OSBPL1A

protein-coding

oxysterol binding protein like 1A, the group of Ankyrin repeat domain containing|Oxysterol binding proteins

Gene summary

This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms. [provided by RefSeq, Jul 2008]

Previous symbols:

OSBPL1B

MANE transcript

NM_080597.4

Inheritance

—

ClinVar variants

P:1U:115B:3

Top phenotype

Familial hypercholesterolemia

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr18:24,162,045-24,397,880

External References & Databases

Ensembl (ENSG00000141447)

Transcript & Mutation Effects

hg38 • Region Span ~235.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OSBPL1A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 103

Familial hypercholesterolemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080597.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	1 clinvar		5
missense			107 clinvar	2 clinvar		109
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	115	3	0	119

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080597.4	RefSeq	NP_542164.2	27	MANE Select
ENST00000319481.8	Ensembl	ENSP00000320291.3	27	MANE Select
NM_001242508.1	RefSeq	NP_001229437.1	15	Standard
NM_018030.4	RefSeq	NP_060500.3	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Synthesis of bile acids and bile salts
Bile acid and bile salt metabolism
Metabolism of steroids

Biological Process

bile acid biosynthetic process
cholesterol metabolic process
sterol transport
vesicle-mediated transport
antigen processing and presentation of exogenous peptide antigen via MHC class II

Molecular Function

protein binding
phospholipid binding
lipid binding
sterol transporter activity
cholesterol binding

Cellular Component

late endosome
cytosol
membrane
intracellular membrane-bounded organelle
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319481
Coding exons: 27
Length: 235837
Individuals with no LoFs: 125076
Homozygous LoFs: 1
Heterozygous LoFs: 671
Defined: 125748
p: 0.00268

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	405	503	0.805	0.0000256	6304
Missense (PolyPhen)		109	177.33	0.61467		2141
Synonymous	0.00543	182	182	0.999	0.00000988	1685
Loss of Function	4.62	23	62.4	0.369	0.00000326	731

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0019	0.0018	notable
Latino/Admixed American	0.0042	0.0039	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.0037	0.0036	notable
South Asian	0.0019	0.0018	notable
Other	0.0042	0.0039	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3- phosphate (By similarity). Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A (PubMed:16176980). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000250, ECO:0000269|PubMed:16176980, ECO:0000269|PubMed:17428193}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.877
RVIS EVS: -0.42
RVIS percentile EVS: 25.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.638

Gene Damage Prediction

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