LOXHD1

lipoxygenase homology PLAT domains 1

Basic information

Region (hg38): 18:46476971-46657220

Previous symbols: [ "DFNB77" ]

Links

ENSG00000167210 ∙ NCBI:125336 ∙ OMIM:613072 ∙ HGNC:26521 ∙ Uniprot:Q8IVV2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 77 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Fuchs' endothelial dystrophy (Limited), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 77 (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 77	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	19732867; 23226338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LOXHD1 gene.

• not provided (1712 variants)
• Autosomal recessive nonsyndromic hearing loss 77 (470 variants)
• not specified (298 variants)
• Inborn genetic diseases (128 variants)
• Hearing impairment (14 variants)
• Rare genetic deafness (11 variants)
• Nonsyndromic genetic hearing loss (10 variants)
• Nonsyndromic Hearing Loss, Recessive (5 variants)
• LOXHD1-related condition (3 variants)
• Deafness (1 variants)
• Hearing loss, autosomal recessive (1 variants)
• Stickler syndrome (1 variants)
• Variant of unknown significance (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LOXHD1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	731	5	744
missense		4	423	21	4	452
nonsense	65	30				95
start loss	1		1	1		3
frameshift	74	21	1			96
inframe indel			7	1	1	9
splice donor/acceptor (+/-2bp)	6	69	1			76
splice region			13	125	3	141
non coding	1		20	171	56	248
Total	147	124	461	925	66

Highest pathogenic variant AF is 0.0000526

Variants in LOXHD1

This is a list of pathogenic ClinVar variants found in the LOXHD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-46477048-T-G			Benign (May 13, 2021)
18-46477188-C-T		not specified • LOXHD1-related disorder	Benign/Likely benign (May 01, 2023)
18-46477200-C-A		not specified	Uncertain significance (Jun 11, 2013)
18-46477348-T-C		Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (Jan 13, 2018)
18-46477376-C-T		Autosomal recessive nonsyndromic hearing loss 77	Conflicting classifications of pathogenicity (Sep 05, 2018)
18-46477378-A-G		Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (Jan 13, 2018)
18-46477399-T-A		Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (Jan 13, 2018)
18-46477453-G-A		Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (Jan 13, 2018)
18-46477468-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (May 04, 2015)
18-46477482-G-A		Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (Jul 19, 2017)
18-46477500-G-A			Uncertain significance (Jan 28, 2023)
18-46477502-G-A			Likely benign (Jan 20, 2024)
18-46477511-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 77	Conflicting classifications of pathogenicity (Jan 29, 2024)
18-46477514-C-G			Likely benign (Apr 25, 2022)
18-46477514-C-T			Likely benign (Oct 06, 2021)
18-46477515-C-G		Autosomal recessive nonsyndromic hearing loss 77	Uncertain significance (Jun 04, 2022)
18-46477516-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
18-46477517-C-T		Autosomal recessive nonsyndromic hearing loss 77	Likely benign (Dec 16, 2023)
18-46477523-G-A			Likely benign (Feb 18, 2021)
18-46477527-A-G		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
18-46477531-A-G			Uncertain significance (Feb 01, 2024)
18-46477535-G-A			Likely benign (Dec 31, 2022)
18-46477543-T-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
18-46477544-G-A			Likely benign (Oct 14, 2021)
18-46477550-G-T			Likely benign (Apr 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LOXHD1	protein_coding	protein_coding	ENST00000300591	22	180062

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.59e-26	0.0322	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	577	678	0.851	0.0000418	7398
Missense in Polyphen		351	432.11	0.8123		4862
Synonymous	1.61	245	279	0.878	0.0000194	2061
Loss of Function	1.47	46	58.1	0.792	0.00000314	621

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in hearing. Required for normal function of hair cells in the inner ear (By similarity). {ECO:0000250, ECO:0000269|PubMed:19732867}.
• Disease: DISEASE: Deafness, autosomal recessive, 77 (DFNB77) [MIM:613079]: A form of non-syndromic deafness characterized by preserved low- frequency hearing, and a trend toward mild to moderate mid- frequency and high-frequency hearing loss during childhood and adolescence. Hearing loss progresses to become moderate to severe at mid and high frequencies during adulthood. {ECO:0000269|PubMed:19732867}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.100

Intolerance Scores

• rvis_EVS: 1.18
• rvis_percentile_EVS: 92.83

Haploinsufficiency Scores

• pHI: 0.176
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.868

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Loxhd1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: sensory perception of sound;oxidation-reduction process;cellular oxidant detoxification
• Cellular component: stereocilium
• Molecular function: catalase activity;heme binding