LOXHD1

Chr 18

lipoxygenase homology PLAT domains 1

Also known as: DFNB77, LH2D1

This gene encodes a highly conserved protein consisting entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains, thought to be involved in targeting proteins to the plasma membrane. Studies in mice show that this gene is expressed in the mechanosensory hair cells in the inner ear, and mutations in this gene lead to auditory defects, indicating that this gene is essential for normal hair cell function. Screening of human families segregating deafness identified a mutation in this gene which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 77

Clinical highlights

Gene-disease validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
19
Pubs (1 yr)
P/LP submissions
P/LP missense
1.01
LOEUF
LOF
Mechanism· G2P
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GeneReview available — LOXHD1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.01LOEUF
pLI 0.000
Z-score 1.47
OE 0.79 (0.621.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
1.38Z-score
OE missense 0.85 (0.790.91)
577 obs / 678.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.79 (0.621.01)
00.351.4
Missense OE?0.85 (0.790.91)
00.61.4
Synonymous OE?0.88
01.21.6
LoF obs/exp: 46 / 58.1Missense obs/exp: 577 / 678.0Syn Z: 1.61

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LOXHD1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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