KLK11

Summary

KLK11 (kallikrein related peptidase 11, HGNC:6359) is a protein-coding gene on chromosome 19q13.41, encoding Kallikrein-11 (Q9UBX7). Possible multifunctional protease.

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternate splicing and the use of alternate promoters results in multiple transcript variants encoding distinct isoforms which are differentially expressed.

Source: NCBI Gene 11012 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ichthyosis with erythrokeratoderma (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 60 total — 2 pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• MANE Select transcript: NM_001136032

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6359
Approved symbol	KLK11
Name	kallikrein related peptidase 11
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	TLSP
Ensembl gene	ENSG00000167757
Ensembl biotype	protein_coding
OMIM	604434
Entrez	11012

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000319720, ENST00000319756, ENST00000391804, ENST00000453757, ENST00000593681, ENST00000594458, ENST00000594768, ENST00000594827, ENST00000598799, ENST00000600362, ENST00000601671, ENST00000860360, ENST00000860361, ENST00000860362, ENST00000860363, ENST00000860364, ENST00000860365, ENST00000860366, ENST00000860367, ENST00000860368, ENST00000860369, ENST00000860370, ENST00000953356, ENST00000953357

RefSeq mRNA: 4 — MANE Select: NM_001136032 NM_001136032, NM_001167605, NM_006853, NM_144947

CCDS: CCDS12818, CCDS12819, CCDS54297

Canonical transcript exons

ENST00000453757 — 6 exons

Exon	Start	End
ENSE00000722623	51024638	51024794
ENSE00001763564	51026538	51026616
ENSE00003499306	51025592	51025666
ENSE00003501037	51024045	51024310
ENSE00003551036	51023092	51023228
ENSE00003553347	51022236	51022697

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 99.47.

FANTOM5 (CAGE): breadth broad, TPM avg 9.8324 / max 829.0796, expressed in 317 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182351	8.6731	302
182356	0.3844	74
182350	0.2585	135
182357	0.1490	57
182354	0.1287	35
182348	0.0937	67
182347	0.0392	17
182353	0.0283	16
182349	0.0272	11
182352	0.0207	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.47	gold quality
esophagus mucosa	UBERON:0002469	98.67	gold quality
gingival epithelium	UBERON:0001949	98.63	gold quality
gingiva	UBERON:0001828	98.52	gold quality
skin of abdomen	UBERON:0001416	98.39	gold quality
upper arm skin	UBERON:0004263	98.18	gold quality
skin of leg	UBERON:0001511	98.13	gold quality
penis	UBERON:0000989	97.82	gold quality
oral cavity	UBERON:0000167	97.48	gold quality
zone of skin	UBERON:0000014	97.45	gold quality
pharyngeal mucosa	UBERON:0000355	97.31	gold quality
mammalian vulva	UBERON:0000997	97.23	gold quality
tongue squamous epithelium	UBERON:0006919	96.93	gold quality
cervix epithelium	UBERON:0004801	96.87	gold quality
squamous epithelium	UBERON:0006914	96.57	gold quality
gall bladder	UBERON:0002110	96.53	gold quality
cervix squamous epithelium	UBERON:0006922	96.21	gold quality
mouth mucosa	UBERON:0003729	95.99	gold quality
esophagus squamous epithelium	UBERON:0006920	95.73	gold quality
minor salivary gland	UBERON:0001830	95.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.54	gold quality
epithelium of esophagus	UBERON:0001976	95.42	gold quality
skin of hip	UBERON:0001554	95.16	gold quality
epithelium of bronchus	UBERON:0002031	95.16	gold quality
bronchus	UBERON:0002185	95.07	gold quality
upper leg skin	UBERON:0004262	95.03	gold quality
saliva-secreting gland	UBERON:0001044	94.91	gold quality
germinal epithelium of ovary	UBERON:0001304	94.86	gold quality
bronchial epithelial cell	CL:0002328	94.76	gold quality
nipple	UBERON:0002030	93.09	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	490.31
E-MTAB-8142	yes	121.01
E-CURD-114	yes	66.25
E-MTAB-8410	yes	20.91
E-HCAD-1	yes	8.05
E-GEOD-130148	yes	4.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting KLK11, 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-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-6755-3P	98.61	66.90	834
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-759	96.16	66.77	873

Literature-anchored findings (GeneRIF, showing 35)

• may be useful marker for distinguishing prostate cancer and benign prostatic hypertrophy (PMID:11550212)
• Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma. (PMID:11782391)
• Hippostasin isoform 3 may play a role in the prostate, including reproductive and/or tumorigenic functions. (PMID:12539228)
• There is a significant association between lower expression of prostate-type KLK11 and higher tumor stage, Gleason score, and tumor grade. (PMID:12736044)
• hK11 is a novel, independent marker of favorable prognosis in patients with ovarian cancer (PMID:12845660)
• KLK11 expression may play an important role in ovarian cancer development (PMID:15102682)
• Kallikrein 11 is an independent marker of favorable prognosis in ovarian cancer patients. (PMID:15329323)
• KLK11 was found to be highly expressed in 43/66 (65%) of prostate cancer samples (PMID:15893744)
• results suggest a co-regulation of KLK10 and KLK11 expression in lung and a lack of KLK10 suppressor role in non-small-cell lung cancer (PMID:16800740)
• The gene promoter regions of kallikrein and the corresponding transcriptional initiation sites were studied. (PMID:16911518)
• The hormone-specific upregulation of PSA, KLK10 and KLK11 in the breast cancer cell line T47D is dependent on major intracellular signaling pathways. (PMID:18515984)
• hK11 may be another prognostic biomarker of low rectal carcinoma. Strong positive hK11 staining associated with various clinicopathologic features. Patients with weak hK11 positive expression showed better survival rates. (PMID:19184568)
• Treatment of PC3 prostate cancer cells with mitoxantrone, etoposide, doxorubicin and carboplatin induces distinct alterations in the expression of kallikreins 5 and 11. (PMID:19190824)
• the up-regulation of TMPRSS2 and the down-regulation of KLK11 in advanced and more aggressive tumors may open the feasibility of being used as biomarkers distinguishing the tumor aggressiveness as well as novel prognostic indicators for prostate cancer. (PMID:19242826)
• synergistic effects between estrogens and androgens on estrogen-sensitive genes may have implications on the role of the kallikreins 10, 11, and 14 in associated risk of breast cancer and progression. (PMID:19383315)
• Data show that it was unable to distinguish men with and without prostate cancer using multiple kallikreins as urinary biomarkers. (PMID:19560453)
• For the first time, we report lower expression of KLK11 in CaP compared to BPH and slight upregulation of KLK11 in advanced tumors compared to localized ones (PMID:21520985)
• Low KLK11 protein expression is associated with gastric cancer. (PMID:21618246)
• Patients harboring KLK11-positive tumors had a significantly decreased risk of death. (PMID:22429520)
• Human airway trypsin-like protease can stimulate mucin5AC hypersecretion through a PAR2-mediated signaling pathway in 16HBE cells. (PMID:23602830)
• Our data showed that UVB-induced TSLP might increase secretion of the T-helper type 2-attracting chemokine (c-c motif) ligand 17 by human dendritic cells. (PMID:23639975)
• HOXB8 and KLK11 may be classified as valuable biomarkers, as they can predict the effects of FOLFOX4 chemotherapy in primary advanced colorectal cancer patients (PMID:23647300)
• hK11 expression in gastric cancer appears to be associated with a better prognosis. hK11 may be a prognostic biomarker of gastric cancer. (PMID:24169449)
• The aim of this study was to monitor serum levels of two microRNAs (miR-21 and miR-141) and three kallikreins (hK3/PSA, hK11, and hK13) before and 1, 5, and 30 days after radical prostatectomy. (PMID:24288670)
• KLK11 mRNA expression could be considered as a new molecular prognostic biomarker in colorectal adenocarcinoma (PMID:25123036)
• Variations in KLK15, but not KLK11 expression were significantly associated with prognosis in gastric cancer (PMID:26224476)
• 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)
• novel KLK11 and KLK12 splice variants represent new potential cancer biomarkers (PMID:29874189)
• The functional role of glycosylation in prostate-specific KLK11 could pave the way to a deeper understanding of their biology and to medical applications. (PMID:29975661)
• Diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma. (PMID:33015784)
• KLK11 acts as a tumor-inhibitor in laryngeal squamous cell carcinoma through the inactivation of Akt/Wnt/beta-catenin signaling. (PMID:33420975)
• KLK11 promotes the activation of mTOR and protein synthesis to facilitate cardiac hypertrophy. (PMID:34059001)
• Kallikrein-11, in Association with Coiled-Coil Domain Containing 25, as a Potential Prognostic Marker for Cholangiocarcinoma with Lymph Node Metastasis. (PMID:34067437)
• Kallikrein 11 Down-regulation in Breast Carcinoma: Correlation With Prognostic Parameters. (PMID:34697154)
• miR-1304 targets KLK11 to regulate gastric cancer cell proliferation through the mTOR signaling pathway. (PMID:37971062)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klk11	ENSMUSG00000067616
rattus_norvegicus	Klk11	ENSRNOG00000018742
drosophila_melanogaster	CG9673	FBGN0030775
drosophila_melanogaster	CG4477	FBGN0035971
drosophila_melanogaster	CG17404	FBGN0038001
drosophila_melanogaster	CG12256	FBGN0038002
drosophila_melanogaster	CG3916	FBGN0038003
drosophila_melanogaster	CG17477	FBGN0038479
drosophila_melanogaster	CG4053	FBGN0038482
drosophila_melanogaster	CG31269	FBGN0051269
drosophila_melanogaster	CG32808	FBGN0052808
drosophila_melanogaster	Phae2	FBGN0263235
drosophila_melanogaster	Send2	FBGN0264253

Paralogs (12): PRSS54 (ENSG00000103023), KLK14 (ENSG00000129437), KLK8 (ENSG00000129455), TMPRSS4 (ENSG00000137648), KLK3 (ENSG00000142515), KLK1 (ENSG00000167748), KLK4 (ENSG00000167749), KLK2 (ENSG00000167751), KLK5 (ENSG00000167754), KLK7 (ENSG00000169035), KLK12 (ENSG00000186474), PRSS58 (ENSG00000258223)

Protein

Protein identifiers

Kallikrein-11 — Q9UBX7 (reviewed: Q9UBX7)

Alternative names: Hippostasin, Serine protease 20, Trypsin-like protease

All UniProt accessions (7): Q9UBX7, A0A0A0MR55, A0A1R3UDR5, M0QYW4, M0QZI8, M0QZV0, M0R151

UniProt curated annotations — full annotation on UniProt →

Function. Possible multifunctional protease. Efficiently cleaves ‘bz-Phe-Arg-4-methylcoumaryl-7-amide’, a kallikrein substrate, and weakly cleaves other substrates for kallikrein and trypsin. Cleaves synthetic peptides after arginine but not lysine residues.

Subcellular location. Secreted Golgi apparatus. Secreted.

Tissue specificity. Expressed in brain, skin and prostate. Isoform 1 is expressed preferentially in brain. Isoform 2 is expressed in prostate. Present in seminal plasma at concentrations ranging from 2 to 37 microg/mL (at protein level).

Post-translational modifications. About 40% of KLK11 is inactivated by internal cleavage after Arg-188. This proteolytic inactivation may be effected by plasminogen.

Disease relevance. Ichthyosis with erythrokeratoderma (IEKD) [MIM:620507] An autosomal dominant genodermatosis characterized by early-onset ichthyosiform erythroderma with excessive skin scaling and peeling, and erythematous hyperkeratotic plaques. Lesions are present at birth or appear soon after. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Localized in the prostate secretory epithelium.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UBX7-2	2	yes
Q9UBX7-1	1
Q9UBX7-3	3
Q9UBX7-4	4

RefSeq proteins (4): NP_001129504, NP_001161077, NP_006844, NP_659196 (=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 3.4.21.35 — tissue kallikrein (BRENDA: 12 organisms, 294 substrates, 207 inhibitors, 205 Km, 182 kcat entries)
• EC 3.4.21.B42 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
DL-VAL-LEU-ARG-P-NITROANILIDE	0.12–58.8	6
PRO-PHE-ARG-4-METHYLCOUMARIN 7-AMIDE	0.07–0.114	5
N-ALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.08–0.333	4
N-ALPHA-TOSYL-L-ARGININE METHYL ESTER	0.022–0.117	4
SUCCINYL-VAL-PRO-PHE-THIOBENZYL ESTER	0.516–0.842	4
D-PRO-PHE-ARG-4-METHYLCOUMARIN-7-AMIDE	0.0002–0.0031	3
D-PRO-PHE-PHE-4-METHYLCOUMARIN-7-AMIDE	0.001–0.07	3
D-VAL-LEU-ARG-P-NITROANILIDE	0.0183–28.4	3
O-AMINOBENZOYL-GFSPFRSVTVQ-ETHYLENEDIAMINE 2,4-D	0.0002–0.0025	3
O-AMINOBENZOYL-MTEMARRPQ-ETHYLENEDIAMINE 2,4-DIN	0.003–0.0073	3
ABZ-KLRSSQ-EDDNP	0.0006	2
ACETYL-ALA-ARG METHYL ESTER	0.6–1.14	2
ACETYL-PHE-ARG METHYL ESTER	0.0244–0.0311	2
O-AMINOBENZOYL-FRSSR-N-(2,4-DINITROPHENYL)ETHYLE	0.0002–0.0006	2
O-AMINOBENZOYL-FRSVQ-N-(2,4-DINITROPHENYL)ETHYLE	0.0009–0.0073	2

UniProt features (26 total): disulfide bond 6, sequence variant 5, glycosylation site 4, chain 3, active site 3, splice variant 2, signal peptide 1, propeptide 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBX7-F1	83.08	0.64

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): 94 (charge relay system); 142 (charge relay system); 235 (charge relay system)

Disulfide bonds (6): 60–195, 79–95, 167–269, 174–241, 206–220, 231–256

Glycosylation sites (4): 197, 213, 242, 131

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, CHANDRAN_METASTASIS_DN, ONDER_CDH1_TARGETS_3_DN, GOBP_PROTEIN_MATURATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, MARTIN_VIRAL_GPCR_SIGNALING_UP, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, MODULE_88, MODULE_6, MODULE_48, MODULE_95, GOCC_SECRETORY_VESICLE

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

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

GO Cellular Component (5): obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), secretory granule (GO:0030141), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1080 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLK11	TSLP	Q969D9	865
KLK11	CRLF2	Q9HC73	840
KLK11	IL7R	P16871	778
KLK11	MEP1A	Q16819	561
KLK11	TGM4	P49221	451
KLK11	IL31	Q6EBC2	449
KLK11	D6RI10	D6RI10	449
KLK11	ZFYVE9	O95405	446
KLK11	NR1I2	O75469	442
KLK11	FURIN	P09958	437
KLK11	IL7	P13232	432
KLK11	HTRA1	Q92743	426
KLK11	IL33	O95760	423
KLK11	VIM	P08670	414
KLK11	KLKB1	P03952	413

IntAct

5 interactions, top by confidence:

A	B	Type	Score
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
KLK11	DENND11	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SPINT2		psi-mi:“MI:0914”(association)	0.350

BioGRID (65): TUBB3 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), AP3S1 (Affinity Capture-MS), SPSB3 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), NEU3 (Affinity Capture-MS), CHD1L (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), TBL3 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), VMP1 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), POLE2 (Affinity Capture-MS)

ESM2 similar proteins: A7WPL7, O43240, O46683, O60259, O88780, P07288, P09582, P09650, P10144, P15944, P19236, P20151, P20718, P21842, P23946, P24158, P33619, P49862, P50341, P50342, P51124, P52195, P56435, P79204, P80219, P83748, Q03238, Q07276, Q14B24, Q28773, Q61096, Q61955, Q6DT45, Q6IE59, Q6UWY2, Q76B45, Q7JIG6, Q92876, Q9BQR3, Q9BZJ3

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	37
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2579682	NM_001136032.3(KLK11):c.53G>A (p.Gly18Glu)	Pathogenic
2579683	NM_001136032.3(KLK11):c.52G>A (p.Gly18Arg)	Pathogenic

SpliceAI

967 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51023087:CTGA:C	donor_loss	1.0000
19:51023088:TGACC:T	donor_loss	1.0000
19:51023090:AC:A	donor_loss	1.0000
19:51023091:C:CG	donor_loss	1.0000
19:51023114:T:TA	donor_gain	1.0000
19:51023224:GCGTA:G	acceptor_gain	1.0000
19:51023225:CGTA:C	acceptor_gain	1.0000
19:51023225:CGTAC:C	acceptor_gain	1.0000
19:51023226:GTA:G	acceptor_gain	1.0000
19:51023226:GTAC:G	acceptor_loss	1.0000
19:51023227:TA:T	acceptor_gain	1.0000
19:51023227:TACTG:T	acceptor_loss	1.0000
19:51023229:C:CA	acceptor_loss	1.0000
19:51023229:C:CC	acceptor_gain	1.0000
19:51024044:CA:C	donor_gain	1.0000
19:51024637:CGG:C	donor_gain	1.0000
19:51027455:A:AC	donor_gain	1.0000
19:51027456:C:CC	donor_gain	1.0000
19:51027456:CTGG:C	donor_gain	1.0000
19:51022696:CC:C	acceptor_gain	0.9900
19:51022697:CC:C	acceptor_gain	0.9900
19:51024043:A:AC	donor_gain	0.9900
19:51024044:C:CC	donor_gain	0.9900
19:51024131:ACAG:A	donor_gain	0.9900
19:51024132:CAGC:C	donor_gain	0.9900
19:51024308:CGG:C	acceptor_gain	0.9900
19:51024311:C:CC	acceptor_gain	0.9900
19:51024633:CCCA:C	donor_gain	0.9900
19:51024636:A:AC	donor_gain	0.9900
19:51024637:C:CC	donor_gain	0.9900

AlphaMissense

1628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51024067:C:A	W179C	0.999
19:51024067:C:G	W179C	0.999
19:51022572:C:A	W274C	0.998
19:51022572:C:G	W274C	0.998
19:51023129:C:G	C220S	0.998
19:51023130:A:T	C220S	0.998
19:51022641:C:A	W251C	0.997
19:51022641:C:G	W251C	0.997
19:51022693:T:A	D234V	0.997
19:51023171:C:G	C206S	0.997
19:51023172:A:T	C206S	0.997
19:51024179:T:A	D142V	0.997
19:51024179:T:G	D142A	0.997
19:51022687:C:A	G236V	0.996
19:51022688:C:A	G236W	0.996
19:51022693:T:G	D234A	0.996
19:51023096:C:G	C231S	0.996
19:51023096:C:T	C231Y	0.996
19:51023097:A:T	C231S	0.996
19:51024069:A:G	W179R	0.996
19:51024069:A:T	W179R	0.996
19:51024214:G:C	F130L	0.996
19:51024214:G:T	F130L	0.996
19:51024216:A:G	F130L	0.996
19:51024695:C:G	C79S	0.996
19:51024696:A:T	C79S	0.996
19:51022687:C:T	G236E	0.995
19:51023130:A:G	C220R	0.995
19:51024082:G:C	C174W	0.995
19:51024178:G:C	D142E	0.995

dbSNP variants (sampled 300 via entrez): RS1000229842 (19:51022644 G>A), RS1000324018 (19:51027142 G>A,C,T), RS1000806507 (19:51022105 G>A,T), RS1000852292 (19:51022438 G>A,T), RS1001555186 (19:51023411 G>C,T), RS1001640960 (19:51025840 A>ATATCTTAGGTGTC), RS1001720617 (19:51027696 CTA>C), RS1001741869 (19:51023000 G>A,C), RS1002895439 (19:51028740 G>A), RS1002933487 (19:51028567 G>A), RS1002987143 (19:51028915 C>T), RS1003131854 (19:51024131 A>C,T), RS1003709052 (19:51024941 G>T), RS1003722245 (19:51025092 C>G,T), RS1003769661 (19:51025250 T>C)

Disease associations

OMIM: gene MIM:604434 | disease phenotypes: MIM:620507

GenCC curated gene-disease

Disease	Classification	Inheritance
ichthyosis with erythrokeratoderma	Strong	Autosomal dominant

Mondo (1): ichthyosis with erythrokeratoderma (MONDO:0957783)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000962	Hyperkeratosis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001036	Parakeratosis
HP:0001803	Nail pits
HP:0001820	Leukonychia
HP:0003577	Congenital onset
HP:0007431	Congenital ichthyosiform erythroderma
HP:0007447	Diffuse palmoplantar hyperkeratosis
HP:0010783	Erythema
HP:0025092	Epidermal acanthosis
HP:0040189	Scaling skin

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003831_42	Asthma	7.000000e-08
GCST006585_1256	Blood protein levels	2.000000e-121
GCST006585_390	Blood protein levels	1.000000e-261
GCST009567_1	kallikrein-11 levels	5.000000e-18
GCST009731_63	Blood protein levels in cardiovascular risk	7.000000e-76

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010573	kallikrein-11 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3031 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression, increases expression, affects cotreatment	3
Estradiol	decreases expression, increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects response to substance	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
CHEMBL4831731	Binding	Inhibition of KLK11 (unknown origin) assessed as inhibition of release of AMC fluorescent product using H-VPR-AMC as substrate at 10 uM incubated for 30 mins by microplate reader relative to control	Identification of First-in-Class Inhibitors of Kallikrein-Related Peptidase 6 That Promote Oligodendrocyte Differentiation. — J Med Chem

Clinical trials (associated diseases)

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