OSBPL11

Chr 3

oxysterol binding protein like 11

Also known as: ORP-11, ORP11, OSBP12, TCCCIA00292

NCBI Gene: 114885 ENSG00000144909 UniProt: Q9BXB4 OMIM: 606739

The encoded protein is a lipid transfer protein that exchanges phosphatidylserine and phosphatidylinositol-4-phosphate between the endoplasmic reticulum and Golgi complex, which is essential for sphingomyelin synthesis. Mutations cause autosomal recessive congenital ichthyosis, a disorder affecting skin barrier function present from birth. The gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.36

LOEUF

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.36LOEUF

pLI 0.834

Z-score 4.55

OE 0.19 (0.11–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.29Z-score

OE missense 0.68 (0.61–0.75)

272 obs / 401.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.11–0.36)

0≤0.351.4

Missense OE?0.68 (0.61–0.75)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 7 / 36.7Missense obs/exp: 272 / 401.3Syn Z: 0.80

Background carrier burden — how many people carry a rare variant somewhere in OSBPL11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 94

780 rare PASS variants

Rare truncating (LoF)

1 in 4,900

69 rare PASS variants

Rare synonymous (reference)

1 in 190

299 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OSBPL11. 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 110	1 in 4,500
South Asian	~43k	1 in 79	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 80	1 in 1,000
European (Finnish)	~27k	1 in 630	none seen
Admixed American	~22k	1 in 84	1 in 1,600
African / African American	~21k	1 in 100	1 in 3,500
East Asian	~20k	1 in 110	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 310	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	≈ 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): 11 of 13 coding exons well covered in gnomAD exomes; exons 2, 4 marginal. Genomes: 12 of 13 (exon 5 below).? see exons ↓