LMTK2

Summary

LMTK2 (lemur tyrosine kinase 2, HGNC:17880) is a protein-coding gene on chromosome 7q21.3, encoding Serine/threonine-protein kinase LMTK2 (Q8IWU2). Phosphorylates PPP1C, phosphorylase b and CFTR.

The protein encoded by this gene belongs to the protein kinase superfamily and the protein tyrosine kinase family. It contains N-terminal transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity. This protein interacts with several other proteins, such as Inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosporylates other proteins, and is itself also phosporylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein involves in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis.

Source: NCBI Gene 22853 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 252 total
• Druggable target: yes
• MANE Select transcript: NM_014916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17880
Approved symbol	LMTK2
Name	lemur tyrosine kinase 2
Location	7q21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1079, KPI2, KPI-2, cprk, LMR2, BREK, AATYK2, PPP1R100
Ensembl gene	ENSG00000164715
Ensembl biotype	protein_coding
OMIM	610989
Entrez	22853

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000297293, ENST00000493372, ENST00000873831, ENST00000930919

RefSeq mRNA: 1 — MANE Select: NM_014916 NM_014916

CCDS: CCDS5654

Canonical transcript exons

ENST00000297293 — 14 exons

Exon	Start	End
ENSE00001086917	98106862	98107280
ENSE00001086918	98190728	98190877
ENSE00001086920	98191614	98194572
ENSE00001086923	98205464	98209638
ENSE00001131957	98203574	98203706
ENSE00001131981	98186877	98186998
ENSE00001131987	98185051	98185135
ENSE00001131994	98171541	98171674
ENSE00001131998	98159338	98159425
ENSE00001132003	98154758	98154876
ENSE00001320957	98203944	98204186
ENSE00003481678	98137315	98137442
ENSE00003531192	98141397	98141541
ENSE00003561051	98151382	98151455

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 96.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7155 / max 461.1191, expressed in 1791 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79807	19.6712	1788
79808	0.5463	176
79809	0.4980	206

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	96.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.63	gold quality
parietal lobe	UBERON:0001872	91.33	gold quality
postcentral gyrus	UBERON:0002581	91.24	gold quality
superior frontal gyrus	UBERON:0002661	89.60	gold quality
primary visual cortex	UBERON:0002436	89.14	gold quality
occipital lobe	UBERON:0002021	88.76	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.27	gold quality
pons	UBERON:0000988	88.18	gold quality
parotid gland	UBERON:0001831	87.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.31	gold quality
pharyngeal mucosa	UBERON:0000355	87.09	gold quality
secondary oocyte	CL:0000655	87.01	gold quality
epithelium of nasopharynx	UBERON:0001951	86.51	gold quality
esophagus squamous epithelium	UBERON:0006920	86.45	gold quality
prefrontal cortex	UBERON:0000451	86.36	gold quality
cortical plate	UBERON:0005343	86.28	gold quality
entorhinal cortex	UBERON:0002728	85.79	gold quality
frontal cortex	UBERON:0001870	85.70	gold quality
frontal lobe	UBERON:0016525	85.66	gold quality
endothelial cell	CL:0000115	84.78	gold quality
neocortex	UBERON:0001950	84.67	gold quality
jejunal mucosa	UBERON:0000399	84.52	gold quality
superior vestibular nucleus	UBERON:0007227	83.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.60	gold quality
right frontal lobe	UBERON:0002810	83.57	gold quality
colonic mucosa	UBERON:0000317	83.46	gold quality
cerebral cortex	UBERON:0000956	83.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.95	gold quality
amniotic fluid	UBERON:0000173	82.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1

miRNA regulators (miRDB)

139 targeting LMTK2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-8063	99.91	69.76	3146

Literature-anchored findings (GeneRIF, showing 19)

• KPI-2 is a kinase with sites to associate with PP1C and Inh2 to form a regulatory complex that is localized to membranes (PMID:12393858)
• Cprk is expressed in a number of tissues but is enriched in brain and muscle; Cprk displays catalytic activity in kinase assays and is itself phosphorylated by cdk5/p35; Cdk5/p35 inhibits cprk activity (PMID:12832520)
• BREK, Brain Enriched Kinase, is a new member of the family of protein serine/threonine kinases; plays important roles in NGF-TrkA signalling in the brain [BREK] (PMID:15005709)
• role of the segment KLHY in binding with protein phosphatase 1 (PMID:16428298)
• Myosin VI and LMTK2 are required for the transport of cargo, such as the Transferrin Receptor, from early endosomes to the endocytic recycling compartment. (PMID:18029400)
• Results show that BREK is critical for the transition of endocytosed membrane vesicles from early endosomes to recycling endosomes and also suggest an involvement of myosin VI in this pathway. (PMID:18429820)
• Data show that downregulation of myosin VI expression results in a significant reduction in PSA and VEGF secretion in LNCaP cells, and the intracellular targeting seems to involve myosin VI-interacting proteins, GIPC and LMTK2 and Dab2. (PMID:19855435)
• Low LMTK2 expression is associated with the development of prostate cancer. (PMID:20569440)
• We describe a new signalling pathway within the nervous system that links cdk5/p35 with phosphatase-1C and which has implications for a number of neuronal functions and neuronal dysfunction (PMID:22220831)
• The results indicate that lemur tyrosine kinase 2 is an integral membrane protein in which both the amino and carboxyl termini are exposed to the cytoplasm. Moreover, this topology places the kinase active site within the cytoplasm. (PMID:23114966)
• Data indicate that Lemur tyrosine kinase 2 (LMTK2) localizes at the plasma membrane and co-immunoprecipitates with cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells. (PMID:24727471)
• Lemur Tyrosine Kinase-2 (LMTK2), negatively regulates androgen-dependent and androgen-independent prostate cancer cell proliferation. In addition, LMTK2 also negatively regulates the androgen receptor transcriptional activity. (PMID:26008968)
• Mutation of the di-acidic export motif led to endoplasmic reticulum retention of LMTK2, and an increase in protein half-life. (PMID:26559041)
• both BIM and BCL2 proteins are regulated by LMTK2 in a GSK3beta- and PP1A-dependent manner. (PMID:28040547)
• LMTK2 binds to KLC1 to direct axonal transport of p35 and its loss may contribute to Alzheimer’s disease. (PMID:31068217)
• silencing of LMTK2 suppresses the proliferation and invasion of hepatocellular carcinoma cells. (PMID:31395338)
• Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC. (PMID:31722712)
• Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer’s disease and neocortical Lewy body disease. (PMID:31748522)
• Lemur tyrosine kinase 2 has a tumor-inhibition function in human glioblastoma by regulating the RUNX3/Notch pathway. (PMID:37271222)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmtk2	ENSDARG00000076324
mus_musculus	Lmtk2	ENSMUSG00000038970
rattus_norvegicus	Lmtk2	ENSRNOG00000025155

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078)

Protein

Protein identifiers

Serine/threonine-protein kinase LMTK2 — Q8IWU2 (reviewed: Q8IWU2)

Alternative names: Apoptosis-associated tyrosine kinase 2, Brain-enriched kinase, CDK5/p35-regulated kinase, Kinase/phosphatase/inhibitor 2, Lemur tyrosine kinase 2, Serine/threonine-protein kinase KPI-2

All UniProt accessions (1): Q8IWU2

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates PPP1C, phosphorylase b and CFTR.

Subunit / interactions. Interacts with PPP1C and inhibitor-2.

Subcellular location. Membrane.

Tissue specificity. Mainly expressed in skeletal muscle, and weakly in brain and pancreas.

Post-translational modifications. Autophosphorylated. Phosphorylated.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family.

RefSeq proteins (1): NP_055731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF07714

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (51 total): sequence variant 13, modified residue 11, region of interest 7, compositionally biased region 7, topological domain 3, sequence conflict 3, transmembrane region 2, binding site 2, chain 1, active site 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWU2-F1	47.41	0.15

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): 265 (proton acceptor)

Ligand- & substrate-binding residues (2): 143–151; 168

Post-translational modifications (11): 805, 806, 886, 1107, 1305, 1307, 1308, 1310, 1450, 1496, 1497

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): RNGTGGGC_UNKNOWN, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_PEPTIDYL_SERINE_MODIFICATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_IRON_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, PATIL_LIVER_CANCER, MARTINEZ_RB1_TARGETS_UP, E4F1_Q6, GOBP_RECEPTOR_METABOLIC_PROCESS, TGACATY_UNKNOWN, ATF4_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT_BETWEEN_ENDOSOMAL_COMPARTMENTS, GOBP_ENDOCYTIC_RECYCLING

GO Biological Process (8): receptor recycling (GO:0001881), protein phosphorylation (GO:0006468), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), endocytic recycling (GO:0032456), transferrin transport (GO:0033572), early endosome to late endosome transport (GO:0045022), protein autophosphorylation (GO:0046777)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein phosphatase inhibitor activity (GO:0004864), ATP binding (GO:0005524), myosin VI binding (GO:0070853), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): early endosome (GO:0005769), Golgi apparatus (GO:0005794), membrane (GO:0016020), growth cone (GO:0030426), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein phosphorylation	3
cytoplasm	3
protein kinase activity	2
endosome	2
endocytosis	1
receptor metabolic process	1
phosphorylation	1
protein modification process	1
peptidyl-serine modification	1
peptidyl-threonine modification	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
iron ion transport	1
protein transport	1
vesicle-mediated transport between endosomal compartments	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
myosin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
site of polarized growth	1
distal axon	1
somatodendritic compartment	1
cell body	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMTK2	PPP1R2	P41236	749
LMTK2	MSMB	P08118	726
LMTK2	EHBP1	Q8NDI1	689
LMTK2	TOM1	O60784	666
LMTK2	DAB2	P98082	639
LMTK2	JAZF1	Q86VZ6	638
LMTK2	PPP1CC	P36873	600
LMTK2	KLK3	P07288	555
LMTK2	CTBP2	P56545	552
LMTK2	TOM1L2	Q6ZVM7	534
LMTK2	PPP1CA	P08129	517
LMTK2	CPNE3	O75131	515
LMTK2	IL16	Q14005	491
LMTK2	SRD5A2	P31213	487
LMTK2	TMPRSS2	O15393	483
LMTK2	AMACR	Q9UHK6	483

IntAct

86 interactions, top by confidence:

A	B	Type	Score
PPP1CC	LMTK2	psi-mi:“MI:0915”(physical association)	0.860
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1R2	LMTK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.680
PPP1R2	LMTK2	psi-mi:“MI:0915”(physical association)	0.680
LMTK2	PPP1CA	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LMTK2	ATP9A	psi-mi:“MI:0915”(physical association)	0.400
PPP1CA	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PPP1CB	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PPP3CB	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PPM1A	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PPM1F	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PPM1K	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
ILKAP	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PTPN6	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PTPN12	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
DUSP6	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
DUSP14	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
DUSP19	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
STYX	LMTK2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (157): LMTK2 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), LMTK2 (Proximity Label-MS), LMTK2 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), PPP1CA (Two-hybrid), PPP1CB (Two-hybrid), PPP1CC (Two-hybrid), PPP3CB (Two-hybrid), PPM1A (Two-hybrid), PPM1F (Two-hybrid)

ESM2 similar proteins: A0JPP4, B9EKR1, O00592, O57604, P07141, P13611, P23471, P70628, P81282, Q17R60, Q1XI86, Q28858, Q2TA21, Q3TNW5, Q3UU94, Q3V1M1, Q52S86, Q569E4, Q58Y74, Q5JRA6, Q5XI99, Q62059, Q62656, Q68CR7, Q6MG22, Q6R8J2, Q6WRH9, Q6WRI0, Q71M36, Q7TST5, Q80XH2, Q86TY3, Q8BI84, Q8BT18, Q8IWU2, Q8JIR8, Q8JZQ0, Q8R1W8, Q90953, Q95KG7

Diamond homologs: A0JNB0, A1Y2K1, F8W3R9, O02466, O13147, O42422, O45539, O73798, O73878, O76997, P00523, P00529, P00530, P00541, P04629, P06213, P08069, P08922, P08941, P09208, P09759, P09769, P12931, P13368, P14085, P14616, P14617, P15054, P15127, P15208, P15209, P24062, P24604, P27446, P28693, P33497, P35739, P39688, P41239, P42159

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDK5	down-regulates	LMTK2	phosphorylation
CDK5	up-regulates	LMTK2	phosphorylation
LMTK2	“down-regulates activity”	CFTR	phosphorylation
LMTK2	“down-regulates activity”	PPP1CA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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
RHO GTPases activate PKNs	6	28.8×	2e-05
RAF activation	5	25.4×	3e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	11.7×	3e-03
G2/M Checkpoints	5	10.2×	4e-03
R-HSA-425393	5	9.8×	4e-03
SLC-mediated transmembrane transport	8	7.2×	2e-03
Transport of small molecules	11	4.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	10	24.9×	5e-09
transport across blood-brain barrier	6	12.1×	4e-03
MAPK cascade	6	10.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	207
Likely benign	14
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3178 predictions. Top by Δscore:

Variant	Effect	Δscore
7:98107278:CAGG:C	donor_loss	1.0000
7:98107280:GGTGA:G	donor_loss	1.0000
7:98107282:T:A	donor_loss	1.0000
7:98141391:TTTTA:T	acceptor_loss	1.0000
7:98141393:TTAG:T	acceptor_loss	1.0000
7:98141394:TA:T	acceptor_loss	1.0000
7:98141395:A:AG	acceptor_gain	1.0000
7:98141395:A:T	acceptor_loss	1.0000
7:98141395:AG:A	acceptor_gain	1.0000
7:98141396:G:GA	acceptor_gain	1.0000
7:98141396:GG:G	acceptor_gain	1.0000
7:98141396:GGA:G	acceptor_gain	1.0000
7:98141396:GGAA:G	acceptor_gain	1.0000
7:98141396:GGAAT:G	acceptor_gain	1.0000
7:98141537:TGTAG:T	donor_loss	1.0000
7:98141538:GTAG:G	donor_gain	1.0000
7:98141540:AGG:A	donor_loss	1.0000
7:98141542:GT:G	donor_loss	1.0000
7:98141543:T:G	donor_loss	1.0000
7:98151377:TACAG:T	acceptor_gain	1.0000
7:98151378:A:AG	acceptor_gain	1.0000
7:98151378:ACAGA:A	acceptor_gain	1.0000
7:98151379:C:G	acceptor_gain	1.0000
7:98151379:CAG:C	acceptor_gain	1.0000
7:98151380:A:AC	acceptor_loss	1.0000
7:98151380:A:AG	acceptor_gain	1.0000
7:98151380:AG:A	acceptor_gain	1.0000
7:98151380:AGAG:A	acceptor_gain	1.0000
7:98151380:AGAGG:A	acceptor_gain	1.0000
7:98151381:G:A	acceptor_gain	1.0000

AlphaMissense

9903 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:98186922:T:A	W308R	1.000
7:98186922:T:C	W308R	1.000
7:98186997:T:A	W333R	0.999
7:98186997:T:C	W333R	0.999
7:98190876:T:A	W383R	0.999
7:98190876:T:C	W383R	0.999
7:98141401:T:G	F79C	0.998
7:98186924:G:C	W308C	0.998
7:98186924:G:T	W308C	0.998
7:98190735:G:C	G336R	0.998
7:98190736:G:A	G336D	0.998
7:98191633:T:C	C390R	0.998
7:98191635:T:G	C390W	0.998
7:98191636:T:A	W391R	0.998
7:98191636:T:C	W391R	0.998
7:98191685:T:C	L407P	0.998
7:98191694:T:C	L410P	0.998
7:98191853:T:C	L463P	0.998
7:98193781:T:C	F1106L	0.998
7:98193783:C:A	F1106L	0.998
7:98193783:C:G	F1106L	0.998
7:98141400:T:C	F79L	0.997
7:98141402:T:A	F79L	0.997
7:98141402:T:G	F79L	0.997
7:98141430:T:C	F89L	0.997
7:98141432:C:A	F89L	0.997
7:98141432:C:G	F89L	0.997
7:98159400:T:C	L211P	0.997
7:98171637:G:T	G252W	0.997
7:98171641:T:C	L253P	0.997

dbSNP variants (sampled 300 via entrez): RS1000019411 (7:98200840 A>G), RS1000020941 (7:98132352 G>A), RS1000021967 (7:98165072 G>A), RS1000028315 (7:98209439 C>T), RS1000078448 (7:98156021 GAAAA>G,GA,GAAA,GAAAAA), RS1000099056 (7:98124246 G>A), RS1000131046 (7:98136403 A>C), RS1000147924 (7:98147705 C>T), RS1000158710 (7:98181776 A>C,G), RS1000169130 (7:98198481 G>A), RS1000183785 (7:98118859 G>A), RS1000184616 (7:98155497 A>G), RS1000216356 (7:98118596 C>T), RS1000273762 (7:98181480 A>G), RS1000284405 (7:98153738 C>T)

Disease associations

OMIM: gene MIM:610989 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000152_1	Prostate cancer	1.000000e-09
GCST006019_31	Gamma glutamyl transferase levels	4.000000e-12
GCST010083_147	Hemoglobin levels	1.000000e-13
GCST011320_16	Type 2 diabetes or prostate cancer (pleiotropy)	8.000000e-09
GCST011349_9	Gamma glutamyl transferase levels	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067300 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XVIII RTKs: LMR family

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
5.62	Kd	2395	nM	CHEMBL3752910
5.62	ED50	2395	nM	CHEMBL3752910

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149880: Binding affinity to human LMTK2 incubated for 45 mins by Kinobead based pull down assay	kd	2.3948	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases expression, increases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Temozolomide	affects response to substance	1
Leflunomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases methylation, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Carmustine	affects response to substance	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Disulfiram	affects binding, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Thiram	increases expression	1
Urethane	increases expression	1
Metals, Heavy	decreases methylation, increases abundance	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases 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
CHEMBL5652922	Binding	Binding affinity to human LMTK2 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SV72	HAP1 LMTK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer