OSBPL9

Chr 1

oxysterol binding protein like 9

Also known as: ORP-9, ORP9

NCBI Gene: 114883 ENSG00000117859 UniProt: Q96SU4 OMIM: 606737

The protein functions as a cholesterol transfer protein that regulates Golgi structure and exchanges phosphatidylserine for phosphatidylinositol-4-phosphate between the endoplasmic reticulum and trans-Golgi, which is critical for sphingomyelin synthesis. This gene is highly constrained against loss-of-function variants (pLI = 0.98, LOEUF = 0.31), but no established human disease has been definitively associated with OSBPL9 mutations to date.

OMIM ResearchSummary from RefSeq, UniProt

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. This family member functions as a cholesterol transfer protein that regulates Golgi structure and function. Multiple transcript variants, most of which encode distinct isoforms, have been identified. Related pseudogenes have been identified on chromosomes 3, 11 and 12. [provided by RefSeq, Jul 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.31

Clinical Summary— OSBPL9

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

70 VUS of 96 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.976

Z-score 5.25

OE 0.17 (0.10–0.31)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.66Z-score

OE missense 0.62 (0.56–0.69)

246 obs / 394.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.31)

0≤0.351.4

Missense OE?0.62 (0.56–0.69)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 8 / 46.7Missense obs/exp: 246 / 394.4Syn Z: 0.69

This gene — mechanism propensity

0.3792th %ile

GOF

0.4874th %ile

LOF

0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	70	70
Likely Benign	0	0
Benign	0	0
Total	70	70

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap OSBPL9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →