TECTA

Summary

TECTA (tectorin alpha, HGNC:11720) is a protein-coding gene on chromosome 11q23.3, encoding Alpha-tectorin (O75443). One of the major non-collagenous components of the tectorial membrane.

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness.

Source: NCBI Gene 7007 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 125 total — 10 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 3
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_005422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11720
Approved symbol	TECTA
Name	tectorin alpha
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109927
Ensembl biotype	protein_coding
OMIM	602574
Entrez	7007

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264037, ENST00000392793, ENST00000478058, ENST00000642222, ENST00000645008, ENST00000646278

RefSeq mRNA: 2 — MANE Select: NM_005422 NM_001378761, NM_005422

CCDS: CCDS8434

Canonical transcript exons

ENST00000392793 — 24 exons

Exon	Start	End
ENSE00000748785	121105831	121105964
ENSE00000748790	121125302	121125872
ENSE00000748791	121127752	121128344
ENSE00000748792	121129638	121130211
ENSE00000748800	121162075	121162370
ENSE00000748802	121165273	121165383
ENSE00000748804	121166578	121166780
ENSE00000748806	121168054	121168217
ENSE00000748808	121168677	121168925
ENSE00000748811	121187832	121187994
ENSE00000748813	121189080	121189167
ENSE00000748815	121189764	121189880
ENSE00000990495	121109211	121109498
ENSE00000990497	121113072	121113209
ENSE00000990499	121113553	121113718
ENSE00000990501	121118306	121118718
ENSE00000990505	121137421	121138022
ENSE00000990507	121145555	121146116
ENSE00000990509	121152881	121153080
ENSE00000990511	121157841	121158224
ENSE00000990512	121160135	121160421
ENSE00001513130	121190706	121191490
ENSE00001513132	121102665	121102729
ENSE00001513133	121101243	121101442

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 97.57.

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.57	gold quality
secondary oocyte	CL:0000655	95.96	gold quality
parotid gland	UBERON:0001831	82.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.64	gold quality
buccal mucosa cell	CL:0002336	77.40	gold quality
sperm	CL:0000019	76.05	silver quality
vena cava	UBERON:0004087	74.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.15	gold quality
male germ cell	CL:0000015	73.93	gold quality
tendon of biceps brachii	UBERON:0008188	72.56	gold quality
cerebellar vermis	UBERON:0004720	72.25	gold quality
substantia nigra pars reticulata	UBERON:0001966	71.75	silver quality
subthalamic nucleus	UBERON:0001906	71.54	gold quality
myocardium	UBERON:0002349	71.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	70.92	silver quality
parietal lobe	UBERON:0001872	70.87	silver quality
postcentral gyrus	UBERON:0002581	70.87	silver quality
superior frontal gyrus	UBERON:0002661	70.80	gold quality
body of tongue	UBERON:0011876	70.72	gold quality
superior vestibular nucleus	UBERON:0007227	70.61	silver quality
cortical plate	UBERON:0005343	70.23	gold quality
substantia nigra pars compacta	UBERON:0001965	69.85	silver quality
pons	UBERON:0000988	69.84	silver quality
Brodmann (1909) area 23	UBERON:0013554	69.76	silver quality
pericardium	UBERON:0002407	69.53	gold quality
lateral globus pallidus	UBERON:0002476	69.24	gold quality
saphenous vein	UBERON:0007318	69.23	gold quality
pylorus	UBERON:0001166	69.16	gold quality
tongue	UBERON:0001723	68.71	gold quality
ventricular zone	UBERON:0003053	68.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.69

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 33)

• cysteine substitution in the zona pellucida domain of alpha-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family (PMID:11333869)
• distinctive phenotype associated with homozygosity for two novel frameshift mutations (649insC and 6037delG) of TECTA cosegregating with hearing loss linked to DFNB21 (PMID:12746400)
• A nucleotide change in exon 13, 4526T>G, was detected leading to a substitution from cysteine to glycine at codon 1509 of the TECTA protein and causing hearing impairment. (PMID:15319541)
• The presently identified mutation affecting the zona pellucida (ZP) domain resulted in a substantially lesser degree of hearing impairment than was previously reported for DFNA8/12 traits with mutations affecting the ZP domain of alpha-tectorin. (PMID:16718611)
• the sensorineural hearing impairment in TECTA mutations may be characterized as a cochlear conductive hearing impairment (PMID:17136632)
• Study described six TECTA mutations in autosomal recessive nonsyndromic hearing loss Iranian families (PMID:17431902)
• Identification of a p.Cys1837Arg autosomal dominant mutation in alpha-tectorin segregating in family members with non-syndromic hearing loss. (PMID:17661817)
• In this study, seventy-five Iranian families segregating autosomal recessive non-syndromic hearing impairment were analyzed. By sequencing all 23 coding exons of TECTA, a frameshift mutation was found. (PMID:18022253)
• Mid-frequency DFNA8/12 hearing loss caused by a synonymous TECTA mutation. (PMID:18575463)
• A single nucleotide mutation in a Dutch family caused nonsyndromic autosomal dominant sensorineural hearing impairmentm (PMID:19005249)
• The tectorial membrane was shortened in heterozygous Tecta(C1509G/+) mice, reaching only the first row of outer hair cells. (PMID:20142329)
• Mutation analysis of the TECTA gene was performed in 62 Korean patients with hereditary hearing loss. (PMID:20947814)
• data identify CEACAM16 as an alpha-tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia and, when mutated, results in ADNSHL at the DFNA4 locus (PMID:21368133)
• mutations in the N-terminal region of alpha-tectorin lead to mid-frequency nonsyndromic hearing loss (PMID:21520338)
• Here, we identified a missense mutation (p.C1691F) and a splicing mutation (c.6162+3insT), one in each TECTA allele, in the patient with hearing loss. (PMID:22037481)
• CEACAM16 can probably form higher order structures with other tectorial membrane proteins such as alpha-tectorin and beta-tectorin and influences the physical properties of the tectorial membrane (PMID:22544735)
• we have reported the prevalence of TECTA mutations in Japanese autosomal dominant nonsyndromic hearing loss (ADNSHL) patients detected by genetic screening, and confirmed the genotype-phenotype correlations. (PMID:22718023)
• this study failed to replicate a GWAS reporting an association between the 2 SNPs rs2296308 in RWDD3 and rs1829 in the intron of TECTA and time to neuropathy in ovarian cancer patients treated with paclitaxel (PMID:22877241)
• analysis allowed us to identify an aberrant transcript with skipping of exon 16, without affecting the reading frame. One of the dominant TECTA mutations already described, a synonymous substitution in exon 16 (PMID:22995349)
• Data indicate that sequencing of candidate gene TECTA (alpha-tectorin) revealed a heterozygous c.5945C>A substitution in exon 19, causing amino acid substitution of Ala to Asp at a conservative position 1982. (PMID:23936151)
• Identified the c.211delC mutation in the KCNQ4 gene and the c.2967C>A (p.H989Q) mutation in the TECTA gene to be associated with high-frequency sensorineural hearing loss in a Japanese family. (PMID:24655070)
• Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. (PMID:24816743)
• A rare novel mutation in TECTA causes autosomal dominant nonsyndromic hearing loss in a Mongolian family. (PMID:25008054)
• Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. (PMID:25413827)
• the present report suggest that the association of RWDD3 and TECTA with paclitaxel-induced peripheral neuropathy may have been a false positive signal (PMID:25549536)
• Up to now, merely 7 loci have been linked to mid-frequency hearing loss. Only four genetic mid-frequency deafness genes, namely, DFNA10 (EYA4), DFNA8/12 (TECTA), DFNA13 (COL11A2), DFNA44 (CCDC50), have been reported to date. [review] (PMID:27142990)
• To our knowledge, this is the first reported TECTA mutation leading to the DFNB21 form of hearing impairment among Maghrebian individuals suffering from congenital hearing impairment (PMID:27368438)
• A novel homozygous variant (c.734G > A) was found in exon 5 of the TECTA gene in one family leading to a nonsense mutation causing autosomal recessive nonsyndromic hearing loss. (PMID:28012541)
• TECTA mutations were identified in 6.0% of mid-frequency sensorineural hearing loss cases; these mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive. (PMID:28946916)
• homozygous c.1893C>A mutation of the TECTA gene probably underlies the proband’s hearing loss which conformed to an autosomal recessive inheritance (PMID:30703234)
• A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations. (PMID:32382995)
• Next-Generation Sequencing Identifies Pathogenic Variants in HGF, POU3F4, TECTA, and MYO7A in Consanguineous Pakistani Deaf Families. (PMID:33976695)
• Characterization of a possible founder synonymous variant in TECTA in multiple individuals with autosomal recessive hearing loss. (PMID:35870179)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tecta	ENSDARG00000059558
mus_musculus	Tecta	ENSMUSG00000037705
rattus_norvegicus	Tecta	ENSRNOG00000031126

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Alpha-tectorin — O75443 (reviewed: O75443)

All UniProt accessions (3): O75443, A0A2R8YDL0, A0A2R8YGQ5

UniProt curated annotations — full annotation on UniProt →

Function. One of the major non-collagenous components of the tectorial membrane. The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals.

Subunit / interactions. May form homomeric filament after self-association or heteromeric filament after association with beta-tectorin. Interacts with CEACAM16.

Subcellular location. Cell membrane. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. The presence of a hydrophobic C-terminus preceded by a potential cleavage site strongly suggests that tectorins are synthesized as glycosylphosphatidylinositol-linked, membrane-bound precursors. Tectorins are targeted to the apical surface of the inner ear epithelia by the lipid and proteolytically released into the extracellular compartment.

Disease relevance. Deafness, autosomal dominant, 12 (DFNA12) [MIM:601543] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal recessive, 21 (DFNB21) [MIM:603629] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Zona pellucida domain may enable to form filaments.

RefSeq proteins (2): NP_001365690, NP_005413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001007	VWF_dom	Domain
IPR001507	ZP_dom	Domain
IPR001846	VWF_type-D	Domain
IPR002919	TIL_dom	Domain
IPR003886	NIDO_dom	Domain
IPR014853	VWF/SSPO/ZAN-like_Cys-rich_dom	Domain
IPR017977	ZP_dom_CS	Conserved_site
IPR025615	TILa_dom	Domain
IPR036084	Ser_inhib-like_sf	Homologous_superfamily
IPR042235	ZP-C_dom	Homologous_superfamily
IPR052749	Alpha-tectorin	Family
IPR055355	ZP-C	Domain

Pfam: PF00094, PF00100, PF01826, PF06119, PF08742, PF12714

UniProt features (98 total): sequence variant 39, glycosylation site 30, disulfide bond 15, domain 10, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75443-F1	77.64	0.19

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2091

Disulfide bonds (15): 322–461, 344–499, 713–849, 1100–1241, 1122–1277, 1487–1622, 1509–1665, 1717–1775, 1741–1784, 1786–1818, 1806–1898, 1837–1857, 1980–2040, 2001–2056, 2045–2052

Glycosylation sites (30): 34, 187, 215, 278, 455, 506, 528, 560, 670, 687, 813, 843, 855, 898, 920, 931, 949, 1048, 1235, 1364 …

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 105 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, AREB6_03, GOBP_NEUROGENESIS, LHX3_01, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, TGACATY_UNKNOWN, GOBP_EAR_MORPHOGENESIS, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_AUDITORY_RECEPTOR_CELL_DEVELOPMENT

GO Biological Process (3): cell-matrix adhesion (GO:0007160), sensory perception of sound (GO:0007605), auditory receptor cell stereocilium organization (GO:0060088)

GO Molecular Function (2): extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
cell-substrate adhesion	1
sensory perception of mechanical stimulus	1
auditory receptor cell morphogenesis	1
inner ear receptor cell stereocilium organization	1
structural molecule activity	1
extracellular matrix	1
binding	1
cell periphery	1
external encapsulating structure	1
extracellular vesicle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1127 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TECTA	OTOA	Q7RTW8	930
TECTA	CEACAM16	Q2WEN9	902
TECTA	COCH	O43405	783
TECTA	TECTB	Q96PL2	695
TECTA	OTOL1	A6NHN0	676
TECTA	STRC	Q7RTU9	661
TECTA	GJB2	P29033	644
TECTA	MUC2	Q02817	602
TECTA	OTOS	Q8NHW6	592
TECTA	OTOG	Q6ZRI0	572
TECTA	MYO15A	Q9UKN7	553
TECTA	OTOGL	Q3ZCN5	529
TECTA	COL11A2	P13942	526
TECTA	SLC26A4	O43511	500
TECTA	OTOF	Q9HC10	497

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
TECTA	ZBTB43	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): TECTA (Affinity Capture-RNA), TECTA (Affinity Capture-MS), TECTA (Affinity Capture-MS), ZBTB43 (Affinity Capture-MS), ZIC2 (Affinity Capture-MS), PGAP1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Y0, F7A4A7, O08523, O55225, O75443, O77780, P59510, P82279, P98089, P98092, Q0V8S9, Q0V8T0, Q0V8T3, Q0V8T4, Q0V8T5, Q0V8T6, Q0V8T7, Q0V8T8, Q0V8T9, Q29RU2, Q3ZCN5, Q5RCW9, Q5RD64, Q60411, Q62635, Q6DFV8, Q6PZE0, Q6V0K7, Q6ZRI0, Q80Z19, Q8CFM6, Q8CIZ8, Q8CJ69, Q8N2E2, Q8N8U9, Q8R4U0, Q8R4V5, Q8R4Y4, Q8VHS2, Q8WWQ8

Diamond homologs: A1Z877, O08523, O75443, O75581, O88572, P01131, P20063, P35950, P35951, P35952, Q14114, Q28832, Q5ZQU0, Q6X0I2, Q70E20, Q8TER0, Q91VN0, Q98931, Q99087, Q9JI18, Q9NZR2, Q9YH85, A0A1D0C023, A2ARV4, B3EWY9, B3NBB6, B4HVU2, B4PD96, B5DFC9, F1RRV3, O08710, O42182, O73775, O75095, O75197, O77469, O88322, P01130, P01266, P01267

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

125 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	9
Uncertain significance	58
Likely benign	3
Benign	7

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1334118	NM_005422.4(TECTA):c.1705C>T (p.Gln569Ter)	Pathogenic
179381	NM_005422.4(TECTA):c.327C>T (p.Gly109=)	Pathogenic
2176757	NM_005422.4(TECTA):c.3520C>T (p.Arg1174Ter)	Pathogenic
3601870	NM_005422.4(TECTA):c.3013del (p.Leu1005fs)	Pathogenic
3601871	NM_005422.4(TECTA):c.3060_3061insAAGAGTCTGAACCAAGGGAGGAGCAGTGGCGTGGAAAGGGTTGTCAGCTAAGA (p.Glu1021delinsLysSerLeuAsnGlnGlyArgSerSerGlyValGluArgValValSerTer)	Pathogenic
402279	NM_005422.4(TECTA):c.4857C>A (p.Cys1619Ter)	Pathogenic
498538	NM_005422.4(TECTA):c.4085G>A (p.Trp1362Ter)	Pathogenic
627480	NM_005422.4(TECTA):c.5866C>T (p.Arg1956Ter)	Pathogenic
7020	NM_005422.4(TECTA):c.5509T>G (p.Cys1837Gly)	Pathogenic
7023	NM_005422.4(TECTA):c.5509T>C (p.Cys1837Arg)	Pathogenic
1799538	NM_005422.4(TECTA):c.2458A>T (p.Lys820Ter)	Likely pathogenic
3075725	NM_005422.4(TECTA):c.568A>C (p.Thr190Pro)	Likely pathogenic
3075938	NM_005422.4(TECTA):c.12dup (p.Ser5fs)	Likely pathogenic
3250403	NM_005422.4(TECTA):c.1301G>T (p.Gly434Val)	Likely pathogenic
3250404	NM_005422.4(TECTA):c.2614G>T (p.Ala872Ser)	Likely pathogenic
3375234	NM_005422.4(TECTA):c.2367+2T>C	Likely pathogenic
4687905	NM_005422.4(TECTA):c.1734dup (p.Gly579fs)	Likely pathogenic
7024	NM_005422.4(TECTA):c.5331G>A (p.Leu1777=)	Likely pathogenic
869465	NM_005422.4(TECTA):c.5539T>C (p.Ser1847Pro)	Likely pathogenic

SpliceAI

4130 predictions. Top by Δscore:

Variant	Effect	Δscore
11:121109401:GGAA:G	donor_gain	1.0000
11:121109402:G:T	donor_gain	1.0000
11:121109402:GAAG:G	donor_gain	1.0000
11:121109405:G:GG	donor_gain	1.0000
11:121109463:G:GT	donor_gain	1.0000
11:121109499:G:GG	donor_gain	1.0000
11:121113656:GCCGC:G	donor_gain	1.0000
11:121113681:A:T	donor_gain	1.0000
11:121113685:G:GT	donor_gain	1.0000
11:121113686:A:T	donor_gain	1.0000
11:121113716:GGG:G	donor_gain	1.0000
11:121113717:GGG:G	donor_gain	1.0000
11:121146117:G:GG	donor_gain	1.0000
11:121152879:A:AG	acceptor_gain	1.0000
11:121152880:G:GT	acceptor_gain	1.0000
11:121152880:GCT:G	acceptor_gain	1.0000
11:121158220:TCA:T	donor_gain	1.0000
11:121158220:TCAAG:T	donor_loss	1.0000
11:121158221:CAAG:C	donor_loss	1.0000
11:121158222:AAG:A	donor_gain	1.0000
11:121158225:GTA:G	donor_loss	1.0000
11:121158226:T:G	donor_loss	1.0000
11:121160132:TAG:T	acceptor_loss	1.0000
11:121160133:A:C	acceptor_loss	1.0000
11:121160134:G:GA	acceptor_loss	1.0000
11:121160134:GGT:G	acceptor_gain	1.0000
11:121162064:A:AG	acceptor_gain	1.0000
11:121162065:G:GG	acceptor_gain	1.0000
11:121162368:GCT:G	donor_gain	1.0000
11:121162371:G:GG	donor_gain	1.0000

AlphaMissense

14299 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:121105891:A:T	D42V	1.000
11:121105894:A:C	D43A	1.000
11:121105894:A:T	D43V	1.000
11:121109222:C:A	N70K	1.000
11:121109222:C:G	N70K	1.000
11:121109310:T:A	W100R	1.000
11:121109310:T:C	W100R	1.000
11:121109457:T:A	W149R	1.000
11:121109457:T:C	W149R	1.000
11:121125853:G:C	W585C	1.000
11:121125853:G:T	W585C	1.000
11:121130038:T:G	F923C	1.000
11:121130192:G:C	W974C	1.000
11:121130192:G:T	W974C	1.000
11:121137777:T:C	C1100R	1.000
11:121146097:G:C	W1362C	1.000
11:121146097:G:T	W1362C	1.000
11:121153051:G:T	G1426C	1.000
11:121157858:G:C	W1441C	1.000
11:121157858:G:T	W1441C	1.000
11:121160396:T:A	W1651R	1.000
11:121160396:T:C	W1651R	1.000
11:121160398:G:C	W1651C	1.000
11:121160398:G:T	W1651C	1.000
11:121162351:G:C	W1751C	1.000
11:121162351:G:T	W1751C	1.000
11:121168159:T:C	C1898R	1.000
11:121168864:T:C	C1980R	1.000
11:121105890:G:C	D42H	0.999
11:121105890:G:T	D42Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000068377 (11:121102429 A>G), RS1000187632 (11:121145914 C>T), RS1000212324 (11:121135008 T>C), RS1000263239 (11:121135084 C>T), RS1000293636 (11:121180956 A>G), RS1000310945 (11:121137746 G>C), RS1000338319 (11:121167899 G>A,T), RS1000346994 (11:121174759 A>C,G), RS1000363912 (11:121138021 T>C), RS1000411975 (11:121170956 T>C,G), RS1000424012 (11:121174895 C>T), RS1000562128 (11:121119140 C>A,T), RS1000572422 (11:121143908 C>A), RS1000578470 (11:121149167 C>A), RS1000630041 (11:121108961 G>T)

Disease associations

OMIM: gene MIM:602574 | disease phenotypes: MIM:601543, MIM:603629, MIM:156000, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 12	Strong	Autosomal dominant
autosomal recessive nonsyndromic hearing loss 21	Strong	Autosomal recessive
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AR
nonsyndromic genetic hearing loss	Definitive	AD

Mondo (6): autosomal dominant nonsyndromic hearing loss 12 (MONDO:0011102), autosomal recessive nonsyndromic hearing loss 21 (MONDO:0011351), Meniere disease (MONDO:0007972), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (5): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare non-syndromic genetic deafness (Orphanet:87884), Rare genetic deafness (Orphanet:96210), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005549_17	Alzheimer’s disease (late onset)	1.000000e-07
GCST007673_15	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0009603	stroke outcome severity measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008575	Meniere Disease	C09.218.568.217.500
C563295	Deafness, Autosomal Dominant 12 (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C566353	Deafness, Autosomal Recessive 21 (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, decreases expression	3
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2-methyl-4-isothiazolin-3-one	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AV04	Chor-IN-1	Cancer cell line	Male

Clinical trials (associated diseases)

32 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids
NCT05844657	Not specified	COMPLETED	Comprehensive Evaluation in Patients With Meniere’s Disease
NCT05960786	Not specified	COMPLETED	Treating the Symptoms of Vertigo in a Real-world Setting Using the OtoBand
NCT06278129	Not specified	UNKNOWN	Evaluation of the Diagnostic and Prognostic Efficacy of MRI in Acute Sensorineural Hearing Loss and Ménière’s Disease
NCT06544590	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease