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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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LOXHD1
lipoxygenase homology PLAT domains 1
Chromosome 18 Β· 18q21.1
NCBI Gene: 125336Ensembl: ENSG00000167210.17HGNC: HGNC:26521UniProt: A0A2R8Y7K4
27PubMed Papers
21Diseases
0Drugs
443Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sensory perception of soundstereociliumhearing loss, autosomal recessivedeafnessnonsyndromic genetic hearing lossautosomal dominant nonsyndromic hearing loss
✦AI Summary

LOXHD1 (lipoxygenase homology PLAT domains 1) is essential for normal hearing function, primarily through its role in maintaining auditory mechanotransduction in inner ear hair cells. LOXHD1 is indispensable for localizing and stabilizing TMC1, the pore-forming subunit of mechanosensitive ion channels at the stereocilial tip link, the site where sound-induced forces are transmitted 1. It selectively interacts with TMC1, CIB2, LHFPL5, and the tip-link protein PCDH15 to maintain functional mature auditory channels, though it is dispensable for the developmental TMC2-driven channels 1. Mutations in LOXHD1 cause autosomal recessive deafness (DFNB77), with LOXHD1 variants accounting for 33.3% of genetically diagnosed down-sloping sensorineural hearing loss cases in young adults, emerging as a signature causative gene in this population 2. LOXHD1 has been identified as a promising candidate for gene therapy approaches to hearing loss 3, offering potential clinical intervention for genetic deafness. Outside the auditory system, LOXHD1 shows restricted expression in the testis and serves as an oncofusion-regulated tumor-associated antigen in Ewing sarcoma 4. While LOXHD1 variants have been reported in Fuchs corneal dystrophy studies, its causal pathogenic role in corneal disease remains unconfirmed 5.

Sources cited
1
LOXHD1 is essential for maintaining TMC1 localization at the tip link and keeping mechanotransduction channels functional
PMID: 39256406
2
LOXHD1 accounts for 33.3% of genetically diagnosed down-sloping SNHL cases and 12.8% of the whole young adult down-sloping SNHL cohort
PMID: 33753533
3
LOXHD1 is identified as a promising candidate for gene therapy of hearing loss
PMID: 39951658
4
LOXHD1 shows restricted expression in inner hair cells, testis, and is aberrantly expressed in Ewing sarcoma
PMID: 40234527
5
No LOXHD1 variants were classified as pathogenic for Fuchs corneal dystrophy and LOXHD1 is not expressed in corneal endothelium
PMID: 37441688
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.74Strong
deafnessOpen Targets
0.66Moderate
nonsyndromic genetic hearing lossOpen Targets
0.63Moderate
autosomal dominant nonsyndromic hearing lossOpen Targets
0.57Moderate
Rare genetic deafnessOpen Targets
0.55Moderate
Hearing impairmentOpen Targets
0.49Moderate
genetic disorderOpen Targets
0.42Moderate
Non-syndromic genetic deafnessOpen Targets
0.39Weak
neurodegenerative diseaseOpen Targets
0.37Weak
age-related hearing impairmentOpen Targets
0.34Weak
disorder of earOpen Targets
0.34Weak
frozen shoulderOpen Targets
0.31Weak
alcohol drinkingOpen Targets
0.28Weak
acquired thrombocytopeniaOpen Targets
0.28Weak
ankylosing spondylitisOpen Targets
0.28Weak
deficiency anemiaOpen Targets
0.26Weak
liver cancerOpen Targets
0.24Weak
glomerulonephritisOpen Targets
0.24Weak
intrahepatic bile duct cancerOpen Targets
0.23Weak
deafness, aminoglycoside-inducedOpen Targets
0.09Suggestive
Deafness, autosomal recessive, 77UniProt
Pathogenic Variants443
NM_001384474.1(LOXHD1):c.760-2delLikely pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2026
NM_001384474.1(LOXHD1):c.232del (p.Gln78fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2026β†’ Residue 78
NM_001384474.1(LOXHD1):c.4480C>T (p.Arg1494Ter)Pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 77|Nonsyndromic genetic hearing loss|Inborn genetic diseases|LOXHD1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 1494
NM_001384474.1(LOXHD1):c.6182+1G>TLikely pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2026
NM_001384474.1(LOXHD1):c.2497C>T (p.Arg833Ter)Pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 77|Hearing impairment
β˜…β˜…β˜†β˜†2026β†’ Residue 833
NM_001384474.1(LOXHD1):c.4413del (p.Pro1472fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2026β†’ Residue 1472
NM_001384474.1(LOXHD1):c.2641G>A (p.Gly881Arg)Pathogenic
Nonsyndromic genetic hearing loss|not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2026β†’ Residue 881
NM_001384474.1(LOXHD1):c.4989G>A (p.Trp1663Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 1663
NM_001384474.1(LOXHD1):c.2431C>T (p.Gln811Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 811
NM_001384474.1(LOXHD1):c.1537_1538del (p.Leu513fs)Pathogenic
not provided|Rare genetic deafness|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 513
NM_001384474.1(LOXHD1):c.4714C>T (p.Arg1572Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 77|Rare genetic deafness|not provided|LOXHD1-related disorder|Deafness
β˜…β˜…β˜†β˜†2025β†’ Residue 1572
NM_001384474.1(LOXHD1):c.6074del (p.Gly2025fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 2025
NM_001384474.1(LOXHD1):c.4794_4795insTC (p.Ile1599fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 1599
NM_001384474.1(LOXHD1):c.442A>T (p.Lys148Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 77|not provided|LOXHD1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 148
NM_001384474.1(LOXHD1):c.1906del (p.Asp636fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 636
NM_001384474.1(LOXHD1):c.5974_5975del (p.Lys1991_Ser1992insTer)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025β†’ Residue 1991
NM_001384474.1(LOXHD1):c.4212+1G>APathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025
NM_001384474.1(LOXHD1):c.3061+1G>APathogenic
Hearing loss, autosomal recessive|not provided|Autosomal recessive nonsyndromic hearing loss 77|Hearing impairment|LOXHD1-related disorder
β˜…β˜…β˜†β˜†2025
NM_001384474.1(LOXHD1):c.4375+1G>TLikely pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025
NM_001384474.1(LOXHD1):c.246-2A>GPathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 77
β˜…β˜…β˜†β˜†2025
View on ClinVar β†—
Related Genes
ZNF354AShared pathway100%LRIG2Shared pathway100%LRIG1Shared pathway100%CLRN3Shared pathway100%LRIG3Shared pathway100%GRXCR2Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
20%
Lung
16%
Ovary
2%
Brain
2%
Liver
1%
Gene Interaction Network
Click a node to explore
LOXHD1ZNF354ALRIG2LRIG1CLRN3LRIG3GRXCR2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8IVV2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.90LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.80 [0.71–0.90]
RankingsWhere LOXHD1 stands among ~20K protein-coding genes
  • #12,597of 20,598
    Most Researched27
  • #120of 5,498
    Most Pathogenic Variants443 Β· top 5%
  • #8,065of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedLOXHD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
EZH1/EZH2 inhibition enhances adoptive TΒ cell immunotherapy against multiple cancer models.
PMID: 39983725
Cancer Cell Β· 2025
1.00
2
Gene Therapy for Hearing Loss: Which Genes Next?
PMID: 39951658
Otol Neurotol Β· 2025
0.90
3
Fuchs Corneal Dystrophy.
PMID: 26310151
Prog Mol Biol Transl Sci Β· 2015
0.80
4
Rising of
PMID: 33753533
J Med Genet Β· 2022
0.70
5
Systematic review of SLC4A11, ZEB1, LOXHD1, and AGBL1 variants in the development of Fuchs' endothelial corneal dystrophy.
PMID: 37441688
Front Med (Lausanne) Β· 2023
0.60