ILDR1

Summary

ILDR1 (immunoglobulin like domain containing receptor 1, HGNC:28741) is a protein-coding gene on chromosome 3q13.33, encoding Immunoglobulin-like domain-containing receptor 1 (Q86SU0). Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (tTJs).

This gene encodes a protein that contains an immunoglobulin-like domain. The encoded protein may function as a multimeric receptor at the cell surface. The expression of this gene may be a diagnostic marker for cancer progression. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene.

Source: NCBI Gene 286676 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 339 total — 19 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001199799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28741
Approved symbol	ILDR1
Name	immunoglobulin like domain containing receptor 1
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC50831
Ensembl gene	ENSG00000145103
Ensembl biotype	protein_coding
OMIM	609739
Entrez	286676

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000273691, ENST00000344209, ENST00000393631, ENST00000460554, ENST00000642615, ENST00000891213, ENST00000891214, ENST00000891215, ENST00000891216, ENST00000914512, ENST00000969537

RefSeq mRNA: 3 — MANE Select: NM_001199799 NM_001199799, NM_001199800, NM_175924

CCDS: CCDS3008, CCDS56270, CCDS56271

Canonical transcript exons

ENST00000344209 — 8 exons

Exon	Start	End
ENSE00001235573	121993150	121993970
ENSE00001298769	121987323	121988408
ENSE00001859618	122022020	122022247
ENSE00003503737	121994182	121994313
ENSE00003571672	122001308	122001454
ENSE00003617046	122001745	122001864
ENSE00003625543	122006991	122007161
ENSE00003642085	122005244	122005393

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 86.95.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4574 / max 28.5729, expressed in 197 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44116	0.4574	197

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	86.95	gold quality
kidney epithelium	UBERON:0004819	85.65	silver quality
nasal cavity epithelium	UBERON:0005384	83.16	gold quality
ileal mucosa	UBERON:0000331	82.77	silver quality
bronchial epithelial cell	CL:0002328	81.64	gold quality
palpebral conjunctiva	UBERON:0001812	80.84	gold quality
bronchus	UBERON:0002185	80.25	gold quality
caput epididymis	UBERON:0004358	79.94	gold quality
mucosa of transverse colon	UBERON:0004991	79.75	gold quality
epithelial cell of pancreas	CL:0000083	79.73	silver quality
parotid gland	UBERON:0001831	78.30	gold quality
seminal vesicle	UBERON:0000998	78.20	gold quality
rectum	UBERON:0001052	77.34	gold quality
pancreatic ductal cell	CL:0002079	77.14	silver quality
epithelium of nasopharynx	UBERON:0001951	76.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.17	gold quality
islet of Langerhans	UBERON:0000006	74.82	gold quality
colonic mucosa	UBERON:0000317	74.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.28	silver quality
adult mammalian kidney	UBERON:0000082	73.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	73.79	gold quality
nasal cavity mucosa	UBERON:0001826	73.30	gold quality
pancreas	UBERON:0001264	73.20	gold quality
cauda epididymis	UBERON:0004360	73.11	gold quality
body of pancreas	UBERON:0001150	72.84	gold quality
endometrium	UBERON:0001295	71.60	gold quality
metanephros cortex	UBERON:0010533	71.48	gold quality
esophagus squamous epithelium	UBERON:0006920	71.41	gold quality
kidney	UBERON:0002113	71.31	gold quality
saliva-secreting gland	UBERON:0001044	71.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting ILDR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-1207-3P	98.99	66.22	1532

Literature-anchored findings (GeneRIF, showing 11)

• Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42. (PMID:21255762)
• The analysis of gene expression was extended to Refractory Anemia (RA) and Refractory Anemia with excess blasts (RAEB) cases revealing ILDR1 overexpression in 36% of RAEB subgroup. (PMID:22365942)
• The findings show the heterogeneity of the molecular organization of tTJs in terms of the content of LSR, ILDR1 or ILDR2, and suggest that ILDR1-mediated recruitment of tricellulin to TCs is required for hearing. (PMID:23239027)
• Data indicate a mutation in immunoglobulin-like domain containing receptor 1 (ILDR1) as a causative gene for autosomal-recessive non-syndromic hearing loss (arNSHL) in a consanguineous Saudi family with three affected children. (PMID:24768815)
• Whole-exome sequencing of a Korean multiplex family segregating partial deafness identified a novel homozygous ILDR1 variant (p.P69H) within the Ig-like domain. (PMID:25668204)
• consanguineous deaf families with novelmutations in the ILDR1 gene, were identified. (PMID:26440088)
• We discovered two genome-wide significant SNPs. The first was novel and near ISG20. The second was in TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. Motivated by our TRIOBP results, we also looked at exons in known hearing loss genes, and identified two additional SNPs, rs2877561 in ILDR1 and rs9493672 in EYA4 (at a significance threshold adjusted for number of SNPs in those regions). (PMID:27764096)
• The present study reports a first ILDR1 gene mutation in a consanguineous family with hearing loss in the UAE, and confirms that the whole-exome sequencing approach is a robust tool for the diagnosis of monogenic diseases with high levels of allelic and locus heterogeneity. (PMID:28945813)
• this is the first ILDR1 and MYO6 mutations recognized in the southwest Iran. Our data expands the spectrum of mutations in ILDR1 and MYO6 genes. (PMID:29224747)
• The study shows that the novel p.G141R mutation in ILDR1 is the likely genetic cause for the hearing impairment in two unrelated Chinese Han DFNB42 families. (PMID:29849566)
• Imputation of SNPs associated with presbycusis through linkage disequilibrium analysis in the ILDR1 gene. (PMID:36814109)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ildr1b	ENSDARG00000040910
danio_rerio	ildr1a	ENSDARG00000103929
mus_musculus	Ildr1	ENSMUSG00000022900
rattus_norvegicus	Ildr1	ENSRNOG00000002289

Paralogs (2): LSR (ENSG00000105699), ILDR2 (ENSG00000143195)

Protein

Protein identifiers

Immunoglobulin-like domain-containing receptor 1 — Q86SU0 (reviewed: Q86SU0)

Alternative names: Angulin-2

All UniProt accessions (1): Q86SU0

UniProt curated annotations — full annotation on UniProt →

Function. Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (tTJs). Crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs. Mediates fatty acids and lipoproteins-stimulated CCK/cholecystokinin secretion in the small intestine. In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1. (Microbial infection) Promotes influenza virus infection by inhibiting viral nucleoprotein NP binding to PLSCR1 and thereby PLSCR1-mediated antiviral activity.

Subunit / interactions. Homooligomer. Interacts with MARVELD2 and OCLN; the interaction is required to recruit MARVELD2 to tricellular contacts. Interacts (via C-terminus) with TRA2A, TRA2B and SRSF1. Interacts with PLSCR1.

Subcellular location. Cell membrane. Cell junction. Tight junction. Cytoplasm Cytoplasm. Cytosol.

Tissue specificity. Mainly expressed in prostate and to a lower extent in testis, pancreas, kidney, heart and liver.

Disease relevance. Deafness, autosomal recessive, 42 (DFNB42) [MIM:609646] A prelingual, non-progressive 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.

Similarity. Belongs to the immunoglobulin superfamily. LISCH7 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86SU0-1	1, Alpha	yes
Q86SU0-2	2
Q86SU0-3	3
Q86SU0-4	4
Q86SU0-5	5, Beta
Q86SU0-6	6, Alpha'

RefSeq proteins (3): NP_001186728, NP_001186729, NP_787120 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR008664	LISCH7	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051874	Ig-like_domain-LISCH7	Family

Pfam: PF05624

UniProt features (28 total): splice variant 9, sequence variant 6, compositionally biased region 3, modified residue 2, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SU0-F1	58.87	0.22

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 (2): 499, 501

Disulfide bonds (1): 45–145

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, CHANDRAN_METASTASIS_DN, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RNA_SPLICING, GOBP_SECRETION, GOBP_POSITIVE_REGULATION_OF_HORMONE_SECRETION, GOBP_SIGNAL_RELEASE, GOBP_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_FATTY_ACID

GO Biological Process (10): epithelial structure maintenance (GO:0010669), peptide hormone secretion (GO:0030072), regulation of RNA splicing (GO:0043484), establishment of localization in cell (GO:0051649), protein localization to tricellular tight junction (GO:0061833), response to fatty acid (GO:0070542), positive regulation of peptide hormone secretion (GO:0090277), tricellular tight junction assembly (GO:1904274), cellular response to leukemia inhibitory factor (GO:1990830), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): identical protein binding (GO:0042802), high-density lipoprotein particle receptor activity (GO:0070506), protein binding (GO:0005515)

GO Cellular Component (9): cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), protein-containing complex (GO:0032991), tricellular tight junction (GO:0061689), tight junction (GO:0070160), cytoplasm (GO:0005737), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
tight junction	2
tissue homeostasis	1
peptide secretion	1
hormone secretion	1
nitrogen compound transport	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
establishment of localization	1
cellular localization	1
protein localization to cell-cell junction	1
response to lipid	1
response to oxygen-containing compound	1
positive regulation of peptide secretion	1
peptide hormone secretion	1
positive regulation of hormone secretion	1
regulation of peptide hormone secretion	1
tight junction assembly	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
transport	1
cellular process	1
protein binding	1
high-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
apical junction complex	1
cellular_component	1
cell-cell junction	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ILDR1	MARVELD2	Q8N4S9	855
ILDR1	CLDN14	O95500	580
ILDR1	TRA2A	Q13595	571
ILDR1	TMIE	Q8NEW7	571
ILDR1	OCLN	Q16625	555
ILDR1	TMPRSS3	P57727	545
ILDR1	MYO15A	Q9UKN7	543
ILDR1	TRA2B	P62995	536
ILDR1	TRIOBP	Q9H2D6	531
ILDR1	GRXCR1	A8MXD5	513
ILDR1	GIPC3	Q8TF64	512
ILDR1	TMC1	Q8TDI8	507
ILDR1	LOXHD1	Q8IVV2	506
ILDR1	PJVK	Q0ZLH3	505
ILDR1	CLDN12	P56749	495

IntAct

10 interactions, top by confidence:

A	B	Type	Score
FCGR2A	ILDR1	psi-mi:“MI:0915”(physical association)	0.400
FCGR1A	ILDR1	psi-mi:“MI:0915”(physical association)	0.400
IGDCC3	ILDR1	psi-mi:“MI:0915”(physical association)	0.400
IL6R	ILDR1	psi-mi:“MI:0915”(physical association)	0.400
ILDR1	LILRB1	psi-mi:“MI:0915”(physical association)	0.400
ILDR1	MXRA5	psi-mi:“MI:0915”(physical association)	0.400
ILDR1	PILRB	psi-mi:“MI:0915”(physical association)	0.400
ILDR1	NEDD4	psi-mi:“MI:0914”(association)	0.350
ILDR1	FBP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): NEDD4L (Affinity Capture-MS), NEDD4 (Affinity Capture-MS), ITCH (Affinity Capture-MS), WWP1 (Affinity Capture-MS), ILDR1 (Positive Genetic), NEDD4 (Affinity Capture-MS), WWP1 (Affinity Capture-MS), ITCH (Affinity Capture-MS), NEDD4L (Affinity Capture-MS), FBP1 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), HECW1 (Affinity Capture-MS), IDE (Affinity Capture-MS), HECW2 (Affinity Capture-MS), ILDR1 (Affinity Capture-MS)

ESM2 similar proteins: A1L3I3, A2CEX1, A2RUV4, B5TVM2, E1BLT8, E9PYH6, E9QDC5, O15047, O60504, O94875, P27715, P43322, Q148W8, Q1LY77, Q2THW0, Q2THW7, Q2THW8, Q2THW9, Q2THX0, Q2THX1, Q32NM7, Q3U5C7, Q5R7R7, Q5R838, Q5R8C7, Q5RD34, Q5VUB5, Q5VZP5, Q5Y5T5, Q6PEI3, Q71H61, Q71QF9, Q7Z3G6, Q80Y24, Q86SU0, Q86UR5, Q86X29, Q8CBR1, Q8N4C8, Q8VDZ4

Diamond homologs: B5TVM2, Q32NM7, Q5R8C7, Q71H61, Q86SU0, Q86X29, Q8CBR1, Q99KG5, Q9WU74

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	8
Uncertain significance	178
Likely benign	74
Benign	20

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1027551	NM_001199799.2(ILDR1):c.9G>A (p.Trp3Ter)	Pathogenic
1299309	NM_001199799.2(ILDR1):c.820C>T (p.Gln274Ter)	Pathogenic
1299310	NM_001199799.2(ILDR1):c.294del (p.Val99fs)	Pathogenic
1901581	NM_001199799.2(ILDR1):c.805C>T (p.Gln269Ter)	Pathogenic
2689866	NM_001199799.2(ILDR1):c.1180del (p.Glu394fs)	Pathogenic
2997314	NM_001199799.2(ILDR1):c.432C>G (p.Tyr144Ter)	Pathogenic
3001747	NM_001199799.2(ILDR1):c.279del (p.Asn93fs)	Pathogenic
30796	NM_001199799.2(ILDR1):c.1135G>T (p.Glu379Ter)	Pathogenic
30798	NM_001199799.2(ILDR1):c.583C>T (p.Gln195Ter)	Pathogenic
3253316	NM_001199799.2(ILDR1):c.2T>C (p.Met1Thr)	Pathogenic
3601172	NM_001199799.2(ILDR1):c.1141C>T (p.Gln381Ter)	Pathogenic
3601173	NM_001199799.2(ILDR1):c.102_105del (p.Arg33_Tyr34insTer)	Pathogenic
3601174	NM_001199799.2(ILDR1):c.247del (p.Ser83fs)	Pathogenic
3601175	NM_001199799.2(ILDR1):c.28del (p.Trp10fs)	Pathogenic
3664288	NM_001199799.2(ILDR1):c.1074del (p.Ser359fs)	Pathogenic
3718305	NM_001199799.2(ILDR1):c.720G>A (p.Trp240Ter)	Pathogenic
4807827	NM_001199799.2(ILDR1):c.316del (p.Arg106fs)	Pathogenic
627449	NM_001199799.2(ILDR1):c.643G>T (p.Glu215Ter)	Pathogenic
695027	NM_001199799.2(ILDR1):c.942C>A (p.Cys314Ter)	Pathogenic
3075920	NM_001199799.2(ILDR1):c.377del (p.Asn126fs)	Likely pathogenic
3345513	NM_001199799.2(ILDR1):c.755del (p.Pro252fs)	Likely pathogenic
3351313	NM_001199799.2(ILDR1):c.379C>T (p.Arg127Ter)	Likely pathogenic
3364315	NM_001199799.2(ILDR1):c.234C>A (p.Tyr78Ter)	Likely pathogenic
3601176	NM_001199799.2(ILDR1):c.353_357dup (p.Arg120fs)	Likely pathogenic
3601177	NM_001199799.2(ILDR1):c.98_99insAA (p.Tyr34fs)	Likely pathogenic
4081463	NM_001199799.2(ILDR1):c.810del (p.Met270fs)	Likely pathogenic
996672	NM_001199799.2(ILDR1):c.1137del (p.Glu379fs)	Likely pathogenic

SpliceAI

1038 predictions. Top by Δscore:

Variant	Effect	Δscore
3:121994314:C:CC	acceptor_gain	1.0000
3:122001738:CACT:C	donor_loss	1.0000
3:122001739:ACTTA:A	donor_loss	1.0000
3:122001740:CTTAC:C	donor_loss	1.0000
3:122001741:TTAC:T	donor_loss	1.0000
3:122001742:T:TC	donor_loss	1.0000
3:122001743:A:AC	donor_gain	1.0000
3:122001743:ACGT:A	donor_loss	1.0000
3:122001744:C:CG	donor_gain	1.0000
3:122001744:CG:C	donor_gain	1.0000
3:122001765:T:TA	donor_gain	1.0000
3:122001860:TGCTC:T	acceptor_gain	1.0000
3:122001862:CTC:C	acceptor_gain	1.0000
3:122001865:C:CC	acceptor_gain	1.0000
3:122001866:T:C	acceptor_loss	1.0000
3:122001868:C:CT	acceptor_gain	1.0000
3:122005240:TCA:T	donor_loss	1.0000
3:122005241:CAC:C	donor_loss	1.0000
3:122005242:A:AC	donor_gain	1.0000
3:122005243:C:CA	donor_gain	1.0000
3:122005243:CG:C	donor_gain	1.0000
3:122005243:CGG:C	donor_gain	1.0000
3:122005243:CGGT:C	donor_gain	1.0000
3:122005243:CGGTT:C	donor_gain	1.0000
3:122005390:TATG:T	acceptor_gain	1.0000
3:122005391:ATG:A	acceptor_gain	1.0000
3:122005392:TG:T	acceptor_gain	1.0000
3:122005394:C:CC	acceptor_gain	1.0000
3:122006985:ACTC:A	donor_loss	1.0000
3:122006987:TCACA:T	donor_loss	1.0000

AlphaMissense

3557 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:122001809:G:C	C145W	1.000
3:122001855:A:G	L130P	1.000
3:122007042:A:G	W60R	1.000
3:122007042:A:T	W60R	1.000
3:122001810:C:G	C145S	0.999
3:122001810:C:T	C145Y	0.999
3:122001811:A:G	C145R	0.999
3:122001811:A:T	C145S	0.999
3:122001822:C:T	G141E	0.999
3:122001828:T:A	D139V	0.999
3:122001828:T:G	D139A	0.999
3:122001829:C:G	D139H	0.999
3:122001833:C:A	W137C	0.999
3:122001833:C:G	W137C	0.999
3:122001855:A:T	L130H	0.999
3:122005264:C:G	R120P	0.999
3:122005265:G:T	R120S	0.999
3:122005324:C:G	R100P	0.999
3:122007023:C:G	C66S	0.999
3:122007023:C:T	C66Y	0.999
3:122007024:A:T	C66S	0.999
3:122007031:C:A	K63N	0.999
3:122007031:C:G	K63N	0.999
3:122007040:C:A	W60C	0.999
3:122007040:C:G	W60C	0.999
3:122007085:A:C	C45W	0.999
3:122007086:C:G	C45S	0.999
3:122007087:A:G	C45R	0.999
3:122007087:A:T	C45S	0.999
3:122001756:A:G	L163P	0.998

dbSNP variants (sampled 300 via entrez): RS1000031086 (3:122037237 C>A,G), RS1000045580 (3:122016646 T>A,C), RS1000076589 (3:122009320 T>A,G), RS1000089468 (3:121987383 T>G), RS1000128848 (3:122044666 A>G), RS1000163832 (3:122004719 A>G), RS1000219103 (3:122057809 T>G), RS1000231377 (3:122061269 T>C), RS1000285649 (3:122013348 T>C), RS1000322256 (3:122006922 A>G), RS1000369252 (3:121998350 T>G), RS1000404688 (3:122040861 T>C), RS1000430715 (3:121992152 T>C), RS1000482329 (3:122032559 C>T), RS1000499977 (3:122059190 G>A)

Disease associations

OMIM: gene MIM:609739 | disease phenotypes: MIM:609646, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 42	Definitive	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AR

Mondo (4): autosomal recessive nonsyndromic hearing loss 42 (MONDO:0012326), hearing loss disorder (MONDO:0005365), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (4): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare non-syndromic genetic deafness (Orphanet:87884), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0003593	Infantile onset
HP:0003680	Nonprogressive

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001341_9	Multiple sclerosis	2.000000e-07
GCST003340_3	Epstein Barr virus nuclear antigen 1 IgG levels or multiple sclerosis	5.000000e-08
GCST005986_5	Blood urea nitrogen levels	3.000000e-08
GCST007798_55	Asthma	7.000000e-09
GCST007800_97	Asthma (childhood onset)	1.000000e-10
GCST007932_16	Medication use (thyroid preparations)	4.000000e-11
GCST008062_82	Blood urea nitrogen levels	1.000000e-12
GCST009429_6	Age-related hearing impairment (high frequency)	1.000000e-09
GCST009597_283	Multiple sclerosis	7.000000e-43
GCST012442_15	Age-related hearing impairment	3.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007790	Epstein Barr virus nuclear antigen 1 IgG measurement
EFO:0009933	Thyroid preparation use measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C564609	Deafness, Autosomal Recessive (supp.)
C566460	Deafness, Autosomal Recessive 42 (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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, decreases expression	2
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Calcitriol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Paraoxon	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Vincristine	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound