KLK6

Summary

KLK6 (kallikrein related peptidase 6, HGNC:6367) is a protein-coding gene on chromosome 19q13.41, encoding Kallikrein-6 (Q92876). Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position.

This gene encodes a member of the kallikrein subfamily of the peptidase S1 family of serine proteases. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. The encoded preproprotein is proteolytically processed to generate the mature protease. Expression of this protease is regulated by steroid hormones and may be elevated in multiple human cancers and in serum from psoriasis patients. The encoded protease may participate in the cleavage of amyloid precursor protein and alpha-synuclein, thus implicating this protease in Alzheimer’s and Parkinson’s disease, respectively. This gene is located in a gene cluster on chromosome 19. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5653 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 94 total
• Druggable target: yes
• MANE Select transcript: NM_002774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6367
Approved symbol	KLK6
Name	kallikrein related peptidase 6
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	Bssp, Klk7, neurosin
Ensembl gene	ENSG00000167755
Ensembl biotype	protein_coding
OMIM	602652
Entrez	5653

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 nonsense_mediated_decay

ENST00000310157, ENST00000376851, ENST00000391808, ENST00000594641, ENST00000597379, ENST00000599690, ENST00000599881, ENST00000971784

RefSeq mRNA: 5 — MANE Select: NM_002774 NM_001012964, NM_001012965, NM_001319948, NM_001319949, NM_002774

CCDS: CCDS12811, CCDS42599

Canonical transcript exons

ENST00000310157 — 7 exons

Exon	Start	End
ENSE00001188283	50968541	50968591
ENSE00002247472	50968065	50968112
ENSE00003139628	50958631	50959316
ENSE00003506174	50963302	50963549
ENSE00003534932	50961744	50961880
ENSE00003559289	50967169	50967325
ENSE00003846718	50969490	50969591

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 99.38.

FANTOM5 (CAGE): breadth broad, TPM avg 12.7336 / max 1819.5843, expressed in 436 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182312	5.3910	142
182304	2.9591	243
182311	2.9141	191
182302	0.3790	123
182305	0.2212	50
182299	0.2131	47
182303	0.2026	50
182307	0.1715	52
182306	0.1093	31
182309	0.0993	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.38	gold quality
spinal cord	UBERON:0002240	99.03	gold quality
inferior vagus X ganglion	UBERON:0005363	98.21	gold quality
inferior olivary complex	UBERON:0002127	97.42	gold quality
middle frontal gyrus	UBERON:0002702	96.87	gold quality
pons	UBERON:0000988	96.29	gold quality
corpus callosum	UBERON:0002336	96.02	gold quality
cranial nerve II	UBERON:0000941	95.67	gold quality
subthalamic nucleus	UBERON:0001906	95.62	gold quality
medulla oblongata	UBERON:0001896	95.50	gold quality
substantia nigra	UBERON:0002038	95.47	gold quality
midbrain	UBERON:0001891	95.38	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.77	gold quality
superior vestibular nucleus	UBERON:0007227	93.67	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.33	gold quality
ventral tegmental area	UBERON:0002691	93.28	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.17	gold quality
lateral globus pallidus	UBERON:0002476	91.84	gold quality
substantia nigra pars compacta	UBERON:0001965	91.45	gold quality
globus pallidus	UBERON:0001875	91.32	gold quality
pharyngeal mucosa	UBERON:0000355	91.05	gold quality
putamen	UBERON:0001874	90.99	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.86	gold quality
medial globus pallidus	UBERON:0002477	90.77	gold quality
Ammon’s horn	UBERON:0001954	90.66	gold quality
renal glomerulus	UBERON:0000074	90.05	gold quality
hypothalamus	UBERON:0001898	89.86	gold quality
metanephric glomerulus	UBERON:0004736	89.77	gold quality
amygdala	UBERON:0001876	89.20	gold quality
mammalian vulva	UBERON:0000997	88.22	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	850.75
E-GEOD-124472	yes	566.78
E-HCAD-10	yes	23.28
E-MTAB-8410	yes	21.73
E-GEOD-84465	yes	11.75
E-ANND-3	yes	4.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting KLK6, 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-4500	99.99	72.72	2367
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-630	97.50	66.38	921
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-4758-5P	94.82	67.06	499
HSA-MIR-6753-5P	94.70	64.08	470

Literature-anchored findings (GeneRIF, showing 40)

• characterization of human kallikrein 6 as a degradative protease with structural features more similar to trypsin than the regulatory kallikreins (PMID:11983703)
• X-ray crystallographic structure of KLK6. (PMID:12016211)
• Kallikrein 6, a myelencephalon-specific protease expressed in the adult central nervous system (CNS), is present in inflammatory CNS lesions (e.g., multiple sclerosis) and in excess promotes CNS demyelination. (PMID:12023317)
• Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer’s disease patients (PMID:12074831)
• Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker. (PMID:12232761)
• Decreased cerebrospinal fluid levels may be a posssible risk factor for Alzheimer’s disease (PMID:12480753)
• Characterization of the enzymatic activity of kallikrein 6. (PMID:12878203)
• neurosin plays a significant role in physiological alpha-synuclein degradation and also in the pathogenesis of synucleinopathies (PMID:12928483)
• Downregulation of kallikrein 6 is associated with breast cancer (PMID:14696124)
• Distinct promoters regulate tissue-specific expression of KLK6 gene. Cloning of three novel transcript variants of KLK6 gene that encode for wild-type kallikrein 6 and of splice variants 2 and 3 produced by splicing out exons 3 and 4, respectively. (PMID:15207701)
• The enzymatic activity of hK6 is regulated by an autoactivation/autoinactivation mechanism. Mature hK6 displayed a trypsin-like activity against synthetic substrates and human plasminogen was identified as a putative physiological substrate for hK6 (PMID:15255184)
• Human KLK6 might play a role in the invasion and metastasis of tumour cells and may be a candidate therapeutic target. (PMID:15557757)
• Tissue-specific expression patterns and differential regulation in CNS disease indicates that each K6 5’-transcript is probably regulated by unique promoter elements and may serve as a molecular target to treat inflammatory demyelinating disease. (PMID:15584920)
• Results indicated that KLK6 mRNA expression was significantly higher in cancerous than in noncancerous colorectal tissues. (PMID:15837738)
• Kallikrein 6 is highly expressed in uterine serous papillary carcinoma (USPC) and is released in the plasma and serum and may represent a novel biomarker for USPC for monitoring early disease recurrence and response to therapy. (PMID:15867230)
• KLK6 is markedly overexpressed in gastric cancer tissue (PMID:16203767)
• hK6 expressed in the central nervous system is involved in normal myelin turnover/demyelination processes, but it is unlikely to self-activate (PMID:16321973)
• KLK6 may participate in epidermal desquamation through cleavage of desmoglein 1 and regulation by lympho-epithelial Kazal-type-related inhibitor (LEKTI). (PMID:17158887)
• KLK6 displayed trypsin-like activity, with the P1 position occupied only by Arg and a strong preference for Ser in P1’. (PMID:18359858)
• the oncogenic role of KLK6 in colorectal cancer (PMID:18627290)
• Co-expression of KLK6 and KLK10 as prognostic factors for survival in pancreatic ductal adenocarcinoma. (PMID:18854834)
• High tumor KLK6 protein expression is associated with inferior patient outcome in ovarian cancer. (PMID:18957059)
• KLK6 expression in cancerous tissues may play an important role in the invasion and metastasis of primary breast carcinoma. (PMID:18992199)
• The aim of this study was to characterize and compare the N-glycosylation status of Kallikrein 6 in ovarian cancer ascites fluid and cerebrospinal fluid. (PMID:19088065)
• KLK6 may play a protective role against tumor progression that is likely mediated by inhibition of epithelial-to-mesenchymal transition. KLK6 may be an epigenetically regulated tumor suppressor in human breast cancer (PMID:19383923)
• KLK6 has a role in tumour proliferation and progression of NSCLC (PMID:19426157)
• Combination of KLK2, 3, 13, and 14 and KLK1, 2, 5, 6, 7, 8, 10, 13, and 14 showed very strong discriminatory potential for semen liquefaction and viscosity, respectively. (PMID:19558318)
• Data show that it was unable to distinguish men with and without prostate cancer using multiple kallikreins as urinary biomarkers. (PMID:19560453)
• KLK6 and KLK13 predict tumor recurrence in epithelial ovarian carcinoma. (PMID:19707197)
• The expression of hK6 in ovarian cancer was higher than that in benign and borderline ovarian neoplasms. Expression is higher in the ovarian cancer of late stage, higher-grade, with lymph node metastasis and is associated with a poorer prognosis. (PMID:19950700)
• Neurosin targets extracellular alpha-synuclein in cultured cells. (PMID:20403393)
• upregulated in late stage epithelial ovarian cancer (PMID:20680316)
• Patients diagnosed with advanced multiple sclerosis showed mean CSF levels of kallikrein-related peptidase 6 (29 ng/ml) that were significantly higher than in neurological controls (25.5 ng/ml). (PMID:20836755)
• an altered KLK6 expression may contribute to vascular abnormalities in Alzheimer’s disease and vascular dementia (PMID:20846516)
• The expression of kallikrein 7 and kallikrein 6 in melanomas may be responsible for the loss of cell-cell adhesion. (PMID:21193224)
• KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of PAR1. (PMID:21464892)
• KLK6 was up-regulated significantly in tissues and sera from patients with colon cancer and was associated closely with a poor prognosis. (PMID:21656738)
• Data indicate there was no SNP in KLK6 was associated with altered risk of prostate cancer. (PMID:21741862)
• KLK6-induced intracellular Ca(2+) flux and tumor cell invasion critically depends on the protease-activated receptor 1 (PAR1). (PMID:21753781)
• High KLK6 is associated with ovarian cancer. (PMID:22102857)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klk6	ENSMUSG00000050063
rattus_norvegicus	Klk6	ENSRNOG00000031927

Paralogs (6): CMA1 (ENSG00000092009), CTSG (ENSG00000100448), GZMH (ENSG00000100450), GZMB (ENSG00000100453), KLK13 (ENSG00000167759), AZU1 (ENSG00000172232)

Protein

Protein identifiers

Kallikrein-6 — Q92876 (reviewed: Q92876)

Alternative names: Neurosin, Protease M, SP59, Serine protease 18, Serine protease 9, Zyme

All UniProt accessions (2): Q92876, M0QYA5

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Degrades alpha-synuclein and prevents its polymerization, indicating that it may be involved in the pathogenesis of Parkinson disease and other synucleinopathies. May be involved in regulation of axon outgrowth following spinal cord injury. Tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion and metastasis.

Subcellular location. Secreted. Nucleus. Nucleolus. Cytoplasm. Mitochondrion. Microsome.

Tissue specificity. In fluids, highest levels found in milk of lactating women followed by cerebrospinal fluid, nipple aspirate fluid and breast cyst fluid. Also found in serum, seminal plasma and some amniotic fluids and breast tumor cytosolic extracts. Not detected in urine. At the tissue level, highest concentrations found in glandular tissues such as salivary glands followed by lung, colon, fallopian tube, placenta, breast, pituitary and kidney. Not detected in skin, spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium, testis, pancreas, seminal vesicle, ovary, adrenals and prostate. In brain, detected in gray matter neurons (at protein level). Colocalizes with pathological inclusions such as Lewy bodies and glial cytoplasmic inclusions. Overexpressed in primary breast tumors but not expressed in metastatic tumors.

Post-translational modifications. Inactivated by autolytic cleavage after Arg-80.

Activity regulation. Inhibited by a range of serine protease inhibitors including soybean trypsin inhibitor, benzamidine and serpins. Activated by a range of glycosaminoglycans including chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin.

Induction. By spinal cord injury. This effect is particularly prominent in macrophages, microglia and reactive astrocytes.

Similarity. Belongs to the peptidase S1 family. Kallikrein subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92876-1	1	yes
Q92876-2	2
Q92876-3	3

RefSeq proteins (5): NP_001012982, NP_001012983, NP_001306877, NP_001306878, NP_002765* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.104 — mannan-binding lectin-associated serine protease-2 (BRENDA: 5 organisms, 101 substrates, 31 inhibitors, 26 Km, 27 kcat entries)
• EC 3.4.21.34 — plasma kallikrein (BRENDA: 20 organisms, 187 substrates, 209 inhibitors, 33 Km, 24 kcat entries)
• EC 3.4.21.B10 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

43 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
COMPLEMENT COMPONENT C4	0.0001–74	8
COMPLEMENT COMPONENT C2	0.0052–6.5	5
D-BUTYL-CYCLOHEXYLALANINE-ARGININE-4-NITROANILID	0.091–0.117	3
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.0136–0.0962	2
NALPHA-TOLUENESULFONYL-L-ARGININE METHYL ESTER	0.0016–0.136	2
C1-INHIBITOR P4-P1 FRAGMENT	0.123	1
C1-INHIBITOR P4-P4’ FRAGMENT	0.123	1
COMPLEMENT COMPONENT C2 P4-P1 FRAGMENT	0.015	1
COMPLEMENT COMPONENT C2 P4-P4’ FRAGMENT	0.173	1
COMPLEMENT COMPONENT C4 P4-P1 FRAGMENT	0.0155	1
COMPLEMENT COMPONENT C4 P4-P4’ FRAGMENT	0.271	1
N-ACETYLGLYCINE-L-LYSINE METHYL ESTER	6.7	1
N-CARBOXYBENZOYLGLYCINE-L-ARGININE THIOBENZYL ES	40	1
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER	4.4	1
P-TOSYL-L-ARGININE METHYL ESTER	2.8	1

UniProt features (45 total): strand 17, disulfide bond 6, helix 5, turn 4, splice variant 3, active site 3, signal peptide 1, propeptide 1, sequence variant 1, chain 1, domain 1, site 1, glycosylation site 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
7QFT	X-RAY DIFFRACTION	1.47
7QHZ	X-RAY DIFFRACTION	1.5
1LO6	X-RAY DIFFRACTION	1.56
7QFV	X-RAY DIFFRACTION	1.56
6QFF	X-RAY DIFFRACTION	1.64
6QFH	X-RAY DIFFRACTION	1.65
4D8N	X-RAY DIFFRACTION	1.68
6QFG	X-RAY DIFFRACTION	1.68
1L2E	X-RAY DIFFRACTION	1.75
1GVL	X-RAY DIFFRACTION	1.8
6QHA	X-RAY DIFFRACTION	1.82
6QHB	X-RAY DIFFRACTION	1.84
6SKB	X-RAY DIFFRACTION	1.84
5NX1	X-RAY DIFFRACTION	1.85
6QHC	X-RAY DIFFRACTION	1.87
3VFE	X-RAY DIFFRACTION	1.88
7QI0	X-RAY DIFFRACTION	1.88
6SKC	X-RAY DIFFRACTION	2.18
6SKD	X-RAY DIFFRACTION	2.26
6QH9	X-RAY DIFFRACTION	2.27
5NX3	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92876-F1	91.72	0.87

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 (4): 62 (charge relay system); 106 (charge relay system); 197 (charge relay system); 80–81 (cleavage; by autolysis)

Disulfide bonds (6): 47–63, 131–231, 138–203, 168–182, 193–218, 28–157

Glycosylation sites (1): 134

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 236 (showing top): MODULE_172, RNGTGGGC_UNKNOWN, WANG_CLIM2_TARGETS_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOMF_METALLOPEPTIDASE_ACTIVITY, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_REGENERATION, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_NEUROGENESIS

GO Biological Process (13): central nervous system development (GO:0007417), response to wounding (GO:0009611), regulation of neuron projection development (GO:0010975), protein autoprocessing (GO:0016540), collagen catabolic process (GO:0030574), tissue regeneration (GO:0042246), hormone metabolic process (GO:0042445), myelination (GO:0042552), amyloid precursor protein metabolic process (GO:0042982), regulation of cell differentiation (GO:0045595), positive regulation of G protein-coupled receptor signaling pathway (GO:0045745), protein maturation (GO:0051604), proteolysis (GO:0006508)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (12): cornified envelope (GO:0001533), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), secretory granule (GO:0030141), nuclear membrane (GO:0031965), intercellular bridge (GO:0045171), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein metabolic process	3
intracellular membrane-bounded organelle	3
nuclear lumen	2
cytoplasm	2
endomembrane system	2
nervous system development	1
system development	1
response to stress	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
protein processing	1
catabolic process	1
collagen metabolic process	1
regeneration	1
developmental growth	1
metabolic process	1
regulation of hormone levels	1
axon ensheathment	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
G protein-coupled receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
positive regulation of signal transduction	1
gene expression	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
plasma membrane	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
secretory vesicle	1
nucleus	1
nuclear envelope	1

Protein interactions and networks

STRING

1706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLK6	A2ML1	A8K2U0	738
KLK6	CDSN	Q15517	735
KLK6	SPINK5	Q9NQ38	698
KLK6	SPRR1B	P22528	693
KLK6	YAF2	Q8IY57	662
KLK6	GLIS1	Q8NBF1	614
KLK6	SNCA	P37840	604
KLK6	TGM1	P22735	598
KLK6	IVL	P07476	585
KLK6	GABPB1	Q06547	556
KLK6	DSG1	Q02413	543
KLK6	KRT10	P13645	512
KLK6	OPALIN	Q96PE5	507
KLK6	DSC1	Q08554	493
KLK6	SERPINB13	Q9UIV8	485

IntAct

547 interactions, top by confidence:

A	B	Type	Score
KLK6	ACP2	psi-mi:“MI:0915”(physical association)	0.560
ASPH	KLK6	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	KLK6	psi-mi:“MI:0915”(physical association)	0.560
PTTG1IP	KLK6	psi-mi:“MI:0915”(physical association)	0.560
KLK6	CDH16	psi-mi:“MI:0915”(physical association)	0.560
CDK8	KLK6	psi-mi:“MI:0915”(physical association)	0.560
KLK6	CFL2	psi-mi:“MI:0915”(physical association)	0.560
KLK6	COL9A1	psi-mi:“MI:0915”(physical association)	0.560
COX4I1	KLK6	psi-mi:“MI:0915”(physical association)	0.560
KLK6	CSNK2A1	psi-mi:“MI:0915”(physical association)	0.560
CTSH	KLK6	psi-mi:“MI:0915”(physical association)	0.560
KLK6		psi-mi:“MI:0915”(physical association)	0.560
KLK6	DBH	psi-mi:“MI:0915”(physical association)	0.560
KLK6	GADD45A	psi-mi:“MI:0915”(physical association)	0.560
EIF4B	KLK6	psi-mi:“MI:0915”(physical association)	0.560
KLK6	EPB42	psi-mi:“MI:0915”(physical association)	0.560
KLK6	FAU	psi-mi:“MI:0915”(physical association)	0.560
KLK6	GATA1	psi-mi:“MI:0915”(physical association)	0.560
KLK6	HK3	psi-mi:“MI:0915”(physical association)	0.560
KLK6	HOXB1	psi-mi:“MI:0915”(physical association)	0.560
KLK6	IL16	psi-mi:“MI:0915”(physical association)	0.560
KLK6	KRT19	psi-mi:“MI:0915”(physical association)	0.560
KLK6	KRT81	psi-mi:“MI:0915”(physical association)	0.560
LASP1	KLK6	psi-mi:“MI:0915”(physical association)	0.560
LMX1A	KLK6	psi-mi:“MI:0915”(physical association)	0.560
SMAD5	KLK6	psi-mi:“MI:0915”(physical association)	0.560
MATK	KLK6	psi-mi:“MI:0915”(physical association)	0.560
KLK6	MAP3K5	psi-mi:“MI:0915”(physical association)	0.560
	KLK6	psi-mi:“MI:0915”(physical association)	0.560
NEUROG1	KLK6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (31): KLK6 (Two-hybrid), KLK6 (Two-hybrid), KLK6 (Two-hybrid), KLK6 (Two-hybrid), KLK6 (Affinity Capture-MS), KLK6 (Affinity Capture-MS), KLK6 (Affinity Capture-MS), CDYL (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), KLK6 (Affinity Capture-MS), KLK6 (Affinity Capture-MS), KLK6 (Affinity Capture-MS), CDYL (Affinity Capture-MS)

ESM2 similar proteins: A7WPL7, O35164, O35205, O46683, O88780, P00770, P04187, P07288, P08883, P08884, P09582, P09650, P10144, P11032, P11034, P13366, P15119, P17977, P20151, P20718, P21812, P21842, P21844, P23946, P28293, P33619, P36368, P36369, P43430, P49862, P50339, P50340, P50341, P52195, P56435, P79204, P80219, P80931, P85202, P97592

Diamond homologs: A4D1T9, O35205, P00760, P00761, P00762, P00763, P00764, P06868, P06871, P06872, P07146, P07477, P07478, P08426, P12788, P16049, P19799, P32821, P32822, P35030, P35031, P35032, P35033, P70059, Q29463, Q32KU2, Q32LI2, Q4R7Y7, Q5K2P8, Q5K2P9, Q5K4E3, Q5M8S2, Q6IE06, Q7JIG6, Q8BW11, Q8IYP2, Q8NHM4, Q90627, Q90628, Q90629

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 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
Anchoring fibril formation	8	56.4×	9e-11
Crosslinking of collagen fibrils	9	47.6×	4e-11
Fibronectin matrix formation	8	42.3×	1e-09
Attachment of bacteria to epithelial cells	6	27.6×	3e-06
Collagen chain trimerization	9	21.6×	3e-08
Laminin interactions	6	21.1×	2e-05
Assembly of collagen fibrils and other multimeric structures	10	18.6×	2e-08
Collagen degradation	10	16.3×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	9	13.6×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

793 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50979786:A:AC	donor_gain	1.0000
19:50979787:C:CC	donor_gain	1.0000
19:50979787:CATTG:C	donor_gain	1.0000
19:50979921:GTCA:G	acceptor_gain	1.0000
19:50979925:C:CC	acceptor_gain	1.0000
19:50979782:TCTCA:T	donor_loss	0.9900
19:50979783:CTCAC:C	donor_loss	0.9900
19:50979784:TCA:T	donor_loss	0.9900
19:50979785:CA:C	donor_loss	0.9900
19:50979787:C:CG	donor_loss	0.9900
19:50979787:CA:C	donor_gain	0.9900
19:50979853:TGTAA:T	donor_gain	0.9900
19:50979920:GGTCA:G	acceptor_gain	0.9900
19:50979922:TCA:T	acceptor_gain	0.9900
19:50979923:CA:C	acceptor_gain	0.9900
19:50979923:CAC:C	acceptor_gain	0.9900
19:50979924:ACT:A	acceptor_loss	0.9900
19:50979925:C:T	acceptor_loss	0.9900
19:50979926:T:A	acceptor_loss	0.9900
19:50982165:C:CA	donor_gain	0.9900
19:50982309:T:TA	donor_gain	0.9900
19:50982310:C:A	donor_gain	0.9900
19:50977690:CC:C	acceptor_gain	0.9800
19:50977691:CC:C	acceptor_gain	0.9800
19:50979781:GTCTC:G	donor_loss	0.9800
19:50979928:C:CT	acceptor_gain	0.9800
19:50977688:CACC:C	acceptor_gain	0.9700
19:50979929:A:T	acceptor_gain	0.9700
19:50980484:CTCA:C	acceptor_gain	0.9700
19:50981765:A:AC	donor_gain	0.9700

AlphaMissense

1592 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50963318:C:A	W143C	0.999
19:50963318:C:G	W143C	0.999
19:50959191:C:A	W236C	0.998
19:50959191:C:G	W236C	0.998
19:50961781:C:G	C182S	0.998
19:50961782:A:T	C182S	0.998
19:50963430:T:A	D106V	0.998
19:50963430:T:G	D106A	0.998
19:50963431:C:G	D106H	0.998
19:50959260:C:A	W213C	0.997
19:50959260:C:G	W213C	0.997
19:50967178:C:G	C63S	0.997
19:50967179:A:T	C63S	0.997
19:50959312:T:A	D196V	0.996
19:50961748:C:G	C193S	0.996
19:50961749:A:T	C193S	0.996
19:50961823:C:G	C168S	0.996
19:50961824:A:T	C168S	0.996
19:50967178:C:T	C63Y	0.996
19:50959307:C:A	G198W	0.995
19:50959312:T:G	D196A	0.995
19:50963317:C:A	G144C	0.995
19:50963320:A:G	W143R	0.995
19:50963320:A:T	W143R	0.995
19:50963429:G:C	D106E	0.995
19:50963429:G:T	D106E	0.995
19:50959306:C:A	G198V	0.994
19:50959313:C:G	D196H	0.994
19:50961781:C:T	C182Y	0.994
19:50961782:A:G	C182R	0.994

dbSNP variants (sampled 300 via entrez): RS1000013970 (19:50970025 C>T), RS1000128279 (19:50969743 G>A), RS1000170864 (19:50966301 C>T), RS1000240047 (19:50965053 T>A), RS1000361952 (19:50959748 A>C,G), RS1000686919 (19:50960354 G>C), RS1000736569 (19:50960512 G>A,C), RS1001017683 (19:50971179 G>A), RS1001176695 (19:50967524 C>G), RS1001371091 (19:50967243 G>A), RS1001406190 (19:50965626 G>T), RS1001529702 (19:50970550 G>A), RS1002168683 (19:50960970 C>T), RS1002480280 (19:50971350 G>A,T), RS1002534369 (19:50971550 C>A,T)

Disease associations

OMIM: gene MIM:602652 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_559	Blood protein levels	4.000000e-24
GCST011743_28	HDL cholesterol levels in HIV infection	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4448 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 32 [PMID: 31675166]	Inhibition	8.6	pIC50
DKFZ‐251	Inhibition	6.89	pIC50
compound 5 {PMID: 24900446]	Inhibition	5.82	pIC50

ChEMBL bioactivities

65 potent at pChembl≥5 of 75 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	IC50	2.512	nM	CHEMBL4210711
7.75	IC50	18	nM	CHEMBL4217078
7.64	IC50	23	nM	CHEMBL4206734
7.00	IC50	100	nM	CHEMBL4216138
7.00	IC50	100	nM	CHEMBL4212718
6.89	IC50	130	nM	CHEMBL4210314
6.89	IC50	130	nM	CHEMBL4218203
6.82	IC50	150	nM	CHEMBL4203947
6.72	IC50	190	nM	CHEMBL4211164
6.60	IC50	250	nM	CHEMBL4207925
6.60	IC50	250	nM	CHEMBL4214705
6.54	IC50	290	nM	CHEMBL4218314
6.33	IC50	470	nM	CHEMBL4218203
6.31	IC50	490	nM	CHEMBL4211677
6.19	IC50	640	nM	CHEMBL4212332
6.10	Ki	800	nM	CHEMBL4861066
6.10	Ki	790	nM	CHEMBL5028148
6.05	IC50	890	nM	CHEMBL4208878
6.00	Ki	1000	nM	CHEMBL4862261
6.00	Ki	1000	nM	CHEMBL5028737
5.93	IC50	1170	nM	CHEMBL5028148
5.92	IC50	1200	nM	CHEMBL4204137
5.92	IC50	1200	nM	CHEMBL4218619
5.91	IC50	1230	nM	CHEMBL5028148
5.85	IC50	1400	nM	CHEMBL4215806
5.82	IC50	1500	nM	CHEMBL2047313
5.82	Ki	1500	nM	CHEMBL4211240
5.82	Ki	1500	nM	CHEMBL4863108
5.82	IC50	1500	nM	CHEMBL5028256
5.81	IC50	1560	nM	CHEMBL5028773
5.80	IC50	1570	nM	CHEMBL4861066
5.76	Ki	1750	nM	CHEMBL5028773
5.72	Ki	1920	nM	CHEMBL5027925
5.70	Ki	2000	nM	CHEMBL4847066
5.65	Ki	2260	nM	CHEMBL5028256
5.64	IC50	2310	nM	CHEMBL4203193
5.62	IC50	2370	nM	CHEMBL4847066
5.62	Ki	2400	nM	CHEMBL4852575
5.62	IC50	2380	nM	CHEMBL5028148
5.58	IC50	2630	nM	CHEMBL5028256
5.55	IC50	2800	nM	CHEMBL4203033
5.54	IC50	2900	nM	CHEMBL2047314
5.44	IC50	3630	nM	CHEMBL4863108
5.43	IC50	3740	nM	CHEMBL5028737
5.37	Ki	4300	nM	CHEMBL4853943
5.36	IC50	4400	nM	CHEMBL4215383
5.35	Ki	4440	nM	CHEMBL2011840
5.30	IC50	5060	nM	CHEMBL5027925
5.27	IC50	5420	nM	CHEMBL5027925
5.22	IC50	6000	nM	CHEMBL4206799

PubChem BioAssay actives

47 with measured affinity, of 143 total; 40 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
(4S)-3-[6-[[(1S)-1-[4-(2-methoxyphenyl)phenyl]ethyl]amino]pyrazin-2-yl]-4-propan-2-yl-1,3-oxazolidin-2-one	1956592: Inhibition of KLK6 (unknown origin)	ic50	0.0025	uM
[3-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-1,1,1-trifluoro-3-oxopropan-2-yl] 2-(2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.0180	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(6-carbamimidoyl-2-methyl-1H-indol-3-yl)acetate	1387153: Inhibition of KLK6 (unknown origin) expressed in Pichia pastoris pre-incubated for 10 mins before Boc-ValProArg-AMC substrate addition and measured after 30 mins by fluorescence based assay	ic50	0.0230	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(5-carbamimidoyl-2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.1000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.1000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(6-ethynyl-2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.1300	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.1300	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-ethynyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.1500	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.1900	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(5-ethynyl-2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.2500	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(5-chloro-2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.2500	uM
2-(2-methyl-1H-indol-3-yl)-N-[2-[(5-methyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl]acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.2900	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.4900	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methylindol-1-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.6400	uM
N-[4-(aminomethyl)phenyl]-3-hydroxynaphthalene-2-carboxamide;hydrochloride	1772341: Non-competitive inhibition of KLK6 (unknown origin) using Boc-QAR-AMC as substrate incubated for 30 mins by Dixon plot analysis	ki	0.8000	uM
2-[[4-(aminomethyl)phenyl]carbamoyl]-1-[(1-benzylimidazol-2-yl)methyl]pyridin-1-ium-3-olate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.8900	uM
N-[4-(aminomethyl)phenyl]-1-hydroxy-6-methoxynaphthalene-2-carboxamide;hydrochloride	1772342: Competitive inhibition of KLK6 (unknown origin) using Boc-QAR-AMC as substrate incubated for 30 mins by Dixon plot analysis	ki	1.0000	uM
2-(6-carbamimidoyl-2-methyl-1H-indol-3-yl)-N-[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl]acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	1.2000	uM
N-[2-[(4-methyl-3-phenyl-1,2-oxazol-5-yl)amino]-2-oxoethyl]-2-(2-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	1.2000	uM
2-(2-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-N-[2-oxo-2-[(1,3,5-trimethylpyrazol-4-yl)amino]ethyl]acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	1.4000	uM
N-[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-chlorobenzamide	1387134: Inhibition of human KLK6 expressed in baculovirus/insect cell line system using Abz-KLRSSKQ-EDDnp substrate	ki	1.5000	uM
N-[4-(aminomethyl)phenyl]-2-hydroxy-4-propan-2-ylbenzamide;hydrochloride	1772342: Competitive inhibition of KLK6 (unknown origin) using Boc-QAR-AMC as substrate incubated for 30 mins by Dixon plot analysis	ki	1.5000	uM
5-[[(3S)-3-[benzyl-(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide	669778: Inhibition of N-terminus His6-tagged human kallikrein 6 expressed in baculovirus infected insect sf9 cells using Boc-Phe-Ser-Arg-AMC as substrate by fluorescence analysis	ic50	1.5000	uM
N-[4-(aminomethyl)phenyl]-2-hydroxy-4-methylbenzamide;hydrochloride	1772342: Competitive inhibition of KLK6 (unknown origin) using Boc-QAR-AMC as substrate incubated for 30 mins by Dixon plot analysis	ki	2.0000	uM
[3-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-1,1,1-trifluoro-3-oxopropan-2-yl] 2-(2-methyl-1H-indol-3-yl)propanoate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	2.3100	uM
N-[4-(aminomethyl)phenyl]-1-hydroxynaphthalene-2-carboxamide;hydrochloride	1772342: Competitive inhibition of KLK6 (unknown origin) using Boc-QAR-AMC as substrate incubated for 30 mins by Dixon plot analysis	ki	2.4000	uM
N-[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)-methylamino]-2-oxoethyl]-2-(2-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	2.8000	uM
4-[[(3S)-3-[(7-methoxynaphthalen-2-yl)sulfonyl-(thiophen-3-ylmethyl)amino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide	669778: Inhibition of N-terminus His6-tagged human kallikrein 6 expressed in baculovirus infected insect sf9 cells using Boc-Phe-Ser-Arg-AMC as substrate by fluorescence analysis	ic50	2.9000	uM
N-[4-(aminomethyl)phenyl]-5-tert-butyl-2-hydroxybenzamide;hydrochloride	1772342: Competitive inhibition of KLK6 (unknown origin) using Boc-QAR-AMC as substrate incubated for 30 mins by Dixon plot analysis	ki	4.3000	uM
[2-(4-morpholin-4-ylanilino)-2-oxoethyl] 2-(2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	4.4000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	6.0000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(1,2-dimethylindol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	6.2000	uM
2-(2-methyl-1H-indol-3-yl)-N-[2-oxo-2-[(1-phenylpyrazol-4-yl)amino]ethyl]acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	6.9900	uM
2-(2-methyl-1H-indol-3-yl)-N-[2-[(3-methyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl]acetamide	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	7.5000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(4-chloro-2-methyl-1H-indol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	7.6000	uM
5-[[(3S)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide	669778: Inhibition of N-terminus His6-tagged human kallikrein 6 expressed in baculovirus infected insect sf9 cells using Boc-Phe-Ser-Arg-AMC as substrate by fluorescence analysis	ic50	7.7500	uM
5-[[(3S)-3-[(7-methoxynaphthalen-2-yl)sulfonyl-methylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide	669778: Inhibition of N-terminus His6-tagged human kallikrein 6 expressed in baculovirus infected insect sf9 cells using Boc-Phe-Ser-Arg-AMC as substrate by fluorescence analysis	ic50	8.2000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-methylbenzimidazol-1-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	8.9000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(2-oxo-1,3-benzoxazol-3-yl)acetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	9.0000	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-phenylacetate	1387137: Inhibition of His-6-tagged human KLK6 R74G/R76Q/N132Q mutant expressed in Escherichia coli DH10 pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Calcitriol	increases expression, increases reaction, affects cotreatment	5
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Cisplatin	affects expression, affects response to substance	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
sodium arsenate	decreases expression, increases abundance	1
titanium dioxide	increases expression	1
sodium arsenite	affects methylation	1
hydroquinone	increases expression	1
4-nonylphenol	affects cotreatment, decreases expression	1
seocalcitol	increases expression	1
4-tert-octylphenol	affects cotreatment, decreases expression	1
entinostat	increases expression	1
ICG 001	increases expression	1
bisphenol S	decreases expression	1
(+)-JQ1 compound	decreases 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
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Zoledronic Acid	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cytarabine	decreases expression	1
Endosulfan	increases expression	1
Fluorouracil	decreases expression, affects response to substance	1
Ketoconazole	increases expression, increases reaction	1
Methotrexate	affects response to substance	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

39 unique, capped per target: 39 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2051716	Binding	Inhibition of N-terminus His6-tagged human kallikrein 6 expressed in baculovirus infected insect sf9 cells using Boc-Phe-Ser-Arg-AMC as substrate by fluorescence analysis	Virtual Screening and X-ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group. — ACS Med Chem Lett

Clinical trials (associated diseases)

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