Meniere disease

Summary

Meniere disease (MONDO:0007972) is a disease with 55 cohort genes (14 GWAS associations across 15 studies) and 31 clinical trials. The dominant Reactome pathway is Sensory processing of sound by outer hair cells of the cochlea (11 cohort genes). Top therapeutic interventions include montelukast, venlafaxine, and gadopentetate dimeglumine.

At a glance

• Cohort genes: 55
• GWAS associations: 14
• ClinVar variants: 225
• Clinical trials: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meniere disease
Mondo ID	MONDO:0007972
EFO	EFO:0006862
MeSH	D008575
OMIM	156000
Orphanet	45360
DOID	DOID:9849
ICD-11	683932278
NCIT	C185243
SNOMED CT	13445001
UMLS	C0025281
MedGen	7530
Is cancer (heuristic)	no

Also known as: Meniere disease

Data availability: 225 ClinVar variants · 14 GWAS associations (15 studies) · 2 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › auditory system disorder › inner ear disorder › vestibular disorder › peripheral vertigo › endolymphatic hydrops › Meniere disease

Subtypes (3): active cochleovestibular Meniere disease, active vestibular Meniere disease, active cochlear Meniere disease

Genetics & variants

GWAS landscape

14 GWAS associations across 15 studies. Top hits map to 9 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs80030049	3e-13	LINC02038 - LINC02026	C	2.07
rs75323670	1e-12	TRABD2B	C	3.24
rs76416960	6e-12	VPS13B	C	3.34
rs149479122	8e-12	PRDM11	C	2.27
rs979245270	2e-11	RNU6-832P - MTCO2P25	G	4.1
rs553411385	2e-11	SLC37A3	C	3.2
rs149544399	3e-11	ST3GAL1-DT - LINC03024	G	3.4
rs533941215	3e-11	CAMK1D	G	2.38
rs115058055	4e-11	LINC01088	C	2.17
rs573464148	1e-08	CTSZ - TUBB1	?
rs529699157	2e-08	BRMS1L, LINC00609	T	2.96
rs112950507	2e-08	RIMS1	T	2.01
rs141509041	2e-08	MIR548AP - LINC01584	T	1.25

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477813	Verma A	2024	2,074	448,199	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90018880	Sakaue S	2021	1,526	481,248	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90077840	Backman JD	2021	1,297	330,457	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081826	Backman JD	2021	1,297	330,457	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018660	Sakaue S	2021	1,290	177,436	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90077841	Backman JD	2021	1,091	327,961	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081827	Backman JD	2021	1,091	327,961	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90651477	Liu TY	2025	823	201,629	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90079942	Backman JD	2021	714	387,216	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083928	Backman JD	2021	714	387,216	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	10
unknown	2

Functional consequences

Consequence	Count
intron_variant	7
intergenic_variant	4
3_prime_UTR_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs80030049	3	193919064	C>A,T	0.001	intron_variant	LINC02038 - LINC02026	3e-13	Tier 4: intronic/intergenic
rs75323670	1	47846048	C>G	0.001	intron_variant	TRABD2B	1e-12	Tier 4: intronic/intergenic
rs76416960	8	99672995	C>T	0.001	intron_variant	VPS13B	6e-12	Tier 4: intronic/intergenic
rs149479122	11	45231753	C>T	0	3_prime_UTR_variant	PRDM11	8e-12	Tier 2: splice/UTR
rs979245270	7	69135249	G>A	0	intergenic_variant	RNU6-832P - MTCO2P25	2e-11	Tier 4: intronic/intergenic
rs553411385	7	140329710	C>T	0	intergenic_variant	SLC37A3	2e-11	Tier 4: intronic/intergenic
rs149544399	8	133642525	G>A,C	0	intergenic_variant	ST3GAL1-DT - LINC03024	3e-11	Tier 4: intronic/intergenic
rs533941215	10	12658341	G>A	0	intron_variant	CAMK1D	3e-11	Tier 4: intronic/intergenic
rs115058055	4	79196327	C>T	0.001	intron_variant	LINC01088	4e-11	Tier 4: intronic/intergenic
rs573464148	20	59011174	G>A		regulatory_region_variant	CTSZ - TUBB1	1e-08	Tier 3: regulatory
rs529699157	14	35908997	C>T	0.003	intron_variant	BRMS1L, LINC00609	2e-08	Tier 4: intronic/intergenic
rs112950507	6	72184885	C>A,G,T		intron_variant	RIMS1	2e-08	Tier 4: intronic/intergenic
rs141509041	15	85874859	C>A,T	0.05	intergenic_variant	MIR548AP - LINC01584	2e-08	Tier 4: intronic/intergenic

ClinVar germline variants

225 retrieved; paginated sample, class counts are floors:

142 uncertain significance, 54 conflicting classifications of pathogenicity, 12 likely benign, 6 likely pathogenic, 5 benign/likely benign, 3 pathogenic/likely pathogenic, 2 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
140608	NM_001329752.2(FAM136A):c.547C>T (p.Gln183Ter)	FAM136A	Pathogenic	criteria provided, single submitter
553231	NM_000260.4(MYO7A):c.3G>A (p.Met1Ile)	MYO7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228385	NM_001378609.3(OTOGL):c.975del (p.Leu325fs)	OTOGL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189251	NM_006005.3(WFS1):c.124C>T (p.Arg42Ter)	WFS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
829920	NM_000092.5(COL4A4):c.4522G>A (p.Gly1508Ser)	COL4A4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
438172	NM_000260.4(MYO7A):c.1849T>C (p.Ser617Pro)	MYO7A	Likely pathogenic	reviewed by expert panel
989235	NM_000260.4(MYO7A):c.4635G>A (p.Trp1545Ter)	MYO7A	Likely pathogenic	criteria provided, single submitter
1174005	NM_001649.4(SHROOM2):c.631G>A (p.Gly211Ser)	SHROOM2	Likely pathogenic	criteria provided, single submitter
437866	NM_206996.4(SPAG17):c.1069G>C (p.Asp357His)	SPAG17	Likely pathogenic	criteria provided, single submitter
1342173	NM_005422.4(TECTA):c.4422del (p.Asn1474fs)	TBCEL-TECTA	Likely pathogenic	criteria provided, single submitter
228715	NM_032119.4(ADGRV1):c.16640G>A (p.Arg5547His)	ADGRV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
46377	NM_032119.4(ADGRV1):c.7582C>T (p.Pro2528Ser)	ADGRV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216528	NM_001148.6(ANK2):c.8144C>T (p.Ser2715Phe)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264145	NM_001148.6(ANK2):c.10805G>A (p.Arg3602Gln)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3035374	NM_001177693.2(ARHGEF28):c.1982C>T (p.Ser661Phe)	ARHGEF28	Conflicting classifications of pathogenicity	no assertion criteria provided
45931	NM_022124.6(CDH23):c.3845A>G (p.Asn1282Ser)	C10orf105	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1174004	NM_022124.6(CDH23):c.6512G>A (p.Arg2171His)	CDH23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1056960	NM_001854.4(COL11A1):c.2231A>G (p.Lys744Arg)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291499	NM_001854.4(COL11A1):c.4594C>G (p.Pro1532Ala)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291535	NM_001854.4(COL11A1):c.1427G>A (p.Arg476His)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291544	NM_001854.4(COL11A1):c.698A>G (p.Tyr233Cys)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291548	NM_001854.4(COL11A1):c.328G>C (p.Gly110Arg)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1040200	NM_000092.5(COL4A4):c.3434G>A (p.Gly1145Glu)	COL4A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334702	NM_000092.5(COL4A4):c.4678C>T (p.Arg1560Cys)	COL4A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
838912	NM_000092.5(COL4A4):c.1055C>T (p.Pro352Leu)	COL4A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297291	NM_001852.4(COL9A2):c.1834G>A (p.Gly612Arg)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417900	NM_001852.4(COL9A2):c.2059A>G (p.Lys687Glu)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
311616	NM_018451.5(CPAP):c.2785A>G (p.Lys929Glu)	CPAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
140609	NM_001386795.1(DTNA):c.2224G>T (p.Val742Phe)	DTNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13262	NM_004431.5(EPHA2):c.2162G>A (p.Arg721Gln)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 86 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DTNA	Limited	Autosomal dominant	Meniere disease	5
TIMCC	Limited	Unknown	Meniere disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DTNA	Orphanet:54260	Left ventricular noncompaction
TECTA	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
TECTA	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
USH1C	Orphanet:231169	Usher syndrome type 1
USH1C	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
WFS1	Orphanet:3463	Wolfram syndrome
WFS1	Orphanet:411590	Wolfram-like syndrome
WFS1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
WFS1	Orphanet:98991	Early-onset nuclear cataract
CDH23	Orphanet:231169	Usher syndrome type 1
CDH23	Orphanet:2965	Prolactinoma
CDH23	Orphanet:314777	Familial isolated pituitary adenoma
CDH23	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CDH23	Orphanet:91347	TSH-secreting pituitary adenoma
CDH23	Orphanet:96253	Cushing disease
CACNA1D	Orphanet:324321	Sinoatrial node dysfunction and deafness
CACNA1D	Orphanet:369929	Primary hyperaldosteronism-seizures-neurological abnormalities syndrome
CAD	Orphanet:448010	CAD-CDG
PCDH15	Orphanet:231169	Usher syndrome type 1
PCDH15	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
KIF1B	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
KIF1B	Orphanet:99946	Autosomal dominant Charcot-Marie-Tooth disease type 2A1
TRIOBP	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CPAP	Orphanet:2512	Autosomal recessive primary microcephaly
CPAP	Orphanet:808	Seckel syndrome
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
LRBA	Orphanet:445018	Syndromic autoimmune enteropathy due to LRBA deficiency
CORIN	Orphanet:275555	Preeclampsia
LYST	Orphanet:167	Chédiak-Higashi syndrome
LYST	Orphanet:352723	Attenuated Chédiak-Higashi syndrome
EPS8L2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome
COL9A2	Orphanet:166002	Multiple epiphyseal dysplasia due to collagen 9 anomaly
COL9A2	Orphanet:250984	Autosomal recessive Stickler syndrome
MYH14	Orphanet:397744	MYH14-related peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
MYH14	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
FTO	Orphanet:210144	Lethal polymalformative syndrome, Boissel type
SPAG17	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
SPAG17	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
OTOGL	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
TENM3	Orphanet:98938	Colobomatous microphthalmia
ACAN	Orphanet:171866	Spondyloepimetaphyseal dysplasia, aggrecan type

Cohort genes → proteins

55 cohort genes, 53 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	55

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TIMCC	HGNC:25911	ENSG00000035141	Q96C01	Protein FAM136A	gencc,clinvar
DTNA	HGNC:3057	ENSG00000134769	Q9Y4J8	Dystrobrevin alpha	gencc,clinvar
SYNJ2	HGNC:11504	ENSG00000078269	O15056	Synaptojanin-2	clinvar
TECTA	HGNC:11720	ENSG00000109927	O75443	Alpha-tectorin	clinvar
USH1C	HGNC:12597	ENSG00000006611	Q9Y6N9	Harmonin	clinvar
WFS1	HGNC:12762	ENSG00000109501	O76024	Wolframin	clinvar
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
CACNA1D	HGNC:1391	ENSG00000157388	Q01668	Voltage-dependent L-type calcium channel subunit alpha-1D	clinvar
CAD	HGNC:1424	ENSG00000084774	P27708	Multifunctional protein CAD	clinvar
PCDH15	HGNC:14674	ENSG00000150275	Q96QU1	Protocadherin-15	clinvar
KIF1B	HGNC:16636	ENSG00000054523	O60333	Kinesin-like protein KIF1B	clinvar
TRIOBP	HGNC:17009	ENSG00000100106	Q9H2D6	TRIO and F-actin-binding protein	clinvar
CPAP	HGNC:17272	ENSG00000151849	Q9HC77	Centrosomal P4.1-associated protein	clinvar
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	clinvar
LRBA	HGNC:1742	ENSG00000198589	P50851	Lipopolysaccharide-responsive and beige-like anchor protein	clinvar
CORIN	HGNC:19012	ENSG00000145244	Q9Y5Q5	Atrial natriuretic peptide-converting enzyme	clinvar
GJD3	HGNC:19147	ENSG00000183153	Q8N144	Gap junction delta-3 protein	clinvar
THADA	HGNC:19217	ENSG00000115970	Q6YHU6	tRNA (32-2’-O)-methyltransferase regulator THADA	clinvar
OTOP2	HGNC:19657	ENSG00000183034	Q7RTS6	Proton channel OTOP2	clinvar
LYST	HGNC:1968	ENSG00000143669	Q99698	Lysosomal-trafficking regulator	clinvar
C10orf105	HGNC:20304	ENSG00000214688	Q8TEF2	Uncharacterized protein C10orf105	clinvar
EPS8L2	HGNC:21296	ENSG00000177106	Q9H6S3	Epidermal growth factor receptor kinase substrate 8-like protein 2	clinvar
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
COL9A2	HGNC:2218	ENSG00000049089	Q14055	Collagen alpha-2(IX) chain	clinvar
MYH14	HGNC:23212	ENSG00000105357	Q7Z406	Myosin-14	clinvar
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	clinvar
RABL6	HGNC:24703	ENSG00000196642	Q3YEC7	Rab-like protein 6	clinvar
SPAG17	HGNC:26620	ENSG00000155761	Q6Q759	Sperm-associated antigen 17	clinvar
OTOGL	HGNC:26901	ENSG00000165899	Q3ZCN5	Otogelin-like protein	clinvar
CLEC16A	HGNC:29013	ENSG00000038532	Q2KHT3	Protein CLEC16A	clinvar
TENM3	HGNC:29944	ENSG00000218336	Q9P273	Teneurin-3	clinvar
ARHGEF28	HGNC:30322	ENSG00000214944	Q8N1W1	Rho guanine nucleotide exchange factor 28	clinvar
ACAN	HGNC:319	ENSG00000157766	P16112	Aggrecan core protein	clinvar
AGL	HGNC:321	ENSG00000162688	P35573	Glycogen debranching enzyme	clinvar
EPHA2	HGNC:3386	ENSG00000142627	P29317	Ephrin type-A receptor 2	clinvar
FSCN2	HGNC:3960	ENSG00000186765	O14926	Fascin-2	clinvar
FPGT-TNNI3K	HGNC:42952	ENSG00000259030		FPGT-TNNI3K readthrough	clinvar
ANK2	HGNC:493	ENSG00000145362	Q01484	Ankyrin-2	clinvar
TNC	HGNC:5318	ENSG00000041982	P24821	Tenascin	clinvar
TBCEL-TECTA	HGNC:54857	ENSG00000285509		TBCEL-TECTA readthrough	clinvar
SHROOM2	HGNC:630	ENSG00000146950	Q13796	Protein Shroom2	clinvar
LRP4	HGNC:6696	ENSG00000134569	O75096	Low-density lipoprotein receptor-related protein 4	clinvar
MANBA	HGNC:6831	ENSG00000109323	O00462	Beta-mannosidase	clinvar
MPDZ	HGNC:7208	ENSG00000107186	O75970	Multiple PDZ domain protein	clinvar
MYBBP1A	HGNC:7546	ENSG00000132382	Q9BQG0	Myb-binding protein 1A	clinvar
MYH3	HGNC:7573	ENSG00000109063	P11055	Myosin-3	clinvar
MYH9	HGNC:7579	ENSG00000100345	P35579	Myosin-9	clinvar
MYO1C	HGNC:7597	ENSG00000197879	O00159	Unconventional myosin-Ic	clinvar
MYO1E	HGNC:7599	ENSG00000157483	Q12965	Unconventional myosin-Ie	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DTNA	Dystrobrevin alpha	May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.
SYNJ2	Synaptojanin-2	Inositol 5-phosphatase which may be involved in distinct membrane trafficking and signal transduction pathways.
TECTA	Alpha-tectorin	One of the major non-collagenous components of the tectorial membrane.
USH1C	Harmonin	Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells.
WFS1	Wolframin	Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store.
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.
CACNA1D	Voltage-dependent L-type calcium channel subunit alpha-1D	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
CAD	Multifunctional protein CAD	Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5…
PCDH15	Protocadherin-15	Calcium-dependent cell-adhesion protein.
KIF1B	Kinesin-like protein KIF1B	Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules.
TRIOBP	TRIO and F-actin-binding protein	Regulates actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin and prevents its depolymerization.
CPAP	Centrosomal P4.1-associated protein	Plays an important role in cell division and centrosome function by participating in centriole duplication.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
LRBA	Lipopolysaccharide-responsive and beige-like anchor protein	Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules.
CORIN	Atrial natriuretic peptide-converting enzyme	Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing.
GJD3	Gap junction delta-3 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
THADA	tRNA (32-2’-O)-methyltransferase regulator THADA	Together with methyltransferase FTSJ1, methylates the 2’-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs.
OTOP2	Proton channel OTOP2	Proton-selective ion channel open at neutral pH.
LYST	Lysosomal-trafficking regulator	Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes.
EPS8L2	Epidermal growth factor receptor kinase substrate 8-like protein 2	Stimulates guanine exchange activity of SOS1.
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL9A2	Collagen alpha-2(IX) chain	Structural component of hyaline cartilage and vitreous of the eye.
MYH14	Myosin-14	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
RABL6	Rab-like protein 6	Small GTPase involved in the regulation of cell growth and survival.
SPAG17	Sperm-associated antigen 17	Component of the central pair apparatus of ciliary axonemes.
CLEC16A	Protein CLEC16A	Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway.
TENM3	Teneurin-3	Involved in neural development by regulating the establishment of proper connectivity within the nervous system.
ARHGEF28	Rho guanine nucleotide exchange factor 28	Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors.
ACAN	Aggrecan core protein	This proteoglycan is a major component of extracellular matrix of cartilagenous tissues.
AGL	Glycogen debranching enzyme	Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation.
EPHA2	Ephrin type-A receptor 2	Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
FSCN2	Fascin-2	Acts as an actin bundling protein.
ANK2	Ankyrin-2	Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells.
TNC	Tenascin	Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration.
SHROOM2	Protein Shroom2	May be involved in endothelial cell morphology changes during cell spreading.
LRP4	Low-density lipoprotein receptor-related protein 4	Mediates SOST-dependent inhibition of bone formation.
MANBA	Beta-mannosidase	Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.
MPDZ	Multiple PDZ domain protein	Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses.
MYBBP1A	Myb-binding protein 1A	May activate or repress transcription via interactions with sequence specific DNA-binding proteins.
MYH3	Myosin-3	Muscle contraction.
MYH9	Myosin-9	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
MYO1C	Unconventional myosin-Ic	Myosins are actin-based motor molecules with ATPase activity.
MYO1E	Unconventional myosin-Ie	Actin-based motor molecule with ATPase activity.
MYO6	Unconventional myosin-VI	Myosins are actin-based motor molecules with ATPase activity.
MYO7A	Unconventional myosin-VIIa	Myosins are actin-based motor molecules with ATPase activity.
OTOG	Otogelin	Glycoprotein specific to acellular membranes of the inner ear.
PTPN13	Tyrosine-protein phosphatase non-receptor type 13	Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling.
RARA	Retinoic acid receptor alpha	Receptor for retinoic acid.

Protein-family classification

Druggable: 13 · Difficult: 18 · Unknown: 24 · Druggable fraction: 0.24

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	17	5.3×	8e-08
Nuclear receptor	1	7.0×	0.744
Complement	1	4.9×	0.744
Ion channel	1	2.0×	0.999
Phosphatase	1	1.5×	0.999
Antibody/Immunoglobulin	2	1.1×	0.999
Enzyme (other)	4	0.9×	0.999
Other/Unknown	24	0.8×	0.999
Protease	1	0.7×	0.999
Kinase	1	0.5×	0.999
GPCR	1	0.4×	0.999
Transcription factor	1	0.1×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TIMCC	Other/Unknown	no		DUF842_euk
DTNA	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1
SYNJ2	Other/Unknown	no		IPPc, RRM_dom, SAC_dom
TECTA	Other/Unknown	no		EGF, VWF_dom, ZP_dom
USH1C	Scaffold/PPI	no		PDZ, Harmonin_N, PDZ_sf
WFS1	Other/Unknown	no		TPR-like_helical_dom_sf, Wolframin, Wolframin_fam
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CACNA1D	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, LVDCC_a1dsu
CAD	Enzyme (other)	yes	2.1.3.2	Asp_carbamoyltransf, Dihydroorotase_CS, CarbamoylP_synth_ssu_N
PCDH15	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
KIF1B	Scaffold/PPI	no		FHA_dom, Kinesin_motor_dom, PH_domain
TRIOBP	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, M-RIP_PH
CPAP	Other/Unknown	no		CENPJ_C_dom, TCP10L/CENPJ, Tcp10_C_sf
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
LRBA	Scaffold/PPI	no		BEACH_dom, WD40_rpt, NBEA-like_DUF1088
CORIN	Protease	yes		SRCR, Trypsin_dom, LDrepeatLR_classA_rpt
GJD3	Other/Unknown	no		Connexin, Connexin_N, Connexin_CS
THADA	Other/Unknown	no		ARM-type_fold, THADA/TRM732_DUF2428, tRNA_methyltransferase_THADA
OTOP2	Other/Unknown	no		Otopetrin
LYST	Scaffold/PPI	no		BEACH_dom, WD40_rpt, PH-like_dom_sf
C10orf105	Other/Unknown	no		DUF5527
EPS8L2	Scaffold/PPI	no		SH3_domain, PTB/PI_dom, PH-like_dom_sf
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL9A2	Other/Unknown	no		Collagen, Collagen_superfamily
MYH14	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
RABL6	Other/Unknown	no		P-loop_NTPase, RABL6
SPAG17	Other/Unknown	no		SPAG17
OTOGL	Other/Unknown	no		VWF_dom, VWF_type-D, TIL_dom
CLEC16A	Other/Unknown	no		CLEC16A/TT9_N, CLEC16A/TT9, CLEC16A/TT9_C
TENM3	Scaffold/PPI	no		EGF, YD, CarboxyPept-like_regulatory
ARHGEF28	Scaffold/PPI	no		DH_dom, PH_domain, PKC_DAG/PE
ACAN	Complement	yes		Sushi_SCR_CCP_dom, Link_dom, EGF
AGL	Enzyme (other)	yes	3.2.1.33	Glycogen_debranch_met, 6-hairpin_glycosidase_sf, AGL/Gdb1
EPHA2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
FSCN2	Other/Unknown	no		Actin-crosslinking, Fascin, Fascin-like_dom
FPGT-TNNI3K	Other/Unknown	no
ANK2	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt
TNC	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
TBCEL-TECTA	Other/Unknown	no
SHROOM2	Scaffold/PPI	no		PDZ, ASD2_dom, ASD1_dom
LRP4	Other/Unknown	no		LDLR_classB_rpt, EGF, EGF-like_Ca-bd_dom
MANBA	Antibody/Immunoglobulin	yes		Glyco_hydro_2_cat, Galactose-bd-like_sf, Ig-like_fold
MPDZ	Scaffold/PPI	no		PDZ, L27_dom, L27_2
MYBBP1A	Enzyme (other)	yes	2.3.1.48	DNA_pol_V/MYBBP1A, ARM-like, ARM-type_fold
MYH3	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
MYH9	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
MYO1C	Other/Unknown	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_TH1
MYO1E	Scaffold/PPI	no		SH3_domain, Myosin_head_motor_dom-like, Myosin_TH1

Expression context

Cohort genes with no expression data: 0.

49 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	55
unknown	0

Top tissues across cohort

Tissue	Cohort genes
medial globus pallidus	5
ventricular zone	5
C1 segment of cervical spinal cord	4
stromal cell of endometrium	4
male germ line stem cell (sensu Vertebrata) in testis	4
primordial germ cell in gonad	4
calcaneal tendon	4
sural nerve	4
mucosa of transverse colon	3
adrenal tissue	3
right adrenal gland	3
right adrenal gland cortex	3
bronchial epithelial cell	3
monocyte	3
lower esophagus mucosa	3
tibia	3
corpus callosum	3
parotid gland	2
body of uterus	2
left ovary	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TIMCC	288	ubiquitous	marker	parotid gland, body of pancreas, gingival epithelium
DTNA	266	ubiquitous	marker	medial globus pallidus, globus pallidus, C1 segment of cervical spinal cord
SYNJ2	282	ubiquitous	marker	inferior vagus X ganglion, medial globus pallidus, C1 segment of cervical spinal cord
TECTA	166		marker	oocyte, secondary oocyte, parotid gland
USH1C	203	broad	marker	mucosa of transverse colon, C1 segment of cervical spinal cord, rectum
WFS1	280	ubiquitous	marker	right ovary, left ovary, body of uterus
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary
CACNA1D	219	broad	marker	buccal mucosa cell, adrenal tissue, right lung
CAD	223	ubiquitous	marker	body of uterus, stromal cell of endometrium, right lobe of liver
PCDH15	130	tissue_specific	marker	left adrenal gland cortex, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue
KIF1B	287	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, medial globus pallidus
TRIOBP	289	ubiquitous	marker	lower lobe of lung, cervix squamous epithelium, apex of heart
CPAP	246	ubiquitous	marker	sperm, left lobe of thyroid gland, right lobe of thyroid gland
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
LRBA	274	ubiquitous	marker	upper leg skin, bronchial epithelial cell, epithelium of bronchus
CORIN	176	tissue_specific	marker	cardiac muscle of right atrium, heart right ventricle, myocardium
GJD3	157	ubiquitous	yes	primordial germ cell in gonad, apex of heart, pancreatic ductal cell
THADA	276	ubiquitous	marker	calcaneal tendon, right uterine tube, right lobe of thyroid gland
OTOP2	37	tissue_specific	marker	mucosa of transverse colon, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
LYST	278	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
C10orf105	107	tissue_specific	yes	quadriceps femoris, blood, cerebellar vermis
EPS8L2	230	ubiquitous	marker	lower esophagus mucosa, metanephros cortex, esophagus mucosa
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
COL9A2	213	broad	marker	C1 segment of cervical spinal cord, tibia, adenohypophysis
MYH14	227	broad	marker	mucosa of transverse colon, ileal mucosa, gastrocnemius
FTO	294	ubiquitous	marker	cortical plate, bronchial epithelial cell, Brodmann (1909) area 10
RABL6	256	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SPAG17	173	broad	marker	right uterine tube, bronchial epithelial cell, sperm
OTOGL	152	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 28.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK2	6,423
MYH9	5,533
EPHA2	4,794
RARA	3,885
MYBBP1A	3,719
CAD	3,613
MPDZ	3,527
WFS1	3,409
MYO6	2,972
FTO	2,496

Intra-cohort edges

A	B	Sources
ACAN	COL9A2	string_interaction
ACAN	TNC	string_interaction
ADGRV1	CDH23	string_interaction
ADGRV1	OTOG	string_interaction
ADGRV1	OTOGL	string_interaction
ADGRV1	PCDH15	string_interaction
ARHGEF28	MYH9	intact
C10orf105	CDH23	string_interaction
CACNA1D	MYO6	string_interaction
CDH23	MYH14	string_interaction
CDH23	MYO6	string_interaction
CDH23	OTOG	string_interaction
CDH23	OTOGL	string_interaction
CDH23	PCDH15	string_interaction
CDH23	TRIOBP	string_interaction
CDH23	USH1C	biogrid_interaction, intact
COL4A4	MYH9	string_interaction
EPS8L2	KIF1B	intact
EPS8L2	WFS1	intact
MYH14	TECTA	string_interaction
MYH9	MYO1E	biogrid_interaction, intact
MYO1C	MYO1E	string_interaction
MYO6	OTOG	string_interaction
MYO6	TRIOBP	string_interaction
MYO7A	USH1C	biogrid_interaction
OTOG	OTOGL	string_interaction
OTOG	TECTA	string_interaction
OTOGL	TECTA	string_interaction

Structural data

PDB: 31 · AlphaFold-only: 22 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHA2	P29317	103
CAD	P27708	55
FTO	Q9C0B1	28
TNC	P24821	21
RARA	P10276	14
PTPN13	Q12923	12
USH1C	Q9Y6N9	11
ANK2	Q01484	11
MPDZ	O75970	9
PCDH15	Q96QU1	8
MYH9	P35579	8
MYO6	Q9UM54	8
CDH23	Q9H251	6
CACNA1D	Q01668	6
CPAP	Q9HC77	6
COL9A2	Q14055	4
ACAN	P16112	4
THADA	Q6YHU6	2
EPS8L2	Q9H6S3	2
COL4A4	P53420	2
MYH14	Q7Z406	2
ARHGEF28	Q8N1W1	2
SHROOM2	Q13796	2
DTNA	Q9Y4J8	1
SYNJ2	O15056	1
KIF1B	O60333	1
LRBA	P50851	1
AGL	P35573	1
LRP4	O75096	1
MYO1C	O00159	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MANBA	O00462	96.05
TIMCC	Q96C01	95.42
FSCN2	O14926	93.79
MYO1E	Q12965	80.46
OTOP2	Q7RTS6	78.55
GJD3	Q8N144	78.25
TENM3	Q9P273	77.76
TECTA	O75443	77.64
MYBBP1A	Q9BQG0	74.69
MYH3	P11055	74.35
WFS1	O76024	73.85
OTOGL	Q3ZCN5	72.19
CLEC16A	Q2KHT3	72.17
CORIN	Q9Y5Q5	70.20
SPAG17	Q6Q759	64.20
C10orf105	Q8TEF2	63.46
RABL6	Q3YEC7	60.84
COL11A1	P12107	53.06
TRIOBP	Q9H2D6	40.77
ADGRV1	Q8WXG9
LYST	Q99698
OTOG	Q6ZRI0

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 154. Enrichment computed across 55 evidence-associated genes (41 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 41 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sensory processing of sound by outer hair cells of the cochlea	11	54.7×	6e-15	USH1C, CDH23, PCDH15, TRIOBP, EPS8L2, OTOGL, FSCN2, MYH9 (+3 more)
Sensory processing of sound by inner hair cells of the cochlea	10	39.8×	3e-12	USH1C, CDH23, CACNA1D, PCDH15, TRIOBP, EPS8L2, FSCN2, MYH9 (+2 more)
Sensory processing of sound	5	37.6×	1e-05	CDH23, CACNA1D, MYH9, MYO1C, MYO7A
ECM proteoglycans	5	18.3×	3e-04	COL4A4, COL9A2, ACAN, TNC, LRP4
Sensory Perception	5	11.6×	0.002	CDH23, CACNA1D, MYH9, MYO1C, MYO7A
EPH-Ephrin signaling	4	16.1×	0.003	MYH14, ARHGEF28, EPHA2, MYH9
EPHA-mediated growth cone collapse	3	27.9×	0.004	MYH14, EPHA2, MYH9
Nervous system development	6	6.3×	0.007	CACNA1D, ADGRV1, MYH14, ARHGEF28, ANK2, MYH9
Collagen chain trimerization	3	19.0×	0.009	COL11A1, COL4A4, COL9A2
NCAM1 interactions	3	18.2×	0.009	CACNA1D, COL4A4, COL9A2
Membrane Trafficking	6	5.4×	0.010	SYNJ2, KIF1B, ANK2, MYH9, MYO1C, MYO6
Assembly of collagen fibrils and other multimeric structures	3	14.7×	0.013	COL11A1, COL4A4, COL9A2
Vesicle-mediated transport	6	5.1×	0.013	SYNJ2, KIF1B, ANK2, MYH9, MYO1C, MYO6
Sema4D in semaphorin signaling	2	32.8×	0.017	MYH14, MYH9
RHO GTPases activate CIT	2	29.3×	0.017	MYH14, MYH9
RHO GTPases Activate ROCKs	2	29.3×	0.017	MYH14, MYH9
Collagen degradation	3	12.9×	0.017	COL11A1, COL4A4, COL9A2
Collagen biosynthesis and modifying enzymes	3	12.5×	0.017	COL11A1, COL4A4, COL9A2
Axon guidance	5	5.5×	0.017	CACNA1D, MYH14, ARHGEF28, ANK2, MYH9
Sema4D induced cell migration and growth-cone collapse	2	27.9×	0.017	MYH14, MYH9
Non-integrin membrane-ECM interactions	3	11.3×	0.017	COL11A1, COL4A4, TNC
RHO GTPases activate PAKs	2	26.5×	0.018	MYH14, MYH9
Integrin cell surface interactions	3	9.8×	0.023	COL4A4, COL9A2, TNC
Semaphorin interactions	2	19.2×	0.031	MYH14, MYH9
Parasite infection	2	16.9×	0.037	MYH9, MYO1C
Leishmania phagocytosis	2	16.9×	0.037	MYH9, MYO1C
RHO GTPases activate PKNs	2	15.5×	0.042	MYH14, MYH9
Fcgamma receptor (FCGR) dependent phagocytosis	2	13.6×	0.050	MYH9, MYO1C
RHOU GTPase cycle	2	13.6×	0.050	EPHA2, MYO6
Pyrimidine biosynthesis	1	92.8×	0.050	CAD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 50 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sensory perception of sound	13	26.2×	7e-13	TECTA, USH1C, WFS1, CDH23, CACNA1D, PCDH15, TRIOBP, ADGRV1 (+5 more)
sensory perception of light stimulus	5	187.2×	4e-09	USH1C, CDH23, PCDH15, ADGRV1, MYO7A
actin filament-based movement	6	96.3×	4e-09	MYH14, MYH3, MYH9, MYO1C, MYO6, MYO7A
equilibrioception	4	192.6×	3e-07	USH1C, CDH23, PCDH15, MYO7A
auditory receptor cell stereocilium organization	4	67.4×	3e-05	TECTA, CDH23, TRIOBP, MYO7A
L-arabinose metabolic process	2	337.0×	7e-04	OTOGL, OTOG
photoreceptor cell maintenance	4	28.7×	7e-04	USH1C, CDH23, PCDH15, ADGRV1
endocytosis	6	11.4×	8e-04	ANK2, LRP4, MYO1C, MYO1E, MYO6, MYO7A
inner ear receptor cell stereocilium organization	3	50.6×	0.001	USH1C, ADGRV1, OTOGL
visual perception	6	9.5×	0.002	WFS1, CDH23, ADGRV1, COL11A1, FSCN2, MYO7A
actin filament organization	5	11.9×	0.003	SHROOM2, MYO1C, MYO1E, MYO6, MYO7A
membrane depolarization during SA node cell action potential	2	134.8×	0.003	CACNA1D, ANK2
positive regulation of calcium ion transport	3	34.9×	0.003	WFS1, CACNA1D, ANK2
intracellular protein localization	5	10.5×	0.004	LRBA, OTOGL, ANK2, MYO6, MYO7A
glomerular basement membrane development	2	61.3×	0.015	COL4A4, MYO1E
inner ear morphogenesis	3	18.1×	0.018	USH1C, COL11A1, MYO6
inner ear auditory receptor cell differentiation	2	48.1×	0.020	USH1C, MYO6
nervous system process	2	48.1×	0.020	WFS1, ADGRV1
positive regulation of transcription by RNA polymerase III	2	37.5×	0.030	MYBBP1A, MYO1C
detection of mechanical stimulus involved in sensory perception of sound	2	37.5×	0.030	ADGRV1, COL11A1
eye photoreceptor cell development	2	33.7×	0.035	FSCN2, MYO7A
female pregnancy	3	12.6×	0.037	CAD, CORIN, RARA
eye pigment granule organization	1	337.0×	0.039	SHROOM2
astral microtubule nucleation	1	337.0×	0.039	CPAP
protein localization to T-tubule	1	337.0×	0.039	ANK2
pigment granule transport	1	337.0×	0.039	MYO7A
vibrational conductance of sound to the inner ear	1	337.0×	0.039	OTOGL
Sertoli cell fate commitment	1	337.0×	0.039	RARA
notochord cell development	1	337.0×	0.039	EPHA2
regulation of white fat cell proliferation	1	337.0×	0.039	FTO

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dexamethasone	Phase 3 (in late-stage trials)
Ebselen	Phase 3 (in late-stage trials)
Famciclovir	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anakinra, Gentamicin, Latanoprost.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 47

Druggability breadth: 21 of 55 evidence-associated genes (38%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SYNJ2	PYRVINIUM
CACNA1D	BEPRIDIL
MYH14	TUCATINIB
FTO	FLUORESCEIN
AGL	MIGLUSTAT
EPHA2	PONATINIB
RARA	BEXAROTENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHA2	50	4
CACNA1D	48	4
FTO	18	4
RARA	11	4
AGL	4	4
SYNJ2	3	4
MYH14	1	4
MYH9	1	2
TIMCC	0	0
DTNA	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRVINIUM	4	SYNJ2
CHLORHEXIDINE	4	SYNJ2
BEPRIDIL	4	CACNA1D
IMIPRAMINE	4	CACNA1D
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D
SAQUINAVIR	4	CACNA1D
DULOXETINE	4	CACNA1D
DIAZEPAM	4	CACNA1D
SERTINDOLE	4	CACNA1D
QUINIDINE	4	CACNA1D
LAMIVUDINE	4	CACNA1D
PIMOZIDE	4	CACNA1D
PHENYTOIN	4	CACNA1D
TERFENADINE	4	CACNA1D
CISAPRIDE	4	CACNA1D
SOLIFENACIN	4	CACNA1D
NIFEDIPINE	4	CACNA1D
DILTIAZEM	4	CACNA1D
NILOTINIB	4	CACNA1D, EPHA2
ASTEMIZOLE	4	CACNA1D
TERODILINE	4	CACNA1D
CLOZAPINE	4	CACNA1D
MIBEFRADIL	4	CACNA1D
DOFETILIDE	4	CACNA1D
THIORIDAZINE	4	CACNA1D
PAROXETINE	4	CACNA1D
DONEPEZIL	4	CACNA1D
IBUTILIDE	4	CACNA1D
SUNITINIB	4	CACNA1D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EPHA2	567	Binding:565, Functional:1, ADMET:1
RARA	368	Binding:279, Functional:85, ADMET:4
CACNA1D	233	Binding:145, Functional:81, Toxicity:5, ADMET:2
FTO	153	Binding:153
PTPN13	23	Binding:22, ADMET:1
CAD	17	Binding:16, ADMET:1
MANBA	13	Binding:11, Functional:2
MYH9	10	Binding:10
PCDH15	9	Binding:9
SYNJ2	7	Binding:7
AGL	4	Binding:4
TIMCC	1	Binding:1
WFS1	1	Binding:1
KIF1B	1	Binding:1
LRBA	1	Binding:1
MYH14	1	Binding:1
RABL6	1	Binding:1
MYBBP1A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAD	2.1.3.2, 3.5.2.3, 6.3.5.5	aspartate carbamoyltransferase, dihydroorotase, carbamoyl-phosphate synthase (glutamine-hydrolysing)
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
AGL	3.2.1.33	amylo-alpha-1,6-glucosidase
EPHA2	2.7.10.1	receptor protein-tyrosine kinase
MYBBP1A	2.3.1.48	histone acetyltransferase
PTPN13	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CACNA1D	233
FTO	153
EPHA2	567
RARA	368

Pharmacogenomics

Cohort genes with a PharmGKB record: 53; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PYRVINIUM	4	SYNJ2
CHLORHEXIDINE	4	SYNJ2
BEPRIDIL	4	CACNA1D
IMIPRAMINE	4	CACNA1D
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D
SAQUINAVIR	4	CACNA1D
DULOXETINE	4	CACNA1D
DIAZEPAM	4	CACNA1D
SERTINDOLE	4	CACNA1D
QUINIDINE	4	CACNA1D
LAMIVUDINE	4	CACNA1D
PIMOZIDE	4	CACNA1D
PHENYTOIN	4	CACNA1D
TERFENADINE	4	CACNA1D
CISAPRIDE	4	CACNA1D
SOLIFENACIN	4	CACNA1D
NIFEDIPINE	4	CACNA1D
DILTIAZEM	4	CACNA1D
NILOTINIB	4	CACNA1D, EPHA2
ASTEMIZOLE	4	CACNA1D
TERODILINE	4	CACNA1D
CLOZAPINE	4	CACNA1D
MIBEFRADIL	4	CACNA1D
DOFETILIDE	4	CACNA1D
THIORIDAZINE	4	CACNA1D
PAROXETINE	4	CACNA1D
DONEPEZIL	4	CACNA1D
IBUTILIDE	4	CACNA1D
SUNITINIB	4	CACNA1D

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	SYNJ2, CACNA1D, MYH14, FTO, AGL, EPHA2, RARA
B	Phased (≥1) drug, not yet approved	1	MYH9
C	Druggable family + PDB, no drug	4	CAD, ACAN, TNC, PTPN13
D	Druggable family + AlphaFold only, no drug	4	ADGRV1, CORIN, MANBA, MYBBP1A
E	Difficult family or no structure, no drug	39	TIMCC, DTNA, TECTA, USH1C, WFS1, CDH23, PCDH15, KIF1B, TRIOBP, CPAP (+29 more)

Undrugged target profiles

47 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COL4A4	0	MYH9
TIMCC	1	—
DTNA	0	—
TECTA	0	—
USH1C	0	—
WFS1	1	—
CDH23	0	—
CAD	17	—
PCDH15	9	—
KIF1B	1	—
TRIOBP	0	—
CPAP	0	—
ADGRV1	0	—
LRBA	1	—
CORIN	0	—
GJD3	0	—
THADA	0	—
OTOP2	0	—
LYST	0	—
C10orf105	0	—
EPS8L2	0	—
COL11A1	0	—
COL9A2	0	—
RABL6	1	—
SPAG17	0	—
OTOGL	0	—
CLEC16A	0	—
TENM3	0	—
ARHGEF28	0	—
ACAN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 31.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	19
PHASE4	3
PHASE3	3
PHASE2	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
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)
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease
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
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
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MONTELUKAST	4	3
VENLAFAXINE	4	3
GADOPENTETATE DIMEGLUMINE	4	1
HYALURONIC ACID	4	1
LAMOTRIGINE	4	1
PHENOL	4	1
TETRACAINE	4	1
EBSELEN	3	1
GADOTERIC ACID	2	1
CHEMBL5205127	0	1
CHEMBL5268979	0	1
CYCLIC ADENOSINE MONOPHOSPHATE	0	1