OSBPL10

Chr 3

oxysterol binding protein like 10

The protein functions as a lipid transporter that exchanges phosphatidylserine and phosphatidylinositol 4-phosphate between the endoplasmic reticulum and plasma membrane, and negatively regulates lipid biosynthesis. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.696).

ResearchSummary from RefSeq, UniProt

Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable) (PubMed:23934110). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Interacts with OSBPL9 to function as lipid transfer proteins (PubMed:36853333). Together they form a heterodimer that localizes at the ER-trans-Golgi membrane contact sites, and exchanges phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) for phosphatidylinositol-4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), PI(4)P) between the two organelles, a step that is critical for sphingomyelin synthesis in the Golgi complex (PubMed:36853333). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110)

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.000

Z-score 3.01

OE 0.46 (0.32–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.87Z-score

OE missense 0.88 (0.81–0.96)

369 obs / 419.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.32–0.70)

0≤0.351.4

Missense OE?0.88 (0.81–0.96)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 17 / 36.6Missense obs/exp: 369 / 419.1Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in OSBPL10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

1,052 rare PASS variants

Rare truncating (LoF)

1 in 1,000

135 rare PASS variants

Rare synonymous (reference)

1 in 71

483 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OSBPL10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 87	1 in 1,700
South Asian	~43k	1 in 63	1 in 1,300
Remaining (unassigned)	~30k	1 in 65	1 in 670
European (Finnish)	~27k	1 in 240	1 in 660
Admixed American	~22k	1 in 56	1 in 1,400
African / African American	~21k	1 in 70	1 in 660
East Asian	~20k	1 in 55	1 in 650
Ashkenazi Jewish	~13k	1 in 210	1 in 1,800
Middle Eastern	~2,884	1 in 59	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓