Autosomal recessive nonsyndromic hearing loss 4

Summary

Autosomal recessive nonsyndromic hearing loss 4 (MONDO:0010933) is a disease caused by SLC26A4 (GenCC Definitive), with 5 cohort genes and 2 clinical trials.

At a glance

• Causal gene: SLC26A4 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 857
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 4
Mondo ID	MONDO:0010933
MeSH	C566366
OMIM	600791
DOID	DOID:0110498
UMLS	C3538946
MedGen	761234
GARD	0022584
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 4 with enlarged vestibular aqueduct · autosomal recessive nonsyndromic deafness 4 · autosomal recessive nonsyndromic deafness type 4 · deafness, autosomal recessive 4, with enlarged vestibular aqueduct · DFNB4 · enlarged vestibular aqueduct · enlarged vestibular aqueduct, digenic · neurosensory nonsyndromic recessive deafness 4

Data availability: 857 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 4

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

182 uncertain significance, 125 likely pathogenic, 103 pathogenic, 83 conflicting classifications of pathogenicity, 76 pathogenic/likely pathogenic, 13 benign, 9 likely benign, 9 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
424816	NM_000441.1(SLC26A4):c.[349C>T];[578C>T]		Pathogenic	no assertion criteria provided
3775116	NM_012188.5(FOXI1):c.748dup (p.Asp250fs)	FOXI1	Pathogenic	criteria provided, single submitter
1033030	NM_000441.2(SLC26A4):c.2184_2187dup (p.Gln730fs)	LOC123956210	Pathogenic	criteria provided, single submitter
188869	NM_000441.2(SLC26A4):c.2127del (p.Phe709fs)	LOC123956210	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1929401	NM_000441.2(SLC26A4):c.2113C>T (p.Gln705Ter)	LOC123956210	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601760	NM_000441.2(SLC26A4):c.2116T>C (p.Cys706Arg)	LOC123956210	Pathogenic	criteria provided, single submitter
3601761	NM_000441.2(SLC26A4):c.2128G>T (p.Asp710Tyr)	LOC123956210	Pathogenic	criteria provided, single submitter
1033029	NM_000441.2(SLC26A4):c.1615-2A>G	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065203	NM_000441.2(SLC26A4):c.1786C>T (p.Gln596Ter)	SLC26A4	Pathogenic	criteria provided, single submitter
1065204	NM_000441.2(SLC26A4):c.317C>A (p.Ala106Asp)	SLC26A4	Pathogenic	criteria provided, multiple submitters, no conflicts
1065207	NM_000441.2(SLC26A4):c.387del (p.Phe130fs)	SLC26A4	Pathogenic	criteria provided, multiple submitters, no conflicts
1065210	NM_000441.2(SLC26A4):c.754T>C (p.Ser252Pro)	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065211	NM_000441.2(SLC26A4):c.415+2T>C	SLC26A4	Pathogenic	criteria provided, single submitter
1065212	NM_000441.2(SLC26A4):c.1991C>T (p.Ala664Val)	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065213	NM_000441.2(SLC26A4):c.1299dup (p.Ala434fs)	SLC26A4	Pathogenic	no assertion criteria provided
1068420	NM_000441.2(SLC26A4):c.1803+2T>C	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069712	NM_000441.2(SLC26A4):c.1614+1G>T	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070843	NM_000441.2(SLC26A4):c.1984dup (p.Cys662fs)	SLC26A4	Pathogenic	criteria provided, multiple submitters, no conflicts
1073256	NM_000441.2(SLC26A4):c.25G>T (p.Glu9Ter)	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073278	NM_000441.2(SLC26A4):c.1150-1G>T	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073634	NM_000441.2(SLC26A4):c.1343C>A (p.Ser448Ter)	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074192	NM_000441.2(SLC26A4):c.2026del (p.Leu676fs)	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075541	NM_000441.2(SLC26A4):c.170C>A (p.Ser57Ter)	SLC26A4	Pathogenic	criteria provided, multiple submitters, no conflicts
1075641	NM_000441.2(SLC26A4):c.1150-1G>A	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1185073	NM_000441.2(SLC26A4):c.593_600+8del	SLC26A4	Pathogenic	no assertion criteria provided
1185667	NM_000441.2(SLC26A4):c.3G>A (p.Met1Ile)	SLC26A4	Pathogenic	no assertion criteria provided
1185668	NM_000441.2(SLC26A4):c.79T>C (p.Tyr27His)	SLC26A4	Pathogenic	no assertion criteria provided
1185669	NM_000441.2(SLC26A4):c.305-1G>A	SLC26A4	Pathogenic	no assertion criteria provided
1185671	NM_000441.2(SLC26A4):c.600+2T>C	SLC26A4	Pathogenic	no assertion criteria provided
1185672	NM_000441.2(SLC26A4):c.667_669dup (p.Phe223dup)	SLC26A4	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 12 · 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
SLC26A4	Definitive	Autosomal recessive	autosomal recessive nonsyndromic hearing loss 4	10
FOXI1	Limited	Autosomal recessive	autosomal recessive nonsyndromic hearing loss 4	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXI1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
FOXI1	Orphanet:705	Pendred syndrome
SLC26A4	Orphanet:705	Pendred syndrome
SLC26A4	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
SLC26A4	Orphanet:95713	Athyreosis
SLC26A4	Orphanet:95720	Thyroid hypoplasia
TJP2	Orphanet:238475	Familial hypercholanemia
TJP2	Orphanet:480483	Progressive familial intrahepatic cholestasis type 4
TJP2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
KCNJ10	Orphanet:199343	EAST syndrome
KCNJ10	Orphanet:705	Pendred syndrome
KCNJ10	Orphanet:98809	Paroxysmal kinesigenic dyskinesia

Cohort genes → proteins

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FOXI1	HGNC:3815	ENSG00000168269	Q12951	Forkhead box protein I1	gencc,clinvar
SLC26A4	HGNC:8818	ENSG00000091137	O43511	Pendrin	gencc,clinvar
TJP2	HGNC:11828	ENSG00000119139	Q9UDY2	Tight junction protein 2	clinvar
SLC26A4-AS1	HGNC:22385	ENSG00000233705		SLC26A4 antisense RNA 1	clinvar
KCNJ10	HGNC:6256	ENSG00000177807	P78508	ATP-sensitive inward rectifier potassium channel 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXI1	Forkhead box protein I1	Transcriptional activator required for the development of normal hearing, sense of balance and kidney function.
SLC26A4	Pendrin	Sodium-independent transporter of chloride and iodide.
TJP2	Tight junction protein 2	Plays a role in tight junctions and adherens junctions.
KCNJ10	ATP-sensitive inward rectifier potassium channel 10	May be responsible for potassium buffering action of glial cells in the brain.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.4

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
Ion channel	1	22.3×	0.157
Transporter	1	15.6×	0.157
Scaffold/PPI	1	3.5×	0.429
Transcription factor	1	1.6×	0.595
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FOXI1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
SLC26A4	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom
TJP2	Scaffold/PPI	no		SH3_domain, PDZ, ZO
SLC26A4-AS1	Other/Unknown	no
KCNJ10	Ion channel	yes		K_chnl_inward-rec_Kir1.2, K_chnl_inward-rec_Kir_cyto, Ig_E-set

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of thyroid gland	2
thyroid gland	2
adult mammalian kidney	1
metanephros cortex	1
olfactory segment of nasal mucosa	1
palpebral conjunctiva	1
corpus callosum	1
descending thoracic aorta	1
thoracic aorta	1
left lobe of thyroid gland	1
C1 segment of cervical spinal cord	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXI1	46	tissue_specific	marker	metanephros cortex, adult mammalian kidney, olfactory segment of nasal mucosa
SLC26A4	190	tissue_specific	marker	palpebral conjunctiva, right lobe of thyroid gland, thyroid gland
TJP2	134	ubiquitous	marker	corpus callosum, descending thoracic aorta, thoracic aorta
SLC26A4-AS1	164	tissue_specific	marker	right lobe of thyroid gland, thyroid gland, left lobe of thyroid gland
KCNJ10	185	tissue_specific	marker	C1 segment of cervical spinal cord, medial globus pallidus, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TJP2	2,916
KCNJ10	1,862
SLC26A4	1,648
FOXI1	1,523
SLC26A4-AS1	0

Intra-cohort edges

A	B	Sources
FOXI1	KCNJ10	string_interaction
FOXI1	SLC26A4	string_interaction
KCNJ10	SLC26A4	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNJ10	P78508	4
TJP2	Q9UDY2	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC26A4	O43511	82.72
FOXI1	Q12951	60.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC26A4 causes Pendred syndrome (PDS)	1	3806.7×	0.007	SLC26A4
Potassium transport channels	1	1268.9×	0.010	KCNJ10
Inorganic anion exchange by SLC26 transporters	1	423.0×	0.014	SLC26A4
G protein gated Potassium channels	1	380.7×	0.014	KCNJ10
Apoptotic cleavage of cell adhesion proteins	1	346.1×	0.014	TJP2
Inwardly rectifying K+ channels	1	237.9×	0.015	KCNJ10
Activation of GABAB receptors	1	200.3×	0.015	KCNJ10
Signaling by Hippo	1	181.3×	0.015	TJP2
GABA B receptor activation	1	181.3×	0.015	KCNJ10
Activation of G protein gated Potassium channels	1	131.3×	0.017	KCNJ10
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	131.3×	0.017	KCNJ10
GABA receptor activation	1	105.7×	0.020	KCNJ10
SLC transporter disorders	1	68.0×	0.028	SLC26A4
RHOB GTPase cycle	1	51.4×	0.032	TJP2
RHOC GTPase cycle	1	48.8×	0.032	TJP2
Disorders of transmembrane transporters	1	46.4×	0.032	SLC26A4
Potassium Channels	1	44.8×	0.032	KCNJ10
R-HSA-425393	1	43.3×	0.032	SLC26A4
Neurotransmitter receptors and postsynaptic signal transmission	1	33.4×	0.039	KCNJ10
Transmission across Chemical Synapses	1	25.4×	0.047	KCNJ10
RHOA GTPase cycle	1	24.9×	0.047	TJP2
SLC-mediated transmembrane transport	1	19.7×	0.057	SLC26A4
Neuronal System	1	14.8×	0.072	KCNJ10
Transport of small molecules	1	8.4×	0.119	SLC26A4
Disease	1	4.4×	0.212	SLC26A4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glutamate reuptake	1	2106.5×	0.010	KCNJ10
inorganic anion transport	1	1404.3×	0.010	SLC26A4
positive regulation of blood-brain barrier permeability	1	842.6×	0.010	TJP2
iodide transport	1	601.9×	0.010	SLC26A4
regulation of membrane permeability	1	601.9×	0.010	TJP2
protein localization to cell-cell junction	1	468.1×	0.010	TJP2
homotypic cell-cell adhesion	1	421.3×	0.010	TJP2
regulation of pH	1	351.1×	0.010	SLC26A4
establishment of endothelial intestinal barrier	1	351.1×	0.010	TJP2
regulation of resting membrane potential	1	324.1×	0.010	KCNJ10
intestinal absorption	1	300.9×	0.010	TJP2
sulfate transmembrane transport	1	300.9×	0.010	SLC26A4
cellular response to potassium ion	1	263.3×	0.010	KCNJ10
central nervous system myelination	1	247.8×	0.010	KCNJ10
regulation of long-term neuronal synaptic plasticity	1	247.8×	0.010	KCNJ10
potassium ion homeostasis	1	191.5×	0.011	KCNJ10
embryo development ending in birth or egg hatching	1	183.2×	0.011	FOXI1
regulation of monoatomic ion transmembrane transport	1	183.2×	0.011	KCNJ10
cell-cell junction organization	1	156.0×	0.012	TJP2
adult walking behavior	1	123.9×	0.014	KCNJ10
maintenance of blood-brain barrier	1	120.4×	0.014	TJP2
potassium ion import across plasma membrane	1	91.6×	0.018	KCNJ10
inner ear morphogenesis	1	75.2×	0.021	FOXI1
non-motile cilium assembly	1	72.6×	0.021	KCNJ10
chloride transmembrane transport	1	59.3×	0.024	SLC26A4
regulation of protein localization	1	51.4×	0.027	SLC26A4
potassium ion transport	1	47.9×	0.028	KCNJ10
monoatomic ion transport	1	39.0×	0.033	SLC26A4
anatomical structure morphogenesis	1	34.8×	0.035	FOXI1
potassium ion transmembrane transport	1	34.0×	0.035	KCNJ10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FOXI1	0	0
SLC26A4	0	0
TJP2	0	0
SLC26A4-AS1	0	0
KCNJ10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC26A4	37	Binding:37
KCNJ10	10	Binding:10

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	KCNJ10
D	Druggable family + AlphaFold only, no drug	1	SLC26A4
E	Difficult family or no structure, no drug	3	FOXI1, TJP2, SLC26A4-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FOXI1	0	—
SLC26A4	37	—
TJP2	0	—
SLC26A4-AS1	0	—
KCNJ10	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02798783	Not specified	COMPLETED	Enlarged Vestibular Aqueduct Registry
NCT04934605	Not specified	UNKNOWN	Genotype-phenotype Correlation of SLC26A4 in CI Patients With EVA