OSBPL6

Chr 2

oxysterol binding protein like 6

Also known as: ORP6

NCBI Gene: 114880 ENSG00000079156 UniProt: Q9BZF3 OMIM: 606734

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. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.20

Clinical Summary— OSBPL6

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

122 VUS of 138 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 6.36

OE 0.10 (0.06–0.20)

Highly constrained

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

Missense Constraint?

1.78Z-score

OE missense 0.78 (0.72–0.85)

413 obs / 528.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.06–0.20)

0≤0.351.4

Missense OE?0.78 (0.72–0.85)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 6 / 58.5Missense obs/exp: 413 / 528.1Syn Z: 1.10

This gene — mechanism propensity

0.4190th %ile

GOF

0.4776th %ile

LOF

0.68top 25%

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

LOFprediction above median · LOEUF 0.20

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

138 submitted variants in ClinVar

ClinVar

Classification Summary

VUS122

Likely Benign4

122

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	122	0	0	122
Likely Benign	2	1	1	4
Benign	0	0	0	0
Total	124	1	1	126

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap OSBPL6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →