HDLBP

Chr 2

high density lipoprotein binding protein

Also known as: HBP, PRO2900, VGL

NCBI Gene: 3069 ENSG00000115677 UniProt: Q00341 OMIM: 142695

The encoded protein binds high density lipoprotein (HDL) to regulate cellular cholesterol levels and also binds RNA to induce heterochromatin formation. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and behavioral abnormalities, typically with childhood onset. This gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene binds high density lipoprotein (HDL) and may function to regulate excess cholesterol levels in cells. The encoded protein also binds RNA and can induce heterochromatin formation. [provided by RefSeq, Mar 2016]

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.15LOEUF

pLI 1.000

Z-score 6.67

OE 0.07 (0.03–0.15)

Highly constrained

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

Missense Constraint?

4.10Z-score

OE missense 0.58 (0.54–0.63)

451 obs / 771.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.15)

0≤0.351.4

Missense OE?0.58 (0.54–0.63)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 59.5Missense obs/exp: 451 / 771.3Syn Z: -0.49

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

1,339 rare PASS variants

Rare truncating (LoF)

1 in 790

149 rare PASS variants

Rare synonymous (reference)

1 in 69

650 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HDLBP. 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 55	1 in 680
South Asian	~43k	1 in 50	1 in 910
Remaining (unassigned)	~30k	1 in 47	1 in 1,000
European (Finnish)	~27k	1 in 150	1 in 980
Admixed American	~22k	1 in 66	1 in 790
African / African American	~21k	1 in 63	1 in 1,300
East Asian	~20k	1 in 45	1 in 2,800
Ashkenazi Jewish	~13k	1 in 140	1 in 2,100
Middle Eastern	~2,884	1 in 70	≈ 1 in 2,600

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.