OSBPL2

oxysterol binding protein like 2, the group of Oxysterol binding proteins

Basic information

Region (hg38): 20:62231922-62296213

Links

ENSG00000130703 ∙ NCBI:9885 ∙ OMIM:606731 ∙ HGNC:15761 ∙ Uniprot:Q9H1P3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 67 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 67 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 67 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 67	AD	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	Audiologic/Otolaryngologic	25077649; 25759012

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OSBPL2 gene.

• Autosomal dominant nonsyndromic hearing loss 67 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OSBPL2 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				34	3	37
missense			54	2	2	58
nonsense			1			1
start loss						0
frameshift	1		1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			4	7	4	15
non coding			2	50	41	93
Total	1	0	58	86	46

Variants in OSBPL2

This is a list of pathogenic ClinVar variants found in the OSBPL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-62238609-C-T		not specified	Benign (Feb 11, 2020)
20-62256056-G-C			Uncertain significance (Nov 14, 2023)
20-62256189-A-G			Uncertain significance (Mar 04, 2022)
20-62256214-C-T		not specified	Likely benign (Dec 21, 2017)
20-62256228-CAAAAG-C		OSBPL2-related disorder	Likely benign (Aug 20, 2019)
20-62256244-G-A		Autosomal dominant nonsyndromic hearing loss 67	Benign (Sep 05, 2021)
20-62256323-C-G			Likely benign (Jun 23, 2019)
20-62256373-C-A			Benign (Nov 29, 2018)
20-62259751-GGCACTGGAGCTCGCTGGGA-G			Benign (Dec 17, 2018)
20-62259975-G-A			Benign (Dec 25, 2023)
20-62259988-T-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
20-62260001-T-C			Uncertain significance (Mar 02, 2023)
20-62260009-A-G			Likely benign (Jan 04, 2024)
20-62260019-G-A		not specified	Benign (Jan 18, 2024)
20-62260032-T-A		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
20-62260043-A-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
20-62260044-T-C		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
20-62260067-A-C			Uncertain significance (Mar 19, 2022)
20-62260071-G-T			Uncertain significance (Mar 10, 2022)
20-62260083-CTG-C		Autosomal dominant nonsyndromic hearing loss 67	Pathogenic (Feb 10, 2015)
20-62260094-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
20-62260095-CCT-C		Autosomal dominant nonsyndromic hearing loss 67	Pathogenic (Mar 01, 2015)
20-62260100-CAA-C		Autosomal dominant nonsyndromic hearing loss 67	Pathogenic (Jun 20, 2022)
20-62260101-A-G			Uncertain significance (Jul 25, 2022)
20-62260105-G-C			Uncertain significance (Sep 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OSBPL2	protein_coding	protein_coding	ENST00000313733	13	57689

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.131	0.869	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.97	197	292	0.675	0.0000171	3194
Missense in Polyphen		56	142.43	0.39318		1473
Synonymous	0.608	112	120	0.930	0.00000857	858
Loss of Function	3.61	7	27.4	0.256	0.00000125	320

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000619	0.0000619
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000704	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3- phosphate (PubMed:11279184). Binds 25-hydroxycholesterol (PubMed:17428193). {ECO:0000269|PubMed:11279184, ECO:0000269|PubMed:17428193}.
• Pathway: Metabolism of lipids;Metabolism;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.608
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.121
• hipred: Y
• hipred_score: 0.661
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Osbpl2

Gene ontology

• Biological process: bile acid biosynthetic process;sterol transport
• Cellular component: cytosol;membrane;intracellular membrane-bounded organelle
• Molecular function: protein binding;lipid binding;sterol transporter activity;cholesterol binding;sterol binding