THOC1

Summary

THOC1 (THO complex subunit 1, HGNC:19070) is a protein-coding gene on chromosome 18p11.32, encoding THO complex subunit 1 (Q96FV9). Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is a common-essential gene (DepMap: required in 96.8% of cancer cell lines).

Predicted to enable DNA binding activity and RNA binding activity. Involved in mRNA export from nucleus. Located in chromosome, telomeric region; cytoplasm; and nuclear speck. Part of THO complex part of transcription export complex. Implicated in autosomal dominant nonsyndromic deafness 86.

Source: NCBI Gene 9984 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss disorder (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 74 total — 2 pathogenic
• Phenotypes (HPO): 6
• Cancer dependency (DepMap): dependent in 96.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19070
Approved symbol	THOC1
Name	THO complex subunit 1
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	P84, HPR1
Ensembl gene	ENSG00000079134
Ensembl biotype	protein_coding
OMIM	606930
Entrez	9984

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 11 retained_intron, 9 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261600, ENST00000577429, ENST00000577552, ENST00000578224, ENST00000578529, ENST00000579232, ENST00000579891, ENST00000580038, ENST00000580544, ENST00000580870, ENST00000581116, ENST00000581269, ENST00000581576, ENST00000582313, ENST00000583228, ENST00000584470, ENST00000584642, ENST00000585307, ENST00000631280, ENST00000884131, ENST00000940191, ENST00000940192, ENST00000940193, ENST00000958666

RefSeq mRNA: 1 — MANE Select: NM_005131 NM_005131

CCDS: CCDS45820

Canonical transcript exons

ENST00000261600 — 21 exons

Exon	Start	End
ENSE00003467304	264026	264092
ENSE00003467725	224924	224994
ENSE00003468887	215429	215504
ENSE00003475334	252539	252612
ENSE00003485335	226801	226901
ENSE00003503147	223440	223505
ENSE00003545605	246324	246455
ENSE00003548179	254273	254355
ENSE00003553882	267966	268047
ENSE00003555243	214520	214921
ENSE00003577033	247849	247957
ENSE00003585480	259682	259730
ENSE00003586229	259180	259275
ENSE00003588408	225337	225403
ENSE00003601413	265457	265530
ENSE00003612845	265303	265363
ENSE00003622355	225089	225139
ENSE00003653987	224084	224179
ENSE00003656092	218886	218969
ENSE00003674082	260186	260304
ENSE00003784389	216486	216633

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1622 / max 442.4410, expressed in 1780 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170933	20.1622	1780

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.59	gold quality
cerebellar hemisphere	UBERON:0002245	95.75	gold quality
cerebellar cortex	UBERON:0002129	95.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.44	gold quality
right uterine tube	UBERON:0001302	95.40	gold quality
adenohypophysis	UBERON:0002196	95.38	gold quality
corpus callosum	UBERON:0002336	95.31	gold quality
left ovary	UBERON:0002119	95.30	gold quality
left lobe of thyroid gland	UBERON:0001120	95.22	gold quality
body of pancreas	UBERON:0001150	95.16	gold quality
tendon	UBERON:0000043	95.14	gold quality
nerve	UBERON:0001021	95.07	gold quality
tibial nerve	UBERON:0001323	95.07	gold quality
right lobe of thyroid gland	UBERON:0001119	95.06	gold quality
endocervix	UBERON:0000458	95.02	gold quality
thyroid gland	UBERON:0002046	94.95	gold quality
right ovary	UBERON:0002118	94.94	gold quality
pituitary gland	UBERON:0000007	94.85	gold quality
body of uterus	UBERON:0009853	94.73	gold quality
cerebellum	UBERON:0002037	94.61	gold quality
skin of abdomen	UBERON:0001416	94.58	gold quality
right testis	UBERON:0004534	94.54	gold quality
left testis	UBERON:0004533	94.53	gold quality
sural nerve	UBERON:0015488	94.53	gold quality
skin of leg	UBERON:0001511	94.35	gold quality
mucosa of stomach	UBERON:0001199	94.21	gold quality
tendon of biceps brachii	UBERON:0008188	94.10	gold quality
ectocervix	UBERON:0012249	93.87	gold quality
ovary	UBERON:0000992	93.77	gold quality
lower esophagus mucosa	UBERON:0035834	93.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, FOXC1, NFE2L2, NFKB, RELA

miRNA regulators (miRDB)

13 targeting THOC1, 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-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-5701	98.97	69.54	1502

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• hHpr1/p84/Thoc1 regulates transcriptional elongation and may participate in a protein complex functionally analogous to yeast TREX, physically linking elongating RNA polymerase II with RNA processing factors (PMID:15870275)
• recruitment of the human TREX complex to spliced mRNA is not directly coupled to transcription, but is instead coupled to transcription indirectly through splicing (PMID:15998806)
• Thoc1 may be important for neoplastic transformation (PMID:17638875)
• Cells respond to AAV infection by activating two DNA damage signaling cascades. The first activates the p84N5 protein, which in turn activates caspase-6, leading to cell death. (PMID:17699767)
• elevated expression of hHpr1/p84/Thoc1 is common in NSCLC and may have prognostic significance in subgroups of patients (PMID:18469354)
• A differential connection between tumorogenesis and the expression levels of human THO and ALY. (PMID:21329510)
• We show that human THO depletion impairs transcription elongation and mRNA export and increases instability associated with DNA breaks, leading to hyper-recombination and gammaH2AX and 53BP1 foci accumulation (PMID:22144908)
• overexpression of hTREX84 is associated with cancer cell transformation, proliferation and may be regulated by RelA/p65 (PMID:22952718)
• This suggests NEDD4-1 functions in conjunction with other post-translational mechanisms to regulate Thoc1 protein and THO activity. (PMID:23460917)
• Thoc1 inhibits cell growth via induction of cell cycle arrest and apoptosis in lung cancer cells. (PMID:24682263)
• In humans, high THOC1 protein expression associates with prostate cancer aggressiveness and recurrence. Thus, THOC1 protein is a molecular marker that may improve the identification of aggressive prostate cancers, potentially reducing overtreatment. (PMID:25296641)
• Colorectal cancer patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. (PMID:26545775)
• THO interacts with the Sin3A histone deacetylase complex to suppress co-transcriptional R-loops, DNA damage, and replication impairment. Functional analyses show that histone hypo-acetylation prevents accumulation of harmful R-loops and RNA-mediated genomic instability. (PMID:29074626)
• Knockdown of THOC1 reduces the proliferation of hepatocellular carcinoma and increases the sensitivity to cisplatin. (PMID:32669125)
• THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis. (PMID:32776944)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	thoc1	ENSDARG00000088246
mus_musculus	Thoc1	ENSMUSG00000024287
rattus_norvegicus	Thoc1	ENSRNOG00000015332
rattus_norvegicus	Da2-19	ENSRNOG00000032739
drosophila_melanogaster	Hpr1	FBGN0037382
caenorhabditis_elegans		WBGENE00020172

Protein

Protein identifiers

THO complex subunit 1 — Q96FV9 (reviewed: Q96FV9)

Alternative names: Nuclear matrix protein p84, hTREX84

All UniProt accessions (6): Q96FV9, J3KRD7, J3KT14, J3QQZ3, R4GMN4, R4GN58

UniProt curated annotations — full annotation on UniProt →

Function. Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. Required for efficient export of polyadenylated RNA. The THOC1-THOC2-THOC3 core complex alone is sufficient to bind export factor NXF1-NXT1 and promote ATPase activity of DDX39B/UAP56. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5’ end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. Regulates transcriptional elongation of a subset of genes. Involved in genome stability by preventing co-transcriptional R-loop formation. May play a role in hair cell formation, hence may be involved in hearing. Participates in an apoptotic pathway which is characterized by activation of caspase-6, increases in the expression of BAK1 and BCL2L1 and activation of NF-kappa-B. This pathway does not require p53/TP53, nor does the presence of p53/TP53 affect the efficiency of cell killing. Activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. Apoptosis is inhibited by association with RB1. (Microbial infection) The TREX complex is essential for the export of Kaposi’s sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.

Subunit / interactions. Component of the THO subcomplex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7. The THO subcomplex interacts with DDX39B to form the THO-DDX39B complex which multimerizes into a 28-subunit tetrameric assembly. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; in the complex interacts with THOC2, THOC5 and THOC7. TREX seems to have a dynamic structure involving ATP-dependent remodeling. Binds to the hypophosphorylated form of RB1. Interacts with RNA polymerase II. Interacts with LUZP4.

Subcellular location. Nucleus speckle. Nucleus. Nucleoplasm. Nucleus matrix. Cytoplasm Cytoplasm.

Tissue specificity. Ubiquitous. Expressed in various cancer cell lines. Expressed at very low levels in normal breast epithelial cells and highly expressed in breast tumors. Expression is strongly associated with an aggressive phenotype of breast tumors and expression correlates with tumor size and the metastatic state of the tumor progression.

Post-translational modifications. Expression is altered specifically during apoptosis and is accompanied by the appearance of novel forms with smaller apparent molecular mass. Polyubiquitinated, leading to proteasomal degradation; probably involves NEDD4.

Disease relevance. Deafness, autosomal dominant, 86 (DFNA86) [MIM:620280] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss 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. DFNA86 is characterized by progressive, bilateral hearing loss that is most predominant in the high frequencies, begins mildly during the fourth decade and gradually progresses to severe-to-profound deafness in the seventh and eighth decades. Affected subjects have tinnitus, while vestibular dysfunction or other clinical abnormalities are not present. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. An intact death domain is needed for apoptosis.

Induction. Up-regulated during cell proliferation.

Miscellaneous. May be due to an intron retention.

Similarity. Belongs to the THOC1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96FV9-1	1	yes
Q96FV9-2	2, p84N5s

RefSeq proteins (1): NP_005122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR021861	THO_THOC1	Family

Pfam: PF00531, PF11957

UniProt features (70 total): helix 24, sequence conflict 9, modified residue 8, turn 7, cross-link 5, region of interest 4, strand 3, splice variant 2, mutagenesis site 2, compositionally biased region 2, chain 1, domain 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7APK	ELECTRON MICROSCOPY	3.3
7ZNL	ELECTRON MICROSCOPY	3.45
7ZNK	ELECTRON MICROSCOPY	3.9
8R7L	ELECTRON MICROSCOPY	4.12
1WXP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FV9-F1	80.87	0.42

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 (13): 2, 4, 133, 300, 537, 542, 560, 31, 408, 580, 595, 595, 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
617	loss of ability to induce apoptosis. interferes with normal response of saos-2 cells to radiation.
620	loss of ability to induce apoptosis. interferes with normal response of saos-2 cells to radiation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 163 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, CREB_Q4, GOBP_NUCLEAR_TRANSPORT, MODULE_331, CADWELL_ATG16L1_TARGETS_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_RNA_SPLICING, ATF3_Q6, CREB_Q2_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (6): mRNA processing (GO:0006397), mRNA export from nucleus (GO:0006406), apoptotic process (GO:0006915), signal transduction (GO:0007165), RNA splicing (GO:0008380), mRNA transport (GO:0051028)

GO Molecular Function (4): DNA binding (GO:0003677), RNA binding (GO:0003723), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): transcription export complex (GO:0000346), THO complex (GO:0000347), THO complex part of transcription export complex (GO:0000445), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	2
Transport of Mature Transcript to Cytoplasm	1
RNA Polymerase II Transcription	1
Metabolism of RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
nucleic acid binding	2
nuclear protein-containing complex	2
nuclear lumen	2
mRNA metabolic process	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
RNA transport	1
protein binding	1
binding	1
transcription export complex	1
THO complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
chromosomal region	1

Protein interactions and networks

STRING

1760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THOC1	THOC2	Q8NI27	999
THOC1	THOC3	Q96J01	999
THOC1	THOC7	Q6I9Y2	997
THOC1	THOC6	Q86W42	997
THOC1	THOC5	Q13769	996
THOC1	DDX39B	Q13838	995
THOC1	ALYREF	Q86V81	985
THOC1	CYLD	Q9NQC7	962
THOC1	GLI2	P10070	960
THOC1	SARNP	P82979	826
THOC1	RAE1	P78406	741
THOC1	FYTTD1	Q96QD9	740
THOC1	CHTOP	Q9Y3Y2	725
THOC1	SIN3A	Q96ST3	717
THOC1	POLDIP3	Q9BY77	708

IntAct

179 interactions, top by confidence:

A	B	Type	Score
THOC1	THOC5	psi-mi:“MI:0914”(association)	0.930
THOC1	THOC5	psi-mi:“MI:0915”(physical association)	0.930
THOC5	THOC1	psi-mi:“MI:0915”(physical association)	0.930
THOC1	THOC5	psi-mi:“MI:0403”(colocalization)	0.930
DDX39B	THOC5	psi-mi:“MI:0915”(physical association)	0.800
THOC1	MOAP1	psi-mi:“MI:0915”(physical association)	0.780
MOAP1	THOC1	psi-mi:“MI:0915”(physical association)	0.780
DDX39B	ALYREF	psi-mi:“MI:0914”(association)	0.770
DDX39A	DDX39B	psi-mi:“MI:0914”(association)	0.770
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
THOC2	THOC5	psi-mi:“MI:0914”(association)	0.730
ALYREF	THOC5	psi-mi:“MI:0914”(association)	0.710
THOC5	ALYREF	psi-mi:“MI:0914”(association)	0.710
THOC1	THOC1	psi-mi:“MI:0915”(physical association)	0.670
THOC1	EIF4A3	psi-mi:“MI:0914”(association)	0.660
THOC1	EIF4A3	psi-mi:“MI:0915”(physical association)	0.660
CHTOP	THOC5	psi-mi:“MI:0914”(association)	0.660

BioGRID (300): RABGEF1 (Two-hybrid), TRIM54 (Two-hybrid), MOAP1 (Two-hybrid), USHBP1 (Two-hybrid), THOC1 (Affinity Capture-MS), THOC1 (Affinity Capture-MS), THOC1 (Affinity Capture-MS), THOC1 (Affinity Capture-Western), THOC1 (Co-fractionation), THOC1 (Co-fractionation), THOC1 (Co-fractionation), THOC1 (Co-fractionation), THOC1 (Co-fractionation), THOC5 (Co-fractionation), THOC1 (Synthetic Growth Defect)

ESM2 similar proteins: A0A1S4D1D3, A0A1W2PR95, A0A8I6ASZ5, A8WE67, D2K8N5, D3Z8X7, D3ZND0, E1C760, E7EXT2, F6Y9J3, F7AEX0, O08836, O60308, P27641, P54729, P78318, Q0P4W3, Q14CX7, Q15021, Q2QY04, Q2YD98, Q3ZC62, Q4V8E4, Q5EAU9, Q61249, Q68FJ0, Q6NY52, Q6PBQ2, Q6PGY6, Q6QI44, Q7ZXA8, Q80V31, Q86VS3, Q8BWZ3, Q8C6E0, Q8C9J3, Q8IYW2, Q8K2Z4, Q8LDQ4, Q8LNU5

Diamond homologs: P59924, Q7SYB2, Q8R3N6, Q96FV9, Q13546, Q15628, Q1M161, Q2KI74, Q32NG6, Q3U0V2, Q60855, Q9I9N5, Q93VM9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
THOC1	“form complex”	“TREX complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA 3’-end processing	16	35.4×	4e-19
Transport of Mature Transcript to Cytoplasm	7	29.9×	1e-07
RNA Polymerase II Transcription Termination	11	27.1×	9e-12
Transport of Mature mRNA derived from an Intron-Containing Transcript	15	25.7×	1e-15
Processing of Capped Intron-Containing Pre-mRNA	21	19.4×	2e-19
mRNA Splicing	14	17.3×	3e-12
mRNA Splicing - Major Pathway	27	16.6×	2e-23
mRNA Polyadenylation	16	15.8×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	14	33.1×	2e-15
poly(A)+ mRNA export from nucleus	5	27.0×	2e-04
U2-type prespliceosome assembly	5	25.0×	2e-04
spliceosomal snRNP assembly	5	23.2×	3e-04
mRNA splicing, via spliceosome	26	19.1×	3e-23
RNA splicing	18	12.7×	1e-12
mRNA processing	17	10.7×	8e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	45
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2443955	NM_005131.3(THOC1):c.547C>G (p.Leu183Val)	Pathogenic
564564	GRCh37/hg19 18p11.32-11.21(chr18:136226-15198989)x1	Pathogenic

SpliceAI

3235 predictions. Top by Δscore:

Variant	Effect	Δscore
18:214917:AGGAC:A	acceptor_gain	1.0000
18:214918:GGAC:G	acceptor_gain	1.0000
18:214919:GAC:G	acceptor_gain	1.0000
18:214919:GACC:G	acceptor_loss	1.0000
18:214920:AC:A	acceptor_gain	1.0000
18:214920:ACC:A	acceptor_loss	1.0000
18:214921:CC:C	acceptor_gain	1.0000
18:214922:C:CC	acceptor_gain	1.0000
18:214929:A:AC	acceptor_gain	1.0000
18:214929:A:C	acceptor_gain	1.0000
18:215423:TCTTA:T	donor_loss	1.0000
18:215424:CTTA:C	donor_loss	1.0000
18:215425:TTA:T	donor_loss	1.0000
18:215426:TA:T	donor_loss	1.0000
18:215427:A:AC	donor_gain	1.0000
18:215427:ACTTT:A	donor_gain	1.0000
18:215428:C:CT	donor_gain	1.0000
18:215428:CT:C	donor_gain	1.0000
18:215428:CTT:C	donor_gain	1.0000
18:215428:CTTT:C	donor_gain	1.0000
18:215428:CTTTC:C	donor_gain	1.0000
18:215431:T:A	donor_gain	1.0000
18:215500:GGAGG:G	acceptor_gain	1.0000
18:215501:GAGG:G	acceptor_gain	1.0000
18:215502:AGG:A	acceptor_gain	1.0000
18:215503:GG:G	acceptor_gain	1.0000
18:215504:GC:G	acceptor_loss	1.0000
18:215505:C:CC	acceptor_gain	1.0000
18:215505:C:T	acceptor_loss	1.0000
18:216629:CAGCC:C	acceptor_gain	1.0000

AlphaMissense

4360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:216523:A:G	L522P	1.000
18:216523:A:T	L522H	1.000
18:216576:G:C	S504R	1.000
18:216576:G:T	S504R	1.000
18:216578:T:G	S504R	1.000
18:216587:C:G	A501P	1.000
18:216592:A:G	L499P	1.000
18:216594:T:A	R498S	1.000
18:216594:T:G	R498S	1.000
18:216595:C:A	R498I	1.000
18:216595:C:G	R498T	1.000
18:216598:A:G	L497P	1.000
18:216601:G:T	A496D	1.000
18:216602:C:G	A496P	1.000
18:216606:C:A	W494C	1.000
18:216606:C:G	W494C	1.000
18:216607:C:G	W494S	1.000
18:216608:A:G	W494R	1.000
18:216608:A:T	W494R	1.000
18:223486:A:G	W442R	1.000
18:223486:A:T	W442R	1.000
18:224944:G:C	C396W	1.000
18:224945:C:T	C396Y	1.000
18:224946:A:G	C396R	1.000
18:224956:T:A	K392N	1.000
18:224956:T:G	K392N	1.000
18:224957:T:A	K392I	1.000
18:224957:T:G	K392T	1.000
18:224958:T:C	K392E	1.000
18:224958:T:G	K392Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000153513 (18:229923 C>A,T), RS1000254630 (18:252101 T>C), RS1000342237 (18:233318 G>A,C), RS1000353012 (18:265047 C>A), RS1000363292 (18:258969 C>G), RS1000378339 (18:221787 T>G), RS1000396057 (18:233031 T>C), RS1000574012 (18:239985 C>T), RS1000583814 (18:251786 C>T), RS1000638857 (18:259004 T>A), RS1000680782 (18:269642 A>C,G), RS1000716569 (18:222858 ACTT>A), RS1000884515 (18:234048 C>T), RS1000984334 (18:226939 C>T), RS1000991007 (18:240611 A>G)

Disease associations

OMIM: gene MIM:606930 | disease phenotypes: MIM:620280

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss disorder	Moderate	Autosomal dominant
sensorineural hearing loss disorder	Limited	Autosomal dominant

Mondo (3): hearing loss, autosomal dominant 86 (MONDO:0859524), sensorineural hearing loss disorder (MONDO:0020678), hearing loss disorder (MONDO:0005365)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0001751	Abnormal vestibular function
HP:0003581	Adult onset
HP:0011390	Abnormal inner ear morphology

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000641_8	Bipolar disorder or major depressive disorder	4.000000e-06
GCST005867_12	Menarche (age at onset)	5.000000e-09
GCST005867_3	Menarche (age at onset)	1.000000e-09
GCST006865_17	Bipolar disorder	7.000000e-06
GCST006865_5	Bipolar disorder	7.000000e-06
GCST008839_485	Height	4.000000e-20
GCST010244_432	Triglyceride levels	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004530	triglyceride measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
beta-lapachone	decreases expression, increases expression	1
methylparaben	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
lei gong teng	increases expression	1
beta-methylcholine	affects 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
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Calcitriol	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7M0	SEES3-1V human THOC1, clone1	Embryonic stem cell	Male
CVCL_A7M1	SEES3-1V human THOC1, clone2	Embryonic stem cell	Male
CVCL_A7M2	SEES3-1V human THOC1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

298 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
NCT01655212	PHASE3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	PHASE3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	PHASE3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
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
NCT02497690	PHASE2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	PHASE2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	PHASE2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	PHASE2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
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
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
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
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
NCT02693704	PHASE2/PHASE3	COMPLETED	Evaluation of a Binaural Spatialization Method for Hearing Aids
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy