
• Short stature (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OBSL1 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			26	145	32	203
missense			454	16	17	487
nonsense	6	4	10			20
start loss						0
frameshift	11	14	12			37
inframe indel			3			3
splice donor/acceptor (+/-2bp)		4	2	1		7
splice region			10	12	4	26
non coding			16	29	47	92
Total	17	22	523	191	96

Highest pathogenic variant AF is 0.000118

Variants in OBSL1

This is a list of pathogenic ClinVar variants found in the OBSL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-219550732-C-CTA		3-M syndrome	Uncertain significance (Jun 14, 2016)
2-219550846-C-T			Likely benign (Jul 12, 2022)
2-219550873-GGA-G		3M syndrome 2	Benign (Sep 05, 2021)
2-219550924-T-C			Benign (Nov 12, 2018)
2-219550995-G-A			Benign (Nov 12, 2018)
2-219551030-C-T			Benign (Jun 19, 2021)
2-219551112-A-G			Benign (Nov 12, 2018)
2-219551442-T-C			Benign (Nov 12, 2018)
2-219551528-C-G		not specified	Uncertain significance (Jan 06, 2023)
2-219551536-C-T		3M syndrome 2	Benign/Likely benign (Jan 22, 2024)
2-219551555-C-T		3M syndrome 2	Uncertain significance (Jan 13, 2018)
2-219551556-T-C			Uncertain significance (Jul 01, 2023)
2-219551559-C-T			Uncertain significance (Jul 17, 2022)
2-219551566-G-C			Likely benign (Jan 13, 2023)
2-219551568-C-T			Uncertain significance (Aug 28, 2021)
2-219551571-G-C			Uncertain significance (May 23, 2023)
2-219551600-C-T			Uncertain significance (Aug 17, 2023)
2-219551619-G-A		3M syndrome 2	Conflicting classifications of pathogenicity (Dec 09, 2023)
2-219551621-C-CT		not specified	Uncertain significance (Jan 23, 2024)
2-219551623-G-A			Likely benign (Sep 10, 2023)
2-219551624-T-C		Inborn genetic diseases	Uncertain significance (Feb 13, 2023)
2-219551639-C-G			Uncertain significance (Jul 17, 2021)
2-219551648-T-C		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
2-219551654-T-C		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
2-219551655-T-TGA		3M syndrome 2	Likely pathogenic (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OBSL1	protein_coding	protein_coding	ENST00000404537	21	21131

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.99e-26	0.722	123979	2	1160	125141	0.00465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00685	1170	1.17e+3	0.999	0.0000776	11872
Missense in Polyphen		427	426.77	1.0005		4414
Synonymous	-0.193	517	511	1.01	0.0000347	4136
Loss of Function	2.42	51	73.4	0.695	0.00000410	750

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0166	0.0159
Ashkenazi Jewish	0.0154	0.0153
East Asian	0.00284	0.00278
Finnish	0.00423	0.00423
European (Non-Finnish)	0.00368	0.00363
Middle Eastern	0.00284	0.00278
South Asian	0.00161	0.00157
Other	0.00666	0.00657

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696). Acts as a regulator of the Cul7-RING(FBXW8) ubiquitin-protein ligase, playing a critical role in the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Required to localize CUL7 to the Golgi apparatus in neurons. {ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Neddylation (Consensus)

Intolerance Scores

• loftool: 0.861
• rvis_EVS: -0.81
• rvis_percentile_EVS: 12.02

Haploinsufficiency Scores

• pHI: 0.183
• hipred: N
• hipred_score: 0.478
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Obsl1

Gene ontology

• Biological process: microtubule cytoskeleton organization;muscle contraction;cytoskeleton organization;Golgi organization;regulation of mitotic nuclear division;skeletal muscle thin filament assembly;skeletal muscle myosin thick filament assembly;protein localization to Golgi apparatus;post-translational protein modification;sarcomere organization;cardiac muscle fiber development;positive regulation of dendrite morphogenesis;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;striated muscle myosin thick filament assembly
• Cellular component: cytoplasm;Golgi apparatus;centrosome;cytosol;striated muscle thin filament;intercalated disc;sarcomere;Z disc;M band;perinuclear region of cytoplasm;3M complex
• Molecular function: protein binding;cytoskeletal adaptor activity;structural constituent of muscle;actin filament binding;muscle alpha-actinin binding