TIMM8A

Summary

TIMM8A (translocase of inner mitochondrial membrane 8A, HGNC:11817) is a protein-coding gene on chromosome Xq22.1, encoding Mitochondrial import inner membrane translocase subunit Tim8 A (O60220). Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. It is a selective cancer dependency (DepMap: 36.2% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 1678 — RefSeq curated summary.

At a glance

• Gene–disease (curated): deafness dystonia syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 82 total — 20 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 55
• Cancer dependency (DepMap): dependent in 36.2% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004085

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11817
Approved symbol	TIMM8A
Name	translocase of inner mitochondrial membrane 8A
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	DDP, MTS
Ensembl gene	ENSG00000126953
Ensembl biotype	protein_coding
OMIM	300356
Entrez	1678

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000372902, ENST00000644112, ENST00000645279, ENST00000647480, ENST00000894322, ENST00000940410, ENST00000940411

RefSeq mRNA: 2 — MANE Select: NM_004085 NM_001145951, NM_004085

CCDS: CCDS14481, CCDS87768

Canonical transcript exons

ENST00000372902 — 2 exons

Exon	Start	End
ENSE00001458951	101345661	101346660
ENSE00001839344	101348533	101348742

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 93.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3166 / max 221.5980, expressed in 1736 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199947	13.3166	1736

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	93.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.63	gold quality
mucosa of transverse colon	UBERON:0004991	83.09	gold quality
cortical plate	UBERON:0005343	82.22	gold quality
right lobe of liver	UBERON:0001114	82.09	gold quality
islet of Langerhans	UBERON:0000006	80.65	gold quality
heart left ventricle	UBERON:0002084	80.56	gold quality
cardiac ventricle	UBERON:0002082	80.02	gold quality
rectum	UBERON:0001052	79.52	gold quality
muscle of leg	UBERON:0001383	79.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.34	gold quality
gastrocnemius	UBERON:0001388	79.31	gold quality
stromal cell of endometrium	CL:0002255	79.00	gold quality
prefrontal cortex	UBERON:0000451	78.85	gold quality
ventricular zone	UBERON:0003053	78.65	gold quality
apex of heart	UBERON:0002098	78.58	gold quality
ganglionic eminence	UBERON:0004023	78.13	gold quality
right atrium auricular region	UBERON:0006631	77.88	gold quality
esophagus mucosa	UBERON:0002469	77.73	gold quality
heart	UBERON:0000948	77.56	gold quality
adrenal tissue	UBERON:0018303	77.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.05	gold quality
liver	UBERON:0002107	76.87	gold quality
monocyte	CL:0000576	76.67	gold quality
hair follicle	UBERON:0002073	76.49	silver quality
mononuclear cell	CL:0000842	76.43	gold quality
leukocyte	CL:0000738	76.38	gold quality
lower esophagus mucosa	UBERON:0035834	76.24	gold quality
esophagus squamous epithelium	UBERON:0006920	76.14	silver quality
right adrenal gland	UBERON:0001233	75.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting TIMM8A, 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-513B-5P	99.99	69.96	2150
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-10522-5P	99.26	68.50	2087

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 36.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Interaction of TIMM8a with the signal transduction adaptor molecule STAM1. (PMID:12745081)
• Intronic mutations in the DDP1 gene can also cause X-linked dystonia-deafness syndrome. (PMID:15710860)
• Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death. (PMID:16332536)
• Mutation in TIMM8a is associated with deafness-dystonia (Mohr-Tranebjaerg) syndrome (PMID:16411215)
• A sporadic 42-year-old man with MTS presenting with postlingual deafness, adult-onset progressive dystonia with marked arm tremor, mild spasticity of the legs, and visual disturbance due to a novel mutation in the DDP1 gene. (PMID:17534980)
• mRNA expression demonstrate increased TIMM8A mRNA levels in cultured fibroblasts from a patient with Mohr-Tranebjaerg Syndrome. (PMID:17999202)
• knockdown of the TIMM8A gene by RNA interference did not show an influence on the oxygen respiration rate and the mitochondrial membrane potentia (PMID:21984432)
• The results of this study demonistrated that the syndrome of deafness-dystonia is cause by mutation of Timm8a. (PMID:23418071)
• The authors show that human Tim8a is required for the assembly of Complex IV in neurons, which is mediated through a transient interaction with Complex IV assembly factors, in particular the copper chaperone COX17. (PMID:31682224)
• Frameshift mutation of Timm8a1 gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment. (PMID:32820032)
• Exploring the Oncogenic Potential of TIMM8A: A Crucial Factor in Breast Cancer Tumorigenesis. (PMID:38548519)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	timm8a	ENSDARG00000023672
mus_musculus	Timm8a1	ENSMUSG00000048007
rattus_norvegicus	Timm8a1	ENSRNOG00000064119

Paralogs (1): TIMM8B (ENSG00000150779)

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit Tim8 A — O60220 (reviewed: O60220)

Alternative names: Deafness dystonia protein 1, X-linked deafness dystonia protein

All UniProt accessions (2): O60220, A0A2R8YDA8

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. Probably necessary for normal neurologic development.

Subunit / interactions. Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Highly expressed in fetal and adult brain, followed by fetal lung, liver and kidney. Also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle and heart.

Disease relevance. Mohr-Tranebjaerg syndrome (MTS) [MIM:304700] An X-linked recessive disorder characterized by postlingual sensorineural deafness with onset in early childhood, dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane.

Similarity. Belongs to the small Tim family.

RefSeq proteins (2): NP_001139423, NP_004076* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004217	Tim10-like	Domain
IPR035427	Tim10-like_dom_sf	Homologous_superfamily

Pfam: PF02953

UniProt features (10 total): modified residue 4, disulfide bond 2, chain 1, short sequence motif 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60220-F1	87.07	0.74

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 (4): 57, 87, 94, 96

Disulfide bonds (2): 43–66, 47–62

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 349 (showing top): GGGACCA_MIR133A_MIR133B, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, PUJANA_CHEK2_PCC_NETWORK, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, MYCMAX_01, GGAANCGGAANY_UNKNOWN, USF_01, HFH4_01, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, HFH1_01, FUJII_YBX1_TARGETS_DN, BROWN_MYELOID_CELL_DEVELOPMENT_DN

GO Biological Process (4): nervous system development (GO:0007399), protein transport (GO:0015031), protein insertion into mitochondrial inner membrane (GO:0045039), obsolete protein targeting to mitochondrion (GO:0006626)

GO Molecular Function (3): identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial intermembrane space chaperone complex (GO:0042719), mitochondrial envelope (GO:0005740), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
inner mitochondrial membrane organization	1
mitochondrial protein import pathway	1
protein binding	1
cation binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrial intermembrane space	1
mitochondrial protein-containing complex	1
mitochondrion	1
organelle envelope	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMM8A	TIMM13	P62206	990
TIMM8A	TIMM9	Q9Y5J7	982
TIMM8A	TIMM10	P62072	972
TIMM8A	TIMM10B	Q9Y5J6	935
TIMM8A	CHCHD4	Q8N4Q1	931
TIMM8A	TIMM23	O14925	903
TIMM8A	SLC25A12	O75746	880
TIMM8A	SLC25A13	Q9UJS0	872
TIMM8A	TIMM17A	Q99595	797
TIMM8A	TIMM50	Q3ZCQ8	783
TIMM8A	SDHD	O14521	763
TIMM8A	DPP7	Q9UHL4	762
TIMM8A	TOMM40	O96008	679
TIMM8A	TIMM22	Q9Y584	665
TIMM8A	TOMM22	Q9NS69	656

IntAct

121 interactions, top by confidence:

A	B	Type	Score
STAM2	TIMM8A	psi-mi:“MI:0915”(physical association)	0.810
TIMM8A	STAM2	psi-mi:“MI:0915”(physical association)	0.810
TIMM8A	TIMM13	psi-mi:“MI:0915”(physical association)	0.740
TIMM8A	TIMM13	psi-mi:“MI:0407”(direct interaction)	0.740
KRT15	TIMM8A	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	KRT15	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
OIP5	TIMM8A	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	CAVIN3	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	TIMM8A	psi-mi:“MI:0407”(direct interaction)	0.560
TIMM8A	GLE1	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A		psi-mi:“MI:0915”(physical association)	0.560
BRK1	TIMM8A	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	CCT5	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (98): KRT15 (Two-hybrid), STAM2 (Two-hybrid), TIMM10 (Co-fractionation), TIMM8A (Co-fractionation), TIMM8A (Co-fractionation), TIMM8A (Co-fractionation), TIMM8A (Affinity Capture-MS), TIMM8A (Affinity Capture-MS), TIMM8A (Affinity Capture-MS), STAM (Two-hybrid), STAM2 (Two-hybrid), TIMM8A (Affinity Capture-MS), TIMM8A (Affinity Capture-MS), TIMM8A (Affinity Capture-MS), TIMM8A (Affinity Capture-MS)

ESM2 similar proteins: O45319, O60220, O74700, P0CR96, P0CR97, P0CS00, P0CS01, P57744, P57745, P62075, P62076, P62077, P62078, Q10481, Q3SZ93, Q3ZBS8, Q4I6B0, Q4PGT2, Q4X0V2, Q59MI8, Q59R24, Q5AZH4, Q616Q2, Q61TH2, Q66L32, Q6BHJ8, Q6BN23, Q6BU42, Q6C6Z2, Q6CIK7, Q6CJX3, Q6CM57, Q6DEM5, Q6DGJ3, Q6FK81, Q6FRE1, Q6FRT3, Q6GPY0, Q757S0, Q75DU7

Diamond homologs: O60220, P0CR94, P0CR95, P57744, P62075, P62076, P62077, P62078, Q3SZ93, Q3ZBS8, Q4FZG7, Q4I6B0, Q59MI8, Q616Q2, Q66L32, Q6BN23, Q6CWH5, Q6DEM5, Q6DGJ3, Q6FK81, Q6GPY0, Q75DU7, Q8AVK1, Q90YI5, Q9N408, Q9VTN3, Q9WVA1, Q9WVA2, Q9XGY4, Q9Y1A3, Q9Y5J9, Q9Y5L4, Q9Y8C0, O45319, Q09783, Q4IJW4, Q3SZW4, Q5RDJ0, Q6BHJ3, Q6CIK7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	4
Uncertain significance	15
Likely benign	19
Benign	8

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
11318	NM_004085.4(TIMM8A):c.116del (p.Met39fs)	Pathogenic
11319	NM_004085.4(TIMM8A):c.148_157del (p.Lys50fs)	Pathogenic
11320	NM_004085.4(TIMM8A):c.70G>T (p.Glu24Ter)	Pathogenic
11322	NM_004085.4(TIMM8A):c.73del (p.Glu24_Val25insTer)	Pathogenic
11324	NM_004085.4(TIMM8A):c.238C>T (p.Arg80Ter)	Pathogenic
11325	NM_004085.4(TIMM8A):c.133-23A>C	Pathogenic
11326	NM_004085.4(TIMM8A):c.127del (p.Cys43fs)	Pathogenic
1185085	NM_004085.4(TIMM8A):c.66_67del (p.Ile23fs)	Pathogenic
1312519	NC_000023.11:g.101345283_101347393del	Pathogenic
1686260	NM_004085.4(TIMM8A):c.181del (p.Ala61fs)	Pathogenic
1703041	NM_004085.4(TIMM8A):c.223C>T (p.Gln75Ter)	Pathogenic
21393	NM_004085.4(TIMM8A):c.112C>T (p.Gln38Ter)	Pathogenic
3601877	NM_004085.4(TIMM8A):c.132G>A (p.Trp44Ter)	Pathogenic
3601878	NM_004085.4(TIMM8A):c.133-1G>A	Pathogenic
3601880	NM_004085.4(TIMM8A):c.153_223dup (p.Gln75delinsLeuGlyGlnSerTrpThrValGlyLeuArgProValLeuTer)	Pathogenic
3601881	NM_004085.4(TIMM8A):c.217dup (p.Thr73fs)	Pathogenic
3601882	NM_004085.4(TIMM8A):c.28del (p.Ala10fs)	Pathogenic
4686644	NM_004085.4(TIMM8A):c.58C>T (p.Gln20Ter)	Pathogenic
929951	NC_000023.11:g.(?101346475)(101348757_?)del	Pathogenic
987116	NM_004085.4(TIMM8A):c.133-1G>T	Pathogenic
11321	NM_004085.4(TIMM8A):c.198C>G (p.Cys66Trp)	Likely pathogenic
1185678	NM_004085.4(TIMM8A):c.232_233insCAAT (p.Leu78fs)	Likely pathogenic
215260	NM_004085.4(TIMM8A):c.100C>T (p.Gln34Ter)	Likely pathogenic
804062	NM_004085.4(TIMM8A):c.127T>C (p.Cys43Arg)	Likely pathogenic

SpliceAI

431 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101346658:CTC:C	acceptor_gain	0.9800
X:101346661:C:CC	acceptor_gain	0.9800
X:101346661:CT:C	acceptor_loss	0.9800
X:101346696:T:C	acceptor_gain	0.9800
X:101348055:CACCA:C	donor_gain	0.9800
X:101348072:CTGGG:C	donor_gain	0.9800
X:101348525:CTCCT:C	donor_loss	0.9800
X:101348527:CCTCA:C	donor_loss	0.9800
X:101348528:CTCA:C	donor_loss	0.9800
X:101348529:TCA:T	donor_loss	0.9800
X:101348531:A:AT	donor_loss	0.9800
X:101348532:C:G	donor_loss	0.9800
X:101348532:CCCAA:C	donor_gain	0.9800
X:101348531:A:AC	donor_gain	0.9700
X:101348531:AC:A	donor_gain	0.9700
X:101348532:C:CC	donor_gain	0.9700
X:101348532:CC:C	donor_gain	0.9700
X:101348550:T:C	donor_gain	0.9700
X:101346671:CAAGA:C	acceptor_loss	0.9600
X:101348071:A:AC	donor_gain	0.9600
X:101348072:C:CC	donor_gain	0.9600
X:101348231:TGGTG:T	donor_gain	0.9600
X:101346666:C:CT	acceptor_gain	0.9500
X:101348265:G:A	donor_gain	0.9500
X:101348059:A:AC	donor_gain	0.9400
X:101348060:C:CC	donor_gain	0.9400
X:101348089:A:AC	donor_gain	0.9400
X:101348312:AGT:A	donor_gain	0.9400
X:101348253:TCA:T	donor_gain	0.9300
X:101348536:A:C	donor_gain	0.9300

AlphaMissense

645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101346587:C:G	R69P	0.999
X:101348533:C:A	W44C	0.999
X:101348533:C:G	W44C	0.999
X:101346596:C:T	C66Y	0.998
X:101348536:A:C	C43W	0.998
X:101348537:C:T	C43Y	0.998
X:101346554:C:G	R80P	0.997
X:101346583:G:C	F70L	0.997
X:101346583:G:T	F70L	0.997
X:101346585:A:G	F70L	0.997
X:101346593:A:T	V67D	0.997
X:101346595:G:C	C66W	0.997
X:101346596:C:A	C66F	0.997
X:101346597:A:G	C66R	0.997
X:101346608:C:T	C62Y	0.997
X:101346609:A:G	C62R	0.997
X:101346653:C:G	C47S	0.997
X:101346654:A:G	C47R	0.997
X:101346654:A:T	C47S	0.997
X:101348535:A:G	W44R	0.997
X:101348535:A:T	W44R	0.997
X:101346571:G:C	S74R	0.996
X:101346571:G:T	S74R	0.996
X:101346573:T:G	S74R	0.996
X:101348537:C:A	C43F	0.996
X:101348538:A:G	C43R	0.996
X:101348561:A:G	L35P	0.996
X:101346575:G:T	T73K	0.995
X:101346584:A:G	F70S	0.995
X:101346608:C:G	C62S	0.995

dbSNP variants (sampled 300 via entrez): RS1002649670 (X:101350618 C>T), RS1008503690 (X:101345378 A>G), RS1008904669 (X:101349094 G>A,C), RS1011332837 (X:101347999 G>A,T), RS1012369205 (X:101347094 A>G), RS1013119882 (X:101349339 G>A,T), RS1015796234 (X:101345393 G>T), RS1018764406 (X:101348147 A>T), RS1021684192 (X:101350737 G>A,C), RS1022550116 (X:101350021 G>C), RS1022705807 (X:101349347 C>A), RS1027072025 (X:101345442 C>T), RS1028956884 (X:101348026 C>T), RS1029423353 (X:101348651 G>A,C), RS1030013192 (X:101345347 C>T)

Disease associations

OMIM: gene MIM:300356 | disease phenotypes: MIM:304700, MIM:609129

GenCC curated gene-disease

Disease	Classification	Inheritance
deafness dystonia syndrome	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
deafness dystonia syndrome	Definitive	XL

Mondo (2): deafness dystonia syndrome (MONDO:0010578), auditory neuropathy (MONDO:0021944)

Orphanet (1): Mohr-Tranebjaerg syndrome (Orphanet:52368)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000375	Abnormal cochlea morphology
HP:0000399	Prelingual sensorineural hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000545	Myopia
HP:0000551	Color vision defect
HP:0000572	Visual loss
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000708	Atypical behavior
HP:0000726	Dementia
HP:0000751	Personality changes
HP:0000763	Sensory neuropathy
HP:0001133	Constriction of peripheral visual field
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001419	X-linked recessive inheritance
HP:0001751	Abnormal vestibular function
HP:0002015	Dysphagia
HP:0002172	Postural instability
HP:0002186	Apraxia

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C538268	Auditory neuropathy (supp.)
C535808	Mohr-Tranebjaerg syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Tretinoin	decreases expression	3
Cyclosporine	decreases expression	3
bisphenol A	increases expression	2
Leflunomide	decreases expression	2
Valproic Acid	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression, increases methylation	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	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, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	increases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Selenium	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS37	HAP1 TIMM8A (-) 1	Cancer cell line	Male
CVCL_XU24	HAP1 TIMM8A (-) 2	Cancer cell line	Male
CVCL_XU25	HAP1 TIMM8A (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02281006	PHASE2	TERMINATED	Efficacy of Trans-tympanic Injections of a Sodium Thiosulfate Gel to Prevent Cisplatin-induced Ototoxicity
NCT04187911	Not specified	RECRUITING	Relationships in Good Hands - Clinical and Cost-effectiveness of Dyadic Developmental Psychotherapy
NCT04763720	Not specified	ENROLLING_BY_INVITATION	Implementing Dyadic Developmental Psychotherapy (DDP) - Evaluation Research
NCT07032038	PHASE1/PHASE2	NOT_YET_RECRUITING	First In Human Randomised Trial of Rincell-1 in Adults With a Cochlear Implant
NCT01023932	Not specified	COMPLETED	Auditory Neuropathy and Cochlear Implants
NCT05666466	Not specified	UNKNOWN	Noninvasive Diagnostic Techniques in Determination of Site of Lesion of Auditory Neuropathy Spectrum Disorder
NCT06125015	Not specified	COMPLETED	Unexpected ABR Results in Patients Suspected With Auditory Neuropathy Spectrum Disorder