OSBPL5

protein-coding

oxysterol binding protein like 5, the group of Pleckstrin homology 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 that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

MANE transcript

NM_020896.4

Inheritance

—

ClinVar variants

U:162B:19

Top phenotype

OSBPL5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr11:3,087,107-3,166,739

External References & Databases

Ensembl (ENSG00000021762)

Transcript & Mutation Effects

hg38 • Region Span ~79.6 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 OSBPL5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 167

not providedTotal: 11

OSBPL5-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020896.4. 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			1 clinvar	3 clinvar	2 clinvar	6
missense			158 clinvar	11 clinvar	3 clinvar	172
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	162	14	5	181

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020896.4	RefSeq	NP_065947.1	21	MANE Select
ENST00000263650.12	Ensembl	ENSP00000263650.7	21	MANE Select
NM_001144063.2	RefSeq	NP_001137535.1	20	Standard
NM_145638.3	RefSeq	NP_663613.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cholesterol metabolism - Homo sapiens (human)
Metabolism of lipids
Metabolism
Acyl chain remodelling of PS
Glycerophospholipid biosynthesis

Biological Process

Golgi to plasma membrane transport
cholesterol metabolic process
phospholipid transport
cholesterol transport
phosphatidylserine acyl-chain remodeling

Molecular Function

phosphatidylserine binding
phospholipid transporter activity
oxysterol binding
lipid binding
sterol transporter activity

Cellular Component

endoplasmic reticulum membrane
cytosol
membrane
integral component of membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263650
Coding exons: 21
Length: 79624
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125695
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.665	500	544	0.920	0.0000364	5603
Missense (PolyPhen)		165	212.32	0.77712		2164
Synonymous	0.730	234	249	0.941	0.0000182	1747
Loss of Function	4.02	18	48.1	0.374	0.00000248	525

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0.00019	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00023	0.00023	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:23934110, PubMed:26206935). May cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes (PubMed:21220512). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:21220512, ECO:0000269|PubMed:23934110, ECO:0000269|PubMed:26206935}.;

Recessive Scores

pRec: 0.0928

Intolerance Scores

LoFtool: 0.695
RVIS EVS: -0.52
RVIS percentile EVS: 20.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.856

Gene Damage Prediction

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