CLIC6

Summary

CLIC6 (CLIC family member 6, HGNC:2065) is a protein-coding gene on chromosome 21q22.12, encoding Chloride intracellular channel protein 6 (Q96NY7). In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.

This gene encodes a member of the chloride intracellular channel family of proteins. The gene is part of a large triplicated region found on chromosomes 1, 6, and 21. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 54102 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 395 total — 10 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_053277

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2065
Approved symbol	CLIC6
Name	CLIC family member 6
Location	21q22.12
Locus type	gene with protein product
Status	Approved
Aliases	CLIC5
Ensembl gene	ENSG00000159212
Ensembl biotype	protein_coding
OMIM	615321
Entrez	54102

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000349499, ENST00000360731, ENST00000954659

RefSeq mRNA: 2 — MANE Select: NM_053277 NM_001317009, NM_053277

CCDS: CCDS13638, CCDS82669

Canonical transcript exons

ENST00000349499 — 6 exons

Exon	Start	End
ENSE00001044021	34708700	34708806
ENSE00001044034	34709357	34709538
ENSE00001044048	34707944	34708069
ENSE00002449170	34707280	34707389
ENSE00003904437	34668994	34670762
ENSE00003907791	34716321	34718223

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6413 / max 231.3026, expressed in 295 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188937	1.4885	277
188935	0.0919	47
188936	0.0609	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.52	gold quality
bronchial epithelial cell	CL:0002328	99.44	gold quality
bronchus	UBERON:0002185	98.89	gold quality
nasal cavity epithelium	UBERON:0005384	98.86	gold quality
caput epididymis	UBERON:0004358	97.63	gold quality
palpebral conjunctiva	UBERON:0001812	95.18	gold quality
epithelium of nasopharynx	UBERON:0001951	94.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.38	gold quality
nasal cavity mucosa	UBERON:0001826	94.12	gold quality
epithelial cell of pancreas	CL:0000083	93.59	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	93.57	gold quality
pancreatic ductal cell	CL:0002079	91.14	silver quality
cardia of stomach	UBERON:0001162	90.66	gold quality
body of stomach	UBERON:0001161	89.41	gold quality
visceral pleura	UBERON:0002401	89.04	gold quality
trachea	UBERON:0003126	88.92	gold quality
stomach	UBERON:0000945	88.20	gold quality
urethra	UBERON:0000057	87.87	gold quality
parotid gland	UBERON:0001831	87.47	gold quality
fundus of stomach	UBERON:0001160	86.94	gold quality
amniotic fluid	UBERON:0000173	86.61	gold quality
right uterine tube	UBERON:0001302	85.99	gold quality
pylorus	UBERON:0001166	85.44	gold quality
minor salivary gland	UBERON:0001830	84.73	gold quality
ileal mucosa	UBERON:0000331	84.18	gold quality
saliva-secreting gland	UBERON:0001044	83.86	gold quality
lower lobe of lung	UBERON:0008949	83.80	silver quality
cardiac muscle of right atrium	UBERON:0003379	81.66	silver quality
apex of heart	UBERON:0002098	81.58	gold quality
mouth mucosa	UBERON:0003729	79.71	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	309.11
E-GEOD-135922	yes	15.78
E-ANND-3	yes	5.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting CLIC6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7161-5P	99.68	68.92	1592

Cross-species orthologs

24 orthologs

Organism	Symbol	Gene ID
danio_rerio	clic6	ENSDARG00000099108
mus_musculus	Clic6	ENSMUSG00000022949
rattus_norvegicus	Clic6	ENSRNOG00000026870
drosophila_melanogaster	GstE12	FBGN0027590
drosophila_melanogaster	Clic	FBGN0030529
drosophila_melanogaster	GstT3	FBGN0031117
drosophila_melanogaster	GstE13	FBGN0033381
drosophila_melanogaster	GstE1	FBGN0034335
drosophila_melanogaster	GstE11	FBGN0034354
drosophila_melanogaster	GstT1	FBGN0050000
drosophila_melanogaster	GstT2	FBGN0050005
drosophila_melanogaster	GstE9	FBGN0063491
drosophila_melanogaster	GstE8	FBGN0063492
drosophila_melanogaster	GstE7	FBGN0063493
drosophila_melanogaster	GstE6	FBGN0063494
drosophila_melanogaster	GstE5	FBGN0063495
drosophila_melanogaster	GstE4	FBGN0063496
drosophila_melanogaster	GstE3	FBGN0063497
drosophila_melanogaster	GstE2	FBGN0063498
drosophila_melanogaster	GstE10	FBGN0063499
caenorhabditis_elegans	exc-4	WBGENE00001365
caenorhabditis_elegans		WBGENE00001371
caenorhabditis_elegans	gst-43	WBGENE00001791
caenorhabditis_elegans		WBGENE00021817

Paralogs (14): GSTO2 (ENSG00000065621), GSTT2 (ENSG00000099984), GSTZ1 (ENSG00000100577), GDAP1 (ENSG00000104381), CLIC5 (ENSG00000112782), GDAP1L1 (ENSG00000124194), GSTT2B (ENSG00000133433), GSTO1 (ENSG00000148834), CLIC2 (ENSG00000155962), CLIC4 (ENSG00000169504), CLIC3 (ENSG00000169583), CLIC1 (ENSG00000213719), EEF1G (ENSG00000254772), GSTT4 (ENSG00000276950)

Protein

Protein identifiers

Chloride intracellular channel protein 6 — Q96NY7 (reviewed: Q96NY7)

Alternative names: Glutaredoxin-like oxidoreductase CLIC6, Parchorin

All UniProt accessions (1): Q96NY7

UniProt curated annotations — full annotation on UniProt →

Function. In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor. Can insert into membranes and form voltage-dependent chloride-selective channels. The channel opens upon membrane depolarization at positive voltages and closes at negative membrane voltages. May play a critical role in water-secreting cells, possibly through the regulation of chloride ion transport.

Subunit / interactions. Monomer (soluble state). Interacts with dopamine receptors DRD2, DRD3 and DRD4.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Expressed in brain, placenta, pancreas, liver, lung, heart, kidney, liver, spleen, soleus muscle, and brown fat.

Post-translational modifications. Phosphorylated.

Activity regulation. Channel activity is redox- and pH-regulated. Inhibited by IAA-94.

Domain organisation. The active G-site contains a monothiol Cys-X-X-Ser motif which mediates glutathione-dependent redox catalysis. Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as a chloride channel. The redox status of the active cysteine in Cys-X-X-Cys/Ser motif likely determines the capacity to adopt a soluble or membrane-inserted state. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.

Similarity. Belongs to the chloride channel CLIC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96NY7-1	B	yes
Q96NY7-2	A

RefSeq proteins (2): NP_001303938, NP_444507* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002946	CLIC	Family
IPR010987	Glutathione-S-Trfase_C-like	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR053823	CLIC_N	Domain

Pfam: PF22441

Catalyzed reactions (Rhea), 1 shown:

• chloride(in) = chloride(out) (RHEA:29823)

UniProt features (34 total): repeat 13, compositionally biased region 9, modified residue 3, region of interest 2, chain 1, transmembrane region 1, domain 1, short sequence motif 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NY7-F1	60.24	0.19

Functional residue map

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

Post-translational modifications (3): 44, 397, 442

Mutagenesis-validated functional residues (1):

Position	Phenotype
648	decreases channel conductance and abolishes its dependence on ph.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 280 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, LFA1_Q6, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_INORGANIC_ANION_TRANSPORT, GOCC_MICROTUBULE_ORGANIZING_CENTER, GTGCCTT_MIR506, GOBP_CHLORIDE_TRANSPORT, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOCC_CENTROSOME, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (4): monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476)

GO Molecular Function (5): chloride channel activity (GO:0005254), oxidoreductase activity (GO:0016491), D2 dopamine receptor binding (GO:0031749), D3 dopamine receptor binding (GO:0031750), D4 dopamine receptor binding (GO:0031751)

GO Cellular Component (6): cytoplasm (GO:0005737), plasma membrane (GO:0005886), chloride channel complex (GO:0034707), extracellular exosome (GO:0070062), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dopamine receptor binding	3
cellular anatomical structure	2
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
catalytic activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
extracellular vesicle	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIC6	TPRN	Q4KMQ1	849
CLIC6	RDX	P35241	742
CLIC6	GRXCR2	A6NFK2	651
CLIC6	EZR	P15311	568
CLIC6	AKAP9	Q99996	496
CLIC6	TMC1	Q8TDI8	495
CLIC6	CFTR	P13569	480
CLIC6	ADGRV1	Q8WXG9	448
CLIC6	SLC26A5	P58743	434
CLIC6	CDH23	Q9H251	432
CLIC6	PCDH15	Q96QU1	432
CLIC6	USH2A	O75445	429
CLIC6	WFS1	O76024	409
CLIC6	CLCA2	Q9UQC9	402
CLIC6	KCNJ13	O60928	399

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CLIC4	CLIC2	psi-mi:“MI:0914”(association)	0.530
CLIC5	NME6	psi-mi:“MI:0914”(association)	0.350
CLIC6	ZNF234	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	TAF12	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	OXR1	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	PKM	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	MYO1E	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ALDH5A1	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	PGK1	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ARG2	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	TUBGCP5	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	FCGR1A	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	GFPT2	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ZNF439	psi-mi:“MI:0915”(physical association)	0.000
EEF1A1	CLIC6	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	UBE4A	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	NFE2L2	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ATRX	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	NISCH	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	CLIC4	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	LGI1	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ZNF18	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ACTB	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	HUWE1	psi-mi:“MI:0915”(physical association)	0.000
ZNF224	CLIC6	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	PPRC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): CLIC6 (Affinity Capture-MS), CLIC6 (Affinity Capture-MS), CLIC6 (Two-hybrid), CLIC6 (Two-hybrid), CLIC6 (Two-hybrid), CLIC6 (Reconstituted Complex), CLIC6 (Affinity Capture-MS), CLIC6 (Affinity Capture-MS), ZNF18 (Two-hybrid), PKM (Two-hybrid), MYO1E (Two-hybrid), NFE2L2 (Two-hybrid), UBE4A (Two-hybrid), FCGR1A (Two-hybrid), GFPT2 (Two-hybrid)

ESM2 similar proteins: A0A0U1RQG5, A1L429, A6NDE8, A6NER3, A6NGK3, E1AZ71, O08664, O60829, O75459, O76087, P0C2W7, P0CL80, P0CL81, P0CL82, P0DSO3, P0DTW1, P52651, P62521, P86478, P86479, P86480, P86481, P86496, Q13066, Q13069, Q13070, Q17QW4, Q28181, Q2T9P9, Q32PA2, Q4V321, Q4V326, Q5JQC4, Q5U2Y8, Q62100, Q63803, Q64256, Q6NT46, Q6X7S9, Q7Z2X7

Diamond homologs: O00299, O15247, O95833, P35526, Q29238, Q5E9B7, Q5M883, Q5R957, Q6MG61, Q811Q2, Q8BHB9, Q8BXK9, Q95MF9, Q96NY7, Q9D7P7, Q9EPT8, Q9N2G5, Q9NZA1, Q9QYB1, Q9XSA7, Q9Y696, Q9Z0W7, Q9Z1Q5, O45405, Q9VY78, P81124, Q9FRL8, B3FWR8, P57109, Q65XA0, Q67UK9, Q8LE52, Q9FG59, Q9FWR4, Q9VSL3, Q8WQA4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	2
Uncertain significance	231
Likely benign	79
Benign	39

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1075907	NC_000006.11:g.(?45296464)(46047979_?)del	Pathogenic
1321998	GRCh37/hg19 21p13-q22.3(chr21:1-48129895)x3	Pathogenic
160365	NM_016929.5(CLIC5):c.96T>A (p.Cys32Ter)	Pathogenic
2424231	NC_000021.8:g.(?36079578)(37133458_?)del	Pathogenic
3246086	NC_000006.11:g.(?45479963)(45923001_?)del	Pathogenic
3601021	NM_016929.5(CLIC5):c.535del (p.Asp179fs)	Pathogenic
4682976	GRCh37/hg19 21q22.11-22.12(chr21:35298071-36876005)x1	Pathogenic
59248	GRCh37/hg19 21q22.1(chr21:35292816-36834601)x3	Pathogenic
685844	GRCh37/hg19 21q22.11-22.12(chr21:35298070-36876005)x1	Pathogenic
812913	NC_000021.8:g.35304341_36865875del	Pathogenic
1341311	GRCh37/hg19 6p21.1(chr6:45284656-46157024)x3	Likely pathogenic
694310	NM_016929.5(CLIC5):c.644G>A (p.Trp215Ter)	Likely pathogenic

SpliceAI

881 predictions. Top by Δscore:

Variant	Effect	Δscore
21:34708803:GAGA:G	donor_gain	1.0000
21:34708805:GA:G	donor_gain	1.0000
21:34708807:G:GG	donor_gain	1.0000
21:34709355:A:AG	acceptor_gain	1.0000
21:34709356:G:GA	acceptor_gain	1.0000
21:34709356:GTTC:G	acceptor_gain	1.0000
21:34709449:G:GT	donor_gain	1.0000
21:34709465:G:GT	donor_gain	1.0000
21:34709469:G:GT	donor_gain	1.0000
21:34709563:TGCC:T	donor_gain	1.0000
21:34709564:GCCG:G	donor_gain	1.0000
21:34716315:TTTCA:T	acceptor_loss	1.0000
21:34716316:TTCAG:T	acceptor_loss	1.0000
21:34716317:TCAGA:T	acceptor_loss	1.0000
21:34716318:CAG:C	acceptor_loss	1.0000
21:34716319:A:AG	acceptor_gain	1.0000
21:34716319:A:AT	acceptor_loss	1.0000
21:34716320:G:GA	acceptor_loss	1.0000
21:34716320:G:GG	acceptor_gain	1.0000
21:34716320:GATT:G	acceptor_gain	1.0000
21:34675143:ATTTG:A	acceptor_gain	0.9900
21:34707278:AGGCT:A	acceptor_gain	0.9900
21:34707279:GGCTG:G	acceptor_gain	0.9900
21:34708066:CGAGG:C	donor_loss	0.9900
21:34708067:GAGGT:G	donor_loss	0.9900
21:34708068:AGGT:A	donor_loss	0.9900
21:34708070:GTA:G	donor_loss	0.9900
21:34708071:T:G	donor_loss	0.9900
21:34708698:A:G	acceptor_gain	0.9900
21:34708802:TGAGA:T	donor_gain	0.9900

AlphaMissense

4493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:34708755:T:C	F574L	1.000
21:34708757:T:A	F574L	1.000
21:34708757:T:G	F574L	1.000
21:34709513:T:C	L643P	1.000
21:34709525:T:C	L647P	1.000
21:34707316:T:C	F489L	0.999
21:34707318:T:A	F489L	0.999
21:34707318:T:G	F489L	0.999
21:34707331:T:C	F494L	0.999
21:34707333:T:A	F494L	0.999
21:34707333:T:G	F494L	0.999
21:34707343:T:A	W498R	0.999
21:34707343:T:C	W498R	0.999
21:34707347:T:C	L499P	0.999
21:34707350:A:T	K500I	0.999
21:34707361:T:C	F504L	0.999
21:34707363:T:A	F504L	0.999
21:34707363:T:G	F504L	0.999
21:34707990:T:C	F529L	0.999
21:34707991:T:C	F529S	0.999
21:34707992:C:A	F529L	0.999
21:34707992:C:G	F529L	0.999
21:34708045:T:C	L547S	0.999
21:34708756:T:C	F574S	0.999
21:34708756:T:G	F574C	0.999
21:34708764:T:C	F577L	0.999
21:34708765:T:C	F577S	0.999
21:34708766:C:A	F577L	0.999
21:34708766:C:G	F577L	0.999
21:34708779:A:G	K582E	0.999

dbSNP variants (sampled 300 via entrez): RS1000039199 (21:34711610 C>T), RS1000068307 (21:34674952 G>A), RS1000096680 (21:34717734 G>A), RS1000176145 (21:34694353 C>T), RS1000276601 (21:34700912 C>G), RS1000276713 (21:34678488 A>G), RS1000328610 (21:34701699 A>C), RS1000437822 (21:34705964 A>C,G), RS1000484348 (21:34716650 T>C), RS1000615614 (21:34702145 T>A,G), RS1000737355 (21:34671950 T>C), RS1000827219 (21:34667810 A>C), RS1000845810 (21:34678310 C>A,T), RS1000972449 (21:34689688 C>T), RS1001024837 (21:34689369 C>T)

Disease associations

OMIM: gene MIM:615321 | disease phenotypes: MIM:616042, MIM:601399, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive	Supportive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 103	Limited	Autosomal recessive

Mondo (7): hearing loss disorder (MONDO:0005365), autosomal recessive nonsyndromic hearing loss 103 (MONDO:0014469), myoepithelial tumor (MONDO:0002380), hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (MONDO:0100083), hearing loss, autosomal recessive (MONDO:0019588), thrombocytopenia (MONDO:0002049), hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Orphanet (3): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Familial platelet disorder with associated myeloid malignancy (Orphanet:71290), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001751	Abnormal vestibular function
HP:0008568	Vestibular areflexia
HP:0011463	Childhood onset

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001588_3	Periodontal microbiota	1.000000e-06
GCST002874_37	Psoriasis	1.000000e-06
GCST004861_87	Itch intensity from mosquito bite	9.000000e-11
GCST004863_121	Mosquito bite size	2.000000e-11
GCST006412_58	Intraocular pressure	6.000000e-09
GCST006585_1731	Blood protein levels	2.000000e-10
GCST006979_285	Heel bone mineral density	2.000000e-11
GCST006988_71	Blond vs. brown/black hair color	6.000000e-10
GCST007001_4	Cerebrospinal AB1-42 levels in normal cognition	7.000000e-07
GCST007009_8	Hippocampal volume	2.000000e-07
GCST008159_19	Waist-to-hip ratio adjusted for BMI	6.000000e-06
GCST008748_4	Epigenetic age acceleration in alcohol use disorder	8.000000e-06
GCST009665_21	Breast cancer	2.000000e-09
GCST009798_46	Asthma	5.000000e-11
GCST010273_9	Gout (normal type)	8.000000e-07
GCST011116_4	Coronary artery disease in type 1 diabetes	7.000000e-07
GCST011741_14	LDL cholesterol levels in HIV infection	5.000000e-06
GCST011741_76	LDL cholesterol levels in HIV infection	5.000000e-06

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0005035	hippocampal volume
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0000473	epigenetic status
EFO:0022597	aging
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D009208	Myoepithelioma	C04.557.435.585
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C564609	Deafness, Autosomal Recessive (supp.)
C563324	Platelet Disorder, Familial, with Associated Myeloid Malignancy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
entinostat	affects cotreatment, increases expression	2
Decitabine	decreases expression, decreases reaction, affects expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, decreases reaction	2
bisphenol F	increases methylation	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects expression	1
Fonofos	increases methylation	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Parathion	increases methylation	1
Polychlorinated Biphenyls	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Genistein	increases expression	1

Clinical trials (associated diseases)

300 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
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
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss