LHFPL6

Chr 13

LHFPL tetraspan subfamily member 6

Also known as: LHFP

NCBI Gene: 10186 ENSG00000183722 UniProt: Q9Y693

LHFPL6 encodes a tetraspan transmembrane protein that is part of the lipoma HMGIC fusion partner gene family. Mutations cause autosomal recessive nonsyndromic hearing loss, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.601), consistent with its essential role in auditory function.

ResearchSummary from RefSeq

This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. This gene is fused to a high-mobility group gene in a translocation-associated lipoma. Mutations in another LHFP-like gene result in deafness in humans and mice. Alternatively spliced transcript variants have been found; however, their full-length nature is not known. [provided by RefSeq, Jul 2008]

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

0.60

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.671

Z-score 2.27

OE 0.13 (0.04–0.60)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.65Z-score

OE missense 0.83 (0.70–0.98)

97 obs / 116.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.04–0.60)

0≤0.351.4

Missense OE?0.83 (0.70–0.98)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 1 / 7.9Missense obs/exp: 97 / 116.9Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in LHFPL6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

235 rare PASS variants

Rare truncating (LoF)

1 in 12,000

24 rare PASS variants

Rare synonymous (reference)

1 in 470

111 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LHFPL6. 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 510	1 in 10,000
South Asian	~43k	1 in 330	≈ 1 in 18,000
Remaining (unassigned)	~30k	1 in 210	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,400	none seen
Admixed American	~22k	1 in 280	≈ 1 in 11,000
African / African American	~21k	1 in 240	≈ 1 in 9,300
East Asian	~20k	1 in 830	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 180	≈ 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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓