KLK9

Summary

KLK9 (kallikrein related peptidase 9, HGNC:6370) is a protein-coding gene on chromosome 19q13.41, encoding Kallikrein-9 (Q9UKQ9).

The protein encoded by this gene is a kallikrein-related serine protease. This gene is activated by steroid hormones in a human breast cancer cell line, making it a good marker for cancer detection. The encoded protein is found primarily in the cytoplasm.

Source: NCBI Gene 284366 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_012315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6370
Approved symbol	KLK9
Name	kallikrein related peptidase 9
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	KLK-L3
Ensembl gene	ENSG00000213022
Ensembl biotype	protein_coding
OMIM	605504
Entrez	284366

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 nonsense_mediated_decay, 1 protein_coding

ENST00000544410, ENST00000594211

RefSeq mRNA: 1 — MANE Select: NM_012315 NM_012315

CCDS: CCDS12816

Canonical transcript exons

ENST00000594211 — 5 exons

Exon	Start	End
ENSE00003033805	51009505	51009592
ENSE00003513687	51002508	51003260
ENSE00003515228	51009183	51009339
ENSE00003587910	51006458	51006723
ENSE00003642616	51003704	51003840

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 76.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2538 / max 108.7131, expressed in 48 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182324	0.1098	33
182325	0.0869	28
182326	0.0528	24
182323	0.0043	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	76.13	gold quality
zone of skin	UBERON:0000014	73.87	gold quality
skin of abdomen	UBERON:0001416	70.87	gold quality
esophagus mucosa	UBERON:0002469	66.92	gold quality
lower esophagus mucosa	UBERON:0035834	62.85	gold quality
tonsil	UBERON:0002372	46.76	gold quality
vagina	UBERON:0000996	46.66	gold quality
esophagus	UBERON:0001043	45.98	gold quality
right uterine tube	UBERON:0001302	40.27	silver quality
bone marrow cell	CL:0002092	39.35	gold quality
ectocervix	UBERON:0012249	37.45	gold quality
minor salivary gland	UBERON:0001830	37.40	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
saliva-secreting gland	UBERON:0001044	36.67	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	34.77	gold quality
uterine cervix	UBERON:0000002	34.09	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	32.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
fallopian tube	UBERON:0003889	32.00	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.84	silver quality
urinary bladder	UBERON:0001255	29.42	gold quality
liver	UBERON:0002107	29.26	gold quality
smooth muscle tissue	UBERON:0001135	28.71	silver quality
multicellular organism	UBERON:0000468	28.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting KLK9, 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-5010-3P	99.83	70.60	2357
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-6822-3P	96.60	66.06	680
HSA-MIR-431-5P	96.16	66.50	652
HSA-MIR-3178	89.40	60.05	100
HSA-MIR-25-5P	87.02	64.95	84
HSA-MIR-10394-3P	85.92	60.60	39
HSA-MIR-1471	77.94	66.74	5
HSA-MIR-4634	77.73	62.36	14

Literature-anchored findings (GeneRIF, showing 4)

• the serum level has the potential to be used as a biomarker for asthma (PMID:25747782)
• Data demonstrate that elevated levels of KLK6, KLK7 and KLK9 proteins are associated with poor glioblastoma patients survival. (PMID:26231762)
• Data suggest that mature KLK9 (kallikrein 9) is a glycosylated chymotrypsin-like enzyme with strong preference for tyrosine over phenylalanine at P1 cleavage position; substrate specificity of KLK9 appears to extend to KLK10 and midkine; enzyme activity is enhanced by Mg2+ and Ca2+, but is reversibly attenuated by Zn2+; KLK9 is inhibited in vitro by many naturally occurring or synthetic protease inhibitors. (PMID:28559305)
• Pronounced correlations between KLK10/KLK11 (rs = 0.647) and between KLK9/KLK15 (rs = 0.716) mRNA, but not between other combinations, indicate coordinate expression of distinct pairs of peptidases (PMID:29095848)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klk9	ENSMUSG00000047884
rattus_norvegicus	Klk9	ENSRNOG00000022313

Paralogs (14): PRSS33 (ENSG00000103355), PLAT (ENSG00000104368), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), PRSS50 (ENSG00000283706)

Protein

Protein identifiers

Kallikrein-9 — Q9UKQ9 (reviewed: Q9UKQ9)

Alternative names: Kallikrein-like protein 3

All UniProt accessions (2): Q2XQG6, Q9UKQ9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Skin, thymus, trachea, cerebellum and spinal cord.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKQ9-1	1	yes
Q9UKQ9-2	2

RefSeq proteins (1): NP_036447* (*=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.B40 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (17 total): disulfide bond 6, active site 3, glycosylation site 3, splice variant 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKQ9-F1	91.55	0.85

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 (3): 63 (charge relay system); 111 (charge relay system); 204 (charge relay system)

Disulfide bonds (6): 48–64, 136–238, 143–210, 175–189, 200–225, 29–164

Glycosylation sites (3): 131, 166, 211

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): CREL_01, GOCC_SECRETORY_GRANULE, LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, HUMMERICH_BENIGN_SKIN_TUMOR_UP, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, CEBPB_01, NFKB_Q6, GOBP_PROTEIN_MATURATION, GGARNTKYCCA_UNKNOWN, PITX2_Q2

GO Biological Process (2): proteolysis (GO:0006508), protein maturation (GO:0051604)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), secretory granule (GO:0030141), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
gene expression	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
endomembrane system	1
secretory vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLK9	S100A7A	Q86SG5	520
KLK9	CCDC73	Q6ZRK6	492
KLK9	PTPDC1	A2A3K4	476
KLK9	KRT16	P08779	445
KLK9	ERCC6L	Q2NKX8	426
KLK9	KLKB1	P03952	420
KLK9	KLK2	P20151	416
KLK9	KLK11	Q9UBX7	399
KLK9	KLK3	P07288	398
KLK9	KIF20A	O95235	369
KLK9	FABP5	Q01469	368
KLK9	OR52N4	Q8NGI2	367
KLK9	TAF7L	Q5H9L4	360
KLK9	WFDC6	Q9BQY6	359
KLK9	GPER1	Q99527	359

IntAct

21 interactions, top by confidence:

A	B	Type	Score
BAG4	KLK9	psi-mi:“MI:0915”(physical association)	0.370
BRMS1	KLK9	psi-mi:“MI:0915”(physical association)	0.370
CASP8	KLK9	psi-mi:“MI:0915”(physical association)	0.370
CCND1	KLK9	psi-mi:“MI:0915”(physical association)	0.370
CHEK2	KLK9	psi-mi:“MI:0915”(physical association)	0.370
ESR1	KLK9	psi-mi:“MI:0915”(physical association)	0.370
KLK9	ESR2	psi-mi:“MI:0915”(physical association)	0.370
PAX2	KLK9	psi-mi:“MI:0915”(physical association)	0.370
PTPRJ	KLK9	psi-mi:“MI:0915”(physical association)	0.370
TGFB1	KLK9	psi-mi:“MI:0915”(physical association)	0.370
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK9	POTEE	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
SLC25A6	A2ML1	psi-mi:“MI:0914”(association)	0.350
P2RX6	A2ML1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
INSR	ATOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), KLK9 (Two-hybrid), POTEE (Affinity Capture-MS), NRBP1 (Affinity Capture-MS), KLK9 (Affinity Capture-MS), KLK9 (Affinity Capture-MS), KLK9 (Affinity Capture-MS)

ESM2 similar proteins: A1A5C7, A5D7B1, A6H7A0, A6NCF5, A6QLN9, A8MUP2, D3YYU8, D3ZZ80, O43688, O75147, O88843, P08887, Q14CX5, Q3SZQ2, Q3UHH2, Q58CT4, Q5EA19, Q5R4Q7, Q5R7S9, Q5RCI5, Q5RFN0, Q5SP67, Q5SUV1, Q642A6, Q6IA17, Q6PCB0, Q7TPB4, Q86TI4, Q8BGR6, Q8BZI6, Q8K5A4, Q8N5I2, Q8N653, Q8R2Z5, Q8TBF2, Q8VE98, Q92737, Q969P0, Q96NJ5, Q96NT3

Diamond homologs: A0A1S4GMJ4, A6NIE9, A8JUP7, G3V801, O08762, O42207, O60235, P00741, P00745, P00762, P00765, P03951, P05049, P07477, P07478, P0CW18, P15120, P16292, P16295, P19799, P29786, P29787, P35030, P35039, P69525, P79953, Q14B25, Q14BX2, Q14C59, Q1JRP2, Q27081, Q28278, Q28315, Q28412, Q29463, Q2KJ63, Q2VG86, Q5G265, Q5U405, Q6BEA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

765 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51009181:A:AC	donor_gain	1.0000
19:51009181:ACGG:A	donor_gain	1.0000
19:51009182:C:CC	donor_gain	1.0000
19:51009182:CGG:C	donor_gain	1.0000
19:51009182:CGGC:C	donor_gain	1.0000
19:51003259:CC:C	acceptor_gain	0.9900
19:51003260:CC:C	acceptor_gain	0.9900
19:51009179:TCA:T	donor_loss	0.9900
19:51009182:CGGCT:C	donor_gain	0.9900
19:51003256:TCACC:T	acceptor_gain	0.9800
19:51003257:CACC:C	acceptor_gain	0.9800
19:51003257:CACCC:C	acceptor_gain	0.9800
19:51003261:C:A	acceptor_loss	0.9800
19:51003261:CTGT:C	acceptor_loss	0.9800
19:51003262:T:G	acceptor_loss	0.9800
19:51003836:CAGCG:C	acceptor_gain	0.9800
19:51006504:G:A	donor_gain	0.9800
19:51009174:GTCAC:G	donor_loss	0.9800
19:51009175:TCACT:T	donor_loss	0.9800
19:51009176:CACT:C	donor_loss	0.9800
19:51009176:CACTC:C	donor_loss	0.9800
19:51009177:ACTC:A	donor_loss	0.9800
19:51009179:T:TC	donor_loss	0.9800
19:51009180:CAC:C	donor_loss	0.9800
19:51009182:C:A	donor_loss	0.9800
19:51009182:CG:C	donor_gain	0.9800
19:51009336:TGCC:T	acceptor_gain	0.9800
19:51003261:C:CC	acceptor_gain	0.9700
19:51009499:CCTCA:C	donor_loss	0.9700
19:51009500:CTCA:C	donor_loss	0.9700

AlphaMissense

1627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51006480:C:A	W148C	0.999
19:51006480:C:G	W148C	0.999
19:51003135:C:A	W243C	0.996
19:51003135:C:G	W243C	0.996
19:51003741:C:G	C189S	0.996
19:51003742:A:T	C189S	0.996
19:51006592:T:A	D111V	0.994
19:51003250:C:A	G205V	0.993
19:51003251:C:A	G205W	0.993
19:51006593:C:G	D111H	0.993
19:51003783:C:G	C175S	0.992
19:51003784:A:T	C175S	0.992
19:51006482:A:G	W148R	0.992
19:51006482:A:T	W148R	0.992
19:51006591:G:C	D111E	0.992
19:51006591:G:T	D111E	0.992
19:51006627:G:C	F99L	0.992
19:51006627:G:T	F99L	0.992
19:51006629:A:G	F99L	0.992
19:51006592:T:G	D111A	0.991
19:51009192:C:G	C64S	0.991
19:51009193:A:T	C64S	0.991
19:51009240:C:T	C48Y	0.991
19:51009275:C:A	W36C	0.991
19:51009275:C:G	W36C	0.991
19:51003256:T:A	D203V	0.990
19:51003708:C:G	C200S	0.990
19:51003709:A:T	C200S	0.990
19:51006593:C:A	D111Y	0.990
19:51009192:C:T	C64Y	0.990

dbSNP variants (sampled 300 via entrez): RS1000135001 (19:51011515 T>C), RS1000252442 (19:51005912 T>A), RS1000805715 (19:51007069 A>C,T), RS1000920423 (19:51007213 T>C), RS1002068708 (19:51002576 C>T), RS1002248789 (19:51002313 T>TC), RS1002417323 (19:51007899 G>A), RS1002469539 (19:51007643 T>C), RS1002677113 (19:51002282 G>A), RS1003293162 (19:51003600 CCTT>C), RS1003473469 (19:51008977 C>G,T), RS1003855960 (19:51009015 G>A), RS1004390268 (19:51008004 T>C), RS1004457415 (19:51010361 C>T), RS1005077997 (19:51006336 T>C)

Disease associations

OMIM: gene MIM:605504 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
bisphenol A	increases methylation	1
sodium arsenate	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	affects response to substance	1
Tetrachlorodibenzodioxin	increases expression	1

Clinical trials (associated diseases)

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