SERPINB6

Summary

SERPINB6 (serpin family B member 6, HGNC:8950) is a protein-coding gene on chromosome 6p25.2, encoding Serpin B6 (P35237). May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood.

The protein encoded by this gene is a member of the serpin (serine proteinase inhibitor) superfamily, and ovalbumin(ov)-serpin subfamily. It was originally discovered as a placental thrombin inhibitor. The mouse homolog was found to be expressed in the hair cells of the inner ear. Mutations in this gene are associated with nonsyndromic progressive hearing loss, suggesting that this serpin plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5269 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive nonsyndromic hearing loss 91 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 217 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8950
Approved symbol	SERPINB6
Name	serpin family B member 6
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	PTI, CAP
Ensembl gene	ENSG00000124570
Ensembl biotype	protein_coding
OMIM	173321
Entrez	5269

Gene structure

Transcript identifiers

Ensembl transcripts: 94 — 88 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000380520, ENST00000380524, ENST00000380529, ENST00000380539, ENST00000380546, ENST00000612421, ENST00000616722, ENST00000642543, ENST00000643098, ENST00000643227, ENST00000643314, ENST00000644178, ENST00000644388, ENST00000644693, ENST00000644697, ENST00000644777, ENST00000644828, ENST00000644875, ENST00000645421, ENST00000645580, ENST00000646688, ENST00000646722, ENST00000646775, ENST00000647157, ENST00000649845, ENST00000860477, ENST00000860478, ENST00000860479, ENST00000860480, ENST00000860481, ENST00000860482, ENST00000860483, ENST00000860484, ENST00000860485, ENST00000860486, ENST00000860487, ENST00000860488, ENST00000860489, ENST00000860490, ENST00000860491, ENST00000860492, ENST00000860493, ENST00000860494, ENST00000860495, ENST00000860496, ENST00000860497, ENST00000860498, ENST00000860499, ENST00000860500, ENST00000860501, ENST00000860502, ENST00000860503, ENST00000860504, ENST00000860505, ENST00000860506, ENST00000860507, ENST00000860508, ENST00000860509, ENST00000860510, ENST00000860511, ENST00000860512, ENST00000860513, ENST00000860514, ENST00000860515, ENST00000922588, ENST00000922589, ENST00000922590, ENST00000950811, ENST00000950812, ENST00000950813, ENST00000950814, ENST00000950815, ENST00000950816, ENST00000950817, ENST00000950818, ENST00000950819, ENST00000950820, ENST00000950821, ENST00000950822, ENST00000950823, ENST00000950824, ENST00000950825, ENST00000950826, ENST00000950827, ENST00000950828, ENST00000950829, ENST00000950830, ENST00000950831, ENST00000950832, ENST00000950833, ENST00000950834, ENST00000950835, ENST00000950836, ENST00000950837

RefSeq mRNA: 11 — MANE Select: NM_004568 NM_001195291, NM_001271822, NM_001271823, NM_001271824, NM_001271825, NM_001297699, NM_001297700, NM_001374515, NM_001374516, NM_001374517, NM_004568

CCDS: CCDS4479, CCDS75386, CCDS75387, CCDS93850

Canonical transcript exons

ENST00000380539 — 7 exons

Exon	Start	End
ENSE00000680394	2954592	2954709
ENSE00000680395	2955524	2955670
ENSE00001365845	2953044	2953186
ENSE00001371369	2948914	2949069
ENSE00001961421	2959168	2959342
ENSE00003819926	2971533	2971567
ENSE00003899967	2948159	2948699

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.6658 / max 553.9949, expressed in 1798 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71433	24.1497	1786
71435	12.4775	1733
71438	6.6742	1674
71437	4.2916	1582
71436	2.5213	1372
71440	2.1477	1110
71439	1.6706	953
71441	1.2443	824
71434	0.6996	469
71428	0.6017	289

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.21	gold quality
left testis	UBERON:0004533	99.17	gold quality
right uterine tube	UBERON:0001302	99.03	gold quality
body of pancreas	UBERON:0001150	98.92	gold quality
apex of heart	UBERON:0002098	98.81	gold quality
left ovary	UBERON:0002119	98.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.57	gold quality
right atrium auricular region	UBERON:0006631	98.53	gold quality
right ovary	UBERON:0002118	98.48	gold quality
endocervix	UBERON:0000458	98.47	gold quality
right adrenal gland	UBERON:0001233	98.46	gold quality
right lung	UBERON:0002167	98.44	gold quality
right adrenal gland cortex	UBERON:0035827	98.44	gold quality
left adrenal gland cortex	UBERON:0035825	98.40	gold quality
heart left ventricle	UBERON:0002084	98.38	gold quality
lower esophagus mucosa	UBERON:0035834	98.38	gold quality
left adrenal gland	UBERON:0001234	98.37	gold quality
small intestine	UBERON:0002108	98.36	gold quality
left coronary artery	UBERON:0001626	98.32	gold quality
cardiac ventricle	UBERON:0002082	98.30	gold quality
upper lobe of left lung	UBERON:0008952	98.30	gold quality
right coronary artery	UBERON:0001625	98.28	gold quality
duodenum	UBERON:0002114	98.27	gold quality
cardiac atrium	UBERON:0002081	98.25	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.25	gold quality
coronary artery	UBERON:0001621	98.21	gold quality
adrenal cortex	UBERON:0001235	98.20	gold quality
gastrocnemius	UBERON:0001388	98.19	gold quality
lower esophagus	UBERON:0013473	98.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.15	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	66.94
E-MTAB-7303	yes	41.86
E-HCAD-1	yes	39.51
E-CURD-112	yes	33.81
E-GEOD-125970	yes	20.55
E-HCAD-9	yes	15.13
E-MTAB-9388	yes	11.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, IRF1, STAT3, STAT5B

miRNA regulators (miRDB)

8 targeting SERPINB6, 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-188-3P	100.00	68.76	1240
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• In mast cells, SERPINB6 serves to regulate the activity of endogenous beta-tryptase in the cytoplasm. (PMID:14670919)
• Expressed in developing gonads and in both somatic and germ cells of adult gonads. (PMID:16175637)
• Protects the intracellular compartment of keratinocytes from ectopic kallikrein-8. (PMID:17761692)
• the discovery overexpression of GPD1 and RRBP1 proteins and lack of expression for HNRNPH1 and SERPINB6 proteins which are new candidate biomarkers of colon cancer. (PMID:19425502)
• A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss. (PMID:20451170)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpinb6b	ENSMUSG00000042842
mus_musculus	Serpinb6d	ENSMUSG00000047889
mus_musculus	Serpinb6c	ENSMUSG00000052180
mus_musculus	Serpinb6a	ENSMUSG00000060147
mus_musculus	Serpinb6e	ENSMUSG00000069248
rattus_norvegicus	Serpinb6b	ENSRNOG00000016420
rattus_norvegicus	Serpinb6a	ENSRNOG00000017962
rattus_norvegicus	Serpinb6el1	ENSRNOG00000063990
rattus_norvegicus	Serpinb6e	ENSRNOG00000070025

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Serpin B6 — P35237 (reviewed: P35237)

Alternative names: Cytoplasmic antiproteinase, Peptidase inhibitor 6, Placental thrombin inhibitor

All UniProt accessions (12): A0A024QZX5, A0A087X1N8, A0A2R8Y517, A0A2R8Y5S1, A0A2R8Y5Y8, A0A2R8Y6A7, A0A2R8Y6N4, A0A2R8Y7E5, A0A2R8YD12, A0A2R8YDD0, A0A3B3ISC3, P35237

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood. Inhibitor of cathepsin G, kallikrein-8 and thrombin. May play an important role in the inner ear in the protection against leakage of lysosomal content during stress and loss of this protection results in cell death and sensorineural hearing loss.

Subunit / interactions. Forms a complex with the monomeric form of beta-tryptase.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in keratinocytes (at protein level). Highest levels in skeletal muscle. Also found in placenta, cardiac muscle, lung, liver, kidney and pancreas. Expressed in the inner ear hair cells. Expressed abundantly by normal mast cells in different tissues and by mast cells in mastocytoma lesions.

Disease relevance. Deafness, autosomal recessive, 91 (DFNB91) [MIM:613453] A form of non-syndromic deafness characterized by progressive and age-dependent sensorineural hearing loss. Vestibular function is normal. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the serpin family. Ov-serpin subfamily.

RefSeq proteins (11): NP_001182220, NP_001258751, NP_001258752, NP_001258753, NP_001258754, NP_001284628, NP_001284629, NP_001361444, NP_001361445, NP_001361446, NP_004559* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (10 total): modified residue 3, sequence conflict 3, sequence variant 2, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35237-F1	91.25	0.81

Functional residue map

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

Catalytic / active sites (1): 341–342 (reactive bond)

Post-translational modifications (3): 1, 151, 195

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-109582	Hemostasis
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 228 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, HSIAO_HOUSEKEEPING_GENES, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, KYNG_DNA_DAMAGE_DN, GOLDRATH_ANTIGEN_RESPONSE, chr6p25, SMITH_TERT_TARGETS_DN, BORLAK_LIVER_CANCER_EGF_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (2): sensory perception of sound (GO:0007605), cellular response to osmotic stress (GO:0071470)

GO Molecular Function (3): protease binding (GO:0002020), serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), secretory granule membrane (GO:0030667), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), serine protease inhibitor complex (GO:0097180), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	1
Hemostasis	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
secretory granule membrane	2
tertiary granule	2
sensory perception of mechanical stimulus	1
response to osmotic stress	1
cellular response to chemical stress	1
cellular response to abiotic stimulus	1
enzyme binding	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
external encapsulating structure	1
extracellular vesicle	1
protease inhibitor complex	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINB6	SPI1	P17947	647
SERPINB6	GZMB	P10144	521
SERPINB6	GIPC3	Q8TF64	506
SERPINB6	GRXCR1	A8MXD5	480
SERPINB6	TPRN	Q4KMQ1	479
SERPINB6	PI3	P19957	464
SERPINB6	SPINK9	Q5DT21	456
SERPINB6	TMPRSS3	P57727	450
SERPINB6	TMIE	Q8NEW7	447
SERPINB6	SERPINB2	P05120	422
SERPINB6	OTOA	Q7RTW8	419
SERPINB6	TMC1	Q8TDI8	419
SERPINB6	MYO3A	Q8NEV4	415
SERPINB6	BPIFB1	Q8TDL5	408
SERPINB6	PJVK	Q0ZLH3	400

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CEP170P1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
PCNA	SERPINB6	psi-mi:“MI:0915”(physical association)	0.370
SERPINB6	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
SERPINB6	PLAT	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
rep	PRDX5	psi-mi:“MI:0914”(association)	0.350
KLK13	SERPINE2	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
HK1	DVL2	psi-mi:“MI:0914”(association)	0.350
NME3	VWA8	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
USP46	UBA6	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
	MYO1C	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
LARP7	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (60): SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS), ITPA (Co-fractionation), XYLB (Co-fractionation), SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), PLAT (Affinity Capture-MS), SERPINB6 (Affinity Capture-RNA), SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS), SERPINB6 (Affinity Capture-MS)

ESM2 similar proteins: O00394, O02739, O08800, O54757, O54758, O54759, O54760, O54761, O54762, O54763, P01009, P01010, P05619, P07758, P12725, P17475, P22324, P22325, P22599, P23035, P29508, P30740, P34955, P35237, P38029, P48594, P50447, P50452, P50453, P80229, P97277, Q00896, Q00897, Q00898, Q09055, Q1JPB0, Q4G075, Q4R3G2, Q52L45, Q5BIR5

Diamond homologs: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A5PJK0, A9RA96, B0CMB0, B1MTB7, B1MTC3, B2KI30, B3RFC3, B4USX2, E2RVI8, O02739, O08800, O35684, O54757, O54758, O54759, O54760, O73790, O73860, O75635, O75830, P01008, P01011, P01012, P01014, P05120, P05619, P12388, P17475, P19104, P22323, P22325, P22922, P23035, P29508, P29524, P30740

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	87
Likely benign	63
Benign	36

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
13601	NM_004568.6(SERPINB6):c.733G>T (p.Glu245Ter)	Pathogenic
1325052	NM_004568.6(SERPINB6):c.3G>C (p.Met1Ile)	Likely pathogenic
3338321	NM_004568.6(SERPINB6):c.217C>T (p.Gln73Ter)	Likely pathogenic
506010	NM_004568.6(SERPINB6):c.679G>T (p.Glu227Ter)	Likely pathogenic

SpliceAI

1392 predictions. Top by Δscore:

Variant	Effect	Δscore
6:2948899:CAG:C	donor_gain	1.0000
6:2948906:G:C	donor_gain	1.0000
6:2955518:ACTT:A	donor_loss	1.0000
6:2955521:TACTG:T	donor_loss	1.0000
6:2955522:A:AC	donor_gain	1.0000
6:2955522:ACTGA:A	donor_loss	1.0000
6:2955523:C:A	donor_loss	1.0000
6:2955523:C:CA	donor_gain	1.0000
6:2955523:CT:C	donor_gain	1.0000
6:2955523:CTG:C	donor_gain	1.0000
6:2955523:CTGA:C	donor_gain	1.0000
6:2955523:CTGAG:C	donor_gain	1.0000
6:2955568:T:TA	donor_gain	1.0000
6:2955666:AGTAT:A	acceptor_gain	1.0000
6:2955667:GTAT:G	acceptor_gain	1.0000
6:2955668:TAT:T	acceptor_gain	1.0000
6:2955669:ATCTG:A	acceptor_loss	1.0000
6:2955670:TCTGA:T	acceptor_loss	1.0000
6:2955671:C:CC	acceptor_gain	1.0000
6:2955671:C:G	acceptor_loss	1.0000
6:2955672:T:A	acceptor_loss	1.0000
6:2955678:C:CT	acceptor_gain	1.0000
6:2948697:CACCT:C	acceptor_loss	0.9900
6:2948698:ACCTA:A	acceptor_loss	0.9900
6:2948699:CCT:C	acceptor_loss	0.9900
6:2948700:C:G	acceptor_loss	0.9900
6:2948701:T:C	acceptor_loss	0.9900
6:2948913:CCGTT:C	donor_gain	0.9900
6:2949066:CATT:C	acceptor_gain	0.9900
6:2949067:ATT:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002890 (6:2965182 T>C), RS1000064777 (6:2972437 G>A,C), RS1000089540 (6:2963711 T>C), RS1000153787 (6:2955349 T>C,G), RS1000295814 (6:2966257 G>C,T), RS1000296560 (6:2960278 A>G), RS1000386687 (6:2961337 T>C), RS1000514405 (6:2966794 T>C), RS1000545422 (6:2967299 G>A,T), RS1000632354 (6:2961625 T>C), RS1000645165 (6:2950292 G>A), RS1000725437 (6:2962015 G>A), RS1000830914 (6:2956245 T>C), RS1000891817 (6:2954960 C>T), RS1000895100 (6:2967824 G>A)

Disease associations

OMIM: gene MIM:173321 | disease phenotypes: MIM:613453, MIM:276900

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive nonsyndromic hearing loss 91	Definitive	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Moderate	AR

Mondo (4): hearing loss disorder (MONDO:0005365), autosomal recessive nonsyndromic hearing loss 91 (MONDO:0013269), Usher syndrome (MONDO:0019501), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (3): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Usher syndrome (Orphanet:886), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001730	Progressive hearing impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003468_21	Chronic lymphocytic leukemia	2.000000e-08
GCST010577_24	Crohn’s disease	4.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C564609	Deafness, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066433 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.26	Kd	55.14	nM	CHEMBL5653589
7.26	ED50	55.14	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149379: Binding affinity to human SERPINB6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0551	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, decreases expression, affects cotreatment	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-hydroxy-equilenin	decreases expression	1
K 7174	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
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652421	Binding	Binding affinity to human SERPINB6 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

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