BDP1

Summary

BDP1 (BDP1 general transcription factor IIIB subunit, HGNC:13652) is a protein-coding gene on chromosome 5q13.2, encoding Transcription factor TFIIIB component B’’ homolog (A6H8Y1). General activator of RNA polymerase III transcription.

The product of this gene is a subunit of the TFIIIB transcription initiation complex, which recruits RNA polymerase III to target promoters in order to initiate transcription. The encoded protein localizes to concentrated aggregates in the nucleus, and is required for transcription from all three types of polymerase III promoters. It is phosphorylated by casein kinase II during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription.

Source: NCBI Gene 55814 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 670 total — 3 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_018429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13652
Approved symbol	BDP1
Name	BDP1 general transcription factor IIIB subunit
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	TFC5, KIAA1241, KIAA1689, HSA238520, TFIIIB150
Ensembl gene	ENSG00000145734
Ensembl biotype	protein_coding
OMIM	607012
Entrez	55814

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding

ENST00000358731, ENST00000508157, ENST00000508917, ENST00000514903, ENST00000525844

RefSeq mRNA: 1 — MANE Select: NM_018429 NM_018429

CCDS: CCDS43328

Canonical transcript exons

ENST00000358731 — 39 exons

Exon	Start	End
ENSE00000971955	71548682	71548745
ENSE00000971956	71549420	71549606
ENSE00002114958	71545039	71545219
ENSE00003460679	71539557	71539649
ENSE00003461065	71512241	71512428
ENSE00003466235	71504621	71504751
ENSE00003470436	71490984	71491131
ENSE00003476847	71559982	71560237
ENSE00003486475	71553116	71553320
ENSE00003487275	71532308	71532427
ENSE00003493524	71564754	71567820
ENSE00003493771	71539042	71539078
ENSE00003494405	71523939	71524323
ENSE00003501106	71455651	71456089
ENSE00003504819	71514944	71515122
ENSE00003515982	71509465	71511151
ENSE00003517712	71513185	71513407
ENSE00003518852	71495250	71495408
ENSE00003520981	71489404	71489682
ENSE00003524042	71562274	71562520
ENSE00003528443	71541454	71541682
ENSE00003535645	71502599	71502791
ENSE00003538017	71497270	71497426
ENSE00003546561	71542105	71542265
ENSE00003559209	71486484	71486627
ENSE00003562546	71461817	71461926
ENSE00003568099	71501562	71501653
ENSE00003577316	71522756	71522949
ENSE00003590959	71470395	71470489
ENSE00003594773	71544357	71544507
ENSE00003606682	71556886	71556925
ENSE00003614235	71483842	71483896
ENSE00003621212	71517322	71517452
ENSE00003644294	71466096	71466221
ENSE00003646169	71464058	71464117
ENSE00003654541	71467354	71467487
ENSE00003658051	71458579	71458855
ENSE00003659072	71516061	71516271
ENSE00003660424	71522289	71522490

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6362 / max 444.9620, expressed in 1774 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56864	12.3899	1768
56863	0.6487	338
56865	0.3641	167
56866	0.2335	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.95	gold quality
calcaneal tendon	UBERON:0003701	94.60	gold quality
colonic epithelium	UBERON:0000397	92.97	gold quality
corpus callosum	UBERON:0002336	92.28	gold quality
right uterine tube	UBERON:0001302	91.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.09	gold quality
cortical plate	UBERON:0005343	90.45	gold quality
tonsil	UBERON:0002372	89.49	gold quality
bone marrow cell	CL:0002092	88.90	gold quality
adrenal tissue	UBERON:0018303	87.92	gold quality
ventricular zone	UBERON:0003053	87.89	gold quality
endometrium	UBERON:0001295	86.67	gold quality
superior frontal gyrus	UBERON:0002661	86.06	gold quality
bone marrow	UBERON:0002371	85.98	gold quality
ganglionic eminence	UBERON:0004023	85.88	gold quality
cerebellar cortex	UBERON:0002129	84.98	gold quality
cerebellar hemisphere	UBERON:0002245	84.96	gold quality
cerebellum	UBERON:0002037	84.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.51	gold quality
skeletal muscle tissue	UBERON:0001134	84.02	gold quality
urinary bladder	UBERON:0001255	83.21	gold quality
primary visual cortex	UBERON:0002436	82.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.90	gold quality
uterine cervix	UBERON:0000002	82.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.47	gold quality
popliteal artery	UBERON:0002250	82.43	gold quality
tibial artery	UBERON:0007610	82.43	gold quality
lymph node	UBERON:0000029	82.24	gold quality
muscle tissue	UBERON:0002385	82.07	gold quality
fallopian tube	UBERON:0003889	81.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.03
E-MTAB-6386	no	156.11
E-ENAD-17	no	117.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting BDP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 7)

• Human BDP1 protein represents essential components of TFIIIC1 and TFIIIC1-like activities. (PMID:15096501)
• Maf1 occupancy of Pol III genes is inversely correlated with that of the initiation factor TFIIIB (subunit Bdp1) and Pol III (PMID:17499043)
• PTEN represses RNA polymerase III-dependent transcription by targeting the TFIIIB complex (PMID:18391023)
• Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. (PMID:24312468)
• Data indicate the crystal structure of a Brf2-TBP-Bdp1 complex bound to a DNA promoter. (PMID:28743884)
• DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability. (PMID:32504003)
• Somatic mutations of cancer-related genes PELP1 and BDP1 in colorectal cancers. (PMID:32853945)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:162472	ENSDARG00000058630
danio_rerio	bdp1	ENSDARG00000102375
mus_musculus	Bdp1	ENSMUSG00000049658
rattus_norvegicus	Bdp1	ENSRNOG00000017864
drosophila_melanogaster	Bdp1	FBGN0032512
caenorhabditis_elegans	vep-1	WBGENE00015091

Protein

Protein identifiers

Transcription factor TFIIIB component B’’ homolog — A6H8Y1 (reviewed: A6H8Y1)

Alternative names: Transcription factor IIIB 150, Transcription factor-like nuclear regulator

All UniProt accessions (3): A6H8Y1, H0YCV8, H7C5U4

UniProt curated annotations — full annotation on UniProt →

Function. General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site.

Subunit / interactions. Component of TFIIIB complex. The TFIIIB complex has two activities, alpha and beta. The TFIIIB-alpha and TFIIIB-beta activities are required for transcription of genes with TFIIIC-bound internal promoters and PSE transcription factor-bound external promoters, respectively. The TFIIIB-alpha activity complex is composed of TBP, BDP1, and a complex containing both BRF2 and at least four stably associated proteins; YY1 facilitates the formation of TFIIIB-alpha activity complex. The TFIIIB-beta activity complex is composed of TBP, BDP1, and BRF1. Interacts with BRF1; this interaction diminishes during mitosis resulting in the release of BDP1 from chromosomal templates. Component of TFIIIC complex. The TFIIIC complex has two activities, C1 and C2. The TFIIIC2 activity complex is only required for transcription of the ‘classical’ pol III genes whereas the TFIIIC1 activity complex is required for transcription of all pol III genes. The TFIIIC1 activity complex is composed at least of BDP1. Interacts with ZBTB43.

Subcellular location. Nucleus.

Tissue specificity. Isoform 2 is highly expressed in cerebellum.

Post-translational modifications. Phosphorylated by CSNK2A1 during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription.

Disease relevance. Deafness, autosomal recessive, 112 (DFNB112) [MIM:618257] A form of non-syndromic, sensorineural deafness characterized by postlingual progressive hearing impairment. 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 may be caused by variants affecting the gene represented in this entry.

Induction. By Epstein-Barr virus (EBV) resulting in the stimulation of the EBV EBER genes.

Isoforms (8)

UniProt ID	Names	Canonical?
A6H8Y1-1	1	yes
A6H8Y1-2	2
A6H8Y1-3	3
A6H8Y1-4	4
A6H8Y1-5	5
A6H8Y1-6	6
A6H8Y1-7	7
A6H8Y1-8	8

RefSeq proteins (1): NP_060899* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR039467	TFIIIB_B’’_Myb	Domain

Pfam: PF15963

UniProt features (114 total): compositionally biased region 31, region of interest 20, splice variant 16, sequence variant 14, repeat 9, sequence conflict 8, mutagenesis site 5, helix 5, coiled-coil region 3, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
5N9G	X-RAY DIFFRACTION	2.7
9K3U	ELECTRON MICROSCOPY	3
9FSO	ELECTRON MICROSCOPY	3.28
9LXN	ELECTRON MICROSCOPY	3.3
9FSP	ELECTRON MICROSCOPY	3.39
8IUH	ELECTRON MICROSCOPY	3.4
9K3V	ELECTRON MICROSCOPY	3.5
9FSQ	ELECTRON MICROSCOPY	3.51
9FSR	ELECTRON MICROSCOPY	3.76
8ITY	ELECTRON MICROSCOPY	3.9
8IUE	ELECTRON MICROSCOPY	4.1
9FSS	ELECTRON MICROSCOPY	4.14
9K3B	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6H8Y1-F1	37.23	0.03

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 (1): 915

Mutagenesis-validated functional residues (5):

Position	Phenotype
446	not phosphorylated by csnk2a1; when associated with a-390; a-426; a-431 and a-437. ck2 treatment constitutively activate
390	not phosphorylated by csnk2a1; when associated with a-426; a-431; a-437 and a-446. ck2 treatment constitutively activate
426	not phosphorylated by csnk2a1; when associated with a-390; a-431; a-437 and a-446. ck2 treatment constitutively activate
431	not phosphorylated by csnk2a1; when associated with a-390; a-426; a-437 and a-446. ck2 treatment constitutively activate
437	not phosphorylated by csnk2a1; when associated with a-390; a-426; a-431 and a-446. ck2 treatment constitutively activate

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 129 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, SENESE_HDAC1_TARGETS_UP, RFX1_02, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, MARIADASON_REGULATED_BY_HISTONE_ACETYLATION_DN, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOMF_TRANSCRIPTION_FACTOR_BINDING, HAMAI_APOPTOSIS_VIA_TRAIL_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, GOBP_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_III_PROMOTER

GO Biological Process (1): RNA polymerase III preinitiation complex assembly (GO:0070898)

GO Molecular Function (2): TFIIIC-class transcription factor complex binding (GO:0001156), protein binding (GO:0005515)

GO Cellular Component (3): transcription factor TFIIIB complex (GO:0000126), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase III Transcription Initiation	3
RNA Polymerase III Transcription	2
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription initiation at RNA polymerase III promoter	1
transcription preinitiation complex assembly	1
RNA polymerase III general transcription initiation factor binding	1
binding	1
RNA polymerase III transcription regulator complex	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BDP1	GTF3C1	Q12789	998
BDP1	TBP	P20226	994
BDP1	BRF2	Q9HAW0	957
BDP1	MAF1	Q9H063	936
BDP1	GTF3A	Q92664	913
BDP1	POLR3A	O14802	902
BDP1	BRF1	Q92994	879
BDP1	NCOR1	O75376	862
BDP1	SMARCC1	Q92922	818
BDP1	POLI	Q9UNA4	818
BDP1	TP53	P04637	778
BDP1	POLR1D	P0DPB6	772
BDP1	UBTFL1	P0CB47	761
BDP1	POLR3C	Q9BUI4	748
BDP1	GTF2B	Q00403	746

IntAct

20 interactions, top by confidence:

A	B	Type	Score
BDP1	CALR	psi-mi:“MI:0915”(physical association)	0.400
BDP1	ERP29	psi-mi:“MI:0915”(physical association)	0.400
BDP1	SLC25A5	psi-mi:“MI:0915”(physical association)	0.400
BDP1	NPM1	psi-mi:“MI:0915”(physical association)	0.400
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
POLR1C	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR1D	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2E	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2H	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2K	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR3A	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR3B	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR3D	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR3E	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR3F	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR3H	BDP1	psi-mi:“MI:0914”(association)	0.350
TBP	BDP1	psi-mi:“MI:0914”(association)	0.350
BDP1		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (75): BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS), BDP1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM80, A6H8Y1, A7MBJ2, D3ZF42, E9Q6J5, F4I700, F4J3S1, F4KCE9, F6QRE9, O04251, O82345, P23497, P46100, P48785, P48786, Q04996, Q05B65, Q0WTB8, Q13342, Q15361, Q32MZ4, Q3UZ39, Q3ZBR9, Q4QSC8, Q571C7, Q5H9K5, Q5RHP9, Q61687, Q66HF9, Q7YQM3, Q7YQM4, Q7Z5L2, Q8BJM3, Q8C4A5, Q8C9B9, Q8GZ87, Q8H991, Q8IW19, Q92576, Q940Y3

Diamond homologs: A6H8Y1, O94481, P46678, Q571C7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ZBTB43	unknown	BDP1	binding
BDP1	“form complex”	TFIIIB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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
RNA Polymerase III Chain Elongation	12	447.8×	4e-31
RNA Polymerase III Transcription Termination	12	350.5×	2e-29
RNA Polymerase III Transcription Initiation From Type 2 Promoter	13	323.4×	4e-31
RNA Polymerase III Transcription Initiation From Type 1 Promoter	13	311.9×	4e-31
RNA Polymerase III Transcription Initiation From Type 3 Promoter	13	311.9×	4e-31
RNA Polymerase III Transcription Initiation	13	256.9×	7e-30
RNA Polymerase III Transcription	13	249.5×	9e-30
RNA Polymerase III Abortive And Retractive Initiation	13	213.0×	8e-29

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	5	212.8×	3e-09
defense response to virus	6	23.1×	4e-06
transcription by RNA polymerase II	5	19.6×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	319
Likely benign	144
Benign	133

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4687865	NM_018429.3(BDP1):c.5743del (p.Ser1915fs)	Likely pathogenic
4688031	NM_018429.3(BDP1):c.7254_7258delinsAATATCAT (p.Gly2419_Gln2420delinsIleSerTer)	Likely pathogenic
812719	NM_018429.3(BDP1):c.1714G>T (p.Val572Phe)	Likely pathogenic

SpliceAI

6246 predictions. Top by Δscore:

Variant	Effect	Δscore
5:71456088:AGGTA:A	donor_loss	1.0000
5:71456090:GTA:G	donor_loss	1.0000
5:71458568:A:AG	acceptor_gain	1.0000
5:71458569:A:G	acceptor_gain	1.0000
5:71458570:T:G	acceptor_gain	1.0000
5:71458574:A:AG	acceptor_gain	1.0000
5:71458575:A:G	acceptor_gain	1.0000
5:71458577:A:AG	acceptor_gain	1.0000
5:71458577:AG:A	acceptor_loss	1.0000
5:71458578:G:GC	acceptor_gain	1.0000
5:71458578:GT:G	acceptor_gain	1.0000
5:71458578:GTA:G	acceptor_gain	1.0000
5:71458578:GTAC:G	acceptor_gain	1.0000
5:71458578:GTACT:G	acceptor_gain	1.0000
5:71458680:T:G	donor_gain	1.0000
5:71464048:T:G	acceptor_gain	1.0000
5:71464048:T:TA	acceptor_gain	1.0000
5:71464053:A:AG	acceptor_gain	1.0000
5:71464054:ATAGT:A	acceptor_loss	1.0000
5:71464055:TA:T	acceptor_loss	1.0000
5:71464056:A:AG	acceptor_gain	1.0000
5:71464056:AGT:A	acceptor_loss	1.0000
5:71464057:G:A	acceptor_loss	1.0000
5:71464057:G:GC	acceptor_gain	1.0000
5:71464057:GT:G	acceptor_gain	1.0000
5:71464057:GTT:G	acceptor_gain	1.0000
5:71464057:GTTC:G	acceptor_gain	1.0000
5:71464057:GTTCT:G	acceptor_gain	1.0000
5:71464113:AGAGA:A	donor_gain	1.0000
5:71464114:GAGA:G	donor_gain	1.0000

AlphaMissense

17338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:71467475:T:A	W303R	1.000
5:71467475:T:C	W303R	1.000
5:71467477:G:C	W303C	1.000
5:71467477:G:T	W303C	1.000
5:71470407:T:C	F311S	1.000
5:71470416:C:A	A314D	1.000
5:71483848:T:C	F341L	1.000
5:71483849:T:C	F341S	1.000
5:71483850:T:A	F341L	1.000
5:71483850:T:G	F341L	1.000
5:71467448:T:C	F294L	0.999
5:71467449:T:C	F294S	0.999
5:71467450:T:A	F294L	0.999
5:71467450:T:G	F294L	0.999
5:71467476:G:C	W303S	0.999
5:71470406:T:C	F311L	0.999
5:71470408:T:A	F311L	0.999
5:71470408:T:G	F311L	0.999
5:71470409:T:C	F312L	0.999
5:71470411:T:A	F312L	0.999
5:71470411:T:G	F312L	0.999
5:71470415:G:C	A314P	0.999
5:71470419:T:A	I315N	0.999
5:71470430:G:A	G319R	0.999
5:71470430:G:C	G319R	0.999
5:71470431:G:A	G319E	0.999
5:71470431:G:T	G319V	0.999
5:71470437:A:G	D321G	0.999
5:71470437:A:T	D321V	0.999
5:71470439:T:C	F322L	0.999

dbSNP variants (sampled 300 via entrez): RS1000000381 (5:71514458 A>T), RS1000111280 (5:71570369 C>A), RS1000145817 (5:71540809 A>G,T), RS1000161827 (5:71505571 A>C), RS1000242248 (5:71479703 C>A,T), RS1000249211 (5:71570067 T>G), RS1000277739 (5:71485586 G>A), RS1000313240 (5:71523606 G>A), RS1000349853 (5:71472602 T>G), RS1000353549 (5:71468455 T>G), RS1000361109 (5:71537435 C>T), RS1000371497 (5:71466783 A>G), RS1000393842 (5:71560619 T>G), RS1000406324 (5:71554852 A>C), RS1000407371 (5:71468295 A>G)

Disease associations

OMIM: gene MIM:607012 | disease phenotypes: MIM:618257, MIM:193500, MIM:210210

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive	Supportive	Autosomal recessive
hearing loss, autosomal recessive 112	Limited	Autosomal recessive
nonsyndromic genetic hearing loss	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Limited	AR

Mondo (6): hearing loss, autosomal recessive 112 (MONDO:0032639), hearing loss disorder (MONDO:0005365), Waardenburg syndrome (MONDO:0018094), 3-methylcrotonyl-CoA carboxylase 2 deficiency (MONDO:0008862), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (2): Waardenburg syndrome (Orphanet:3440), 3-methylcrotonyl-CoA carboxylase deficiency (Orphanet:6)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0011463	Childhood onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_715	Obesity-related traits	9.000000e-06
GCST005174_18	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004723	coronary artery calcification

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
D014849	Waardenburg Syndrome	C16.131.077.938
C535309	3-methylcrotonyl CoA carboxylase 2 deficiency (supp.)
C564609	Deafness, Autosomal Recessive (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

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	decreases expression, decreases methylation	3
Tetrachlorodibenzodioxin	affects expression, affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Arsenic	affects methylation	1
Clorgyline	increases expression	1
Diuron	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	increases expression	1
Manganese	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases 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