OSBP

protein-coding

oxysterol binding protein, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes|Oxysterol binding proteins

Gene summary

Oxysterol binding protein is an intracellular protein that is believed to transport sterols from lysosomes to the nucleus where the sterol down-regulates the genes for the LDL receptor, HMG-CoA reductase, and HMG synthetase [provided by RefSeq, Jul 2008]

MANE transcript

NM_002556.3

Inheritance

—

ClinVar variants

P:1U:75B:8

Top phenotype

OSBP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr11:59,574,398-59,615,774

External References & Databases

Ensembl (ENSG00000110048)

Transcript & Mutation Effects

hg38 • Region Span ~41.4 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 OSBP variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 68

OSBP-related disorderTotal: 7

not providedTotal: 4

Short statureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002556.3. 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			1 clinvar	4 clinvar	2 clinvar	7
missense			71 clinvar	2 clinvar		73
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	75	6	2	84

Highest pathogenic variant AF is 6.840872e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002556.3	RefSeq	NP_002547.1	14	MANE Select
ENST00000263847.6	Ensembl	ENSP00000263847.1	14	MANE Select
ENST00000525357.1	Ensembl	ENSP00000432399.1	4	Standard
ENST00000937173.1	Ensembl	ENSP00000607232.1	14	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
sterol transport
intracellular cholesterol transport
positive regulation of growth of symbiont in host

Molecular Function

protein binding
oxysterol binding
lipid binding
sterol transporter activity
protein domain specific binding

Cellular Component

Golgi membrane
nucleus
nucleoplasm
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263847
Coding exons: 14
Length: 41747
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.58	214	421	0.508	0.0000234	5259
Missense (PolyPhen)		66	197	0.33502		2305
Synonymous	-0.125	157	155	1.01	0.00000832	1573
Loss of Function	5.42	6	45.5	0.132	0.00000290	473

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum (PubMed:24209621). Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol (PubMed:15746430, PubMed:17428193). Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly (PubMed:15746430). Regulates cholesterol efflux by decreasing ABCA1 stability (PubMed:18450749). {ECO:0000269|PubMed:15746430, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18450749, ECO:0000269|PubMed:24209621}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.256
RVIS EVS: -0.8
RVIS percentile EVS: 12.24

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

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