LHFPL5

Chr 6AR

LHFPL tetraspan subfamily member 5

Also known as: DFNB67, TMHS, dJ510O8.8

LHFPL5 encodes an auxiliary subunit of the mechanotransducer channel complex at cochlear hair cell stereocilia tips that mediates auditory sensory transduction by functionally coupling PCDH15 to the transduction channel. Mutations cause autosomal recessive deafness (DFNB67), typically presenting as congenital or early-onset sensorineural hearing loss affecting the auditory system.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.431 OMIM phenotype
Clinical SummaryLHFPL5
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.000
Z-score 0.72
OE 0.73 (0.401.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.30Z-score
OE missense 0.93 (0.801.08)
124 obs / 133.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.401.43)
00.351.4
Missense OE0.93 (0.801.08)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 6 / 8.2Missense obs/exp: 124 / 133.8Syn Z: 1.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongLHFPL5-related deafnessLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7230th %ile
GOF
0.75top 25%
LOF
0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LHFPL5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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