PTK7

Summary

PTK7 (protein tyrosine kinase 7 (inactive), HGNC:9618) is a protein-coding gene on chromosome 6p21.1, encoding Inactive tyrosine-protein kinase 7 (Q13308). Inactive tyrosine kinase involved in Wnt signaling pathway.

This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5754 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 170 total
• MANE Select transcript: NM_002821

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9618
Approved symbol	PTK7
Name	protein tyrosine kinase 7 (inactive)
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	CCK4
Ensembl gene	ENSG00000112655
Ensembl biotype	protein_coding
OMIM	601890
Entrez	5754

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 23 protein_coding, 6 nonsense_mediated_decay, 4 retained_intron

ENST00000230418, ENST00000230419, ENST00000345201, ENST00000349241, ENST00000352931, ENST00000461100, ENST00000461389, ENST00000470019, ENST00000470471, ENST00000471863, ENST00000473339, ENST00000476760, ENST00000481273, ENST00000481946, ENST00000487673, ENST00000489707, ENST00000490710, ENST00000493339, ENST00000494146, ENST00000497957, ENST00000886108, ENST00000886109, ENST00000886110, ENST00000930014, ENST00000930015, ENST00000930016, ENST00000930017, ENST00000930018, ENST00000930019, ENST00000930020, ENST00000930021, ENST00000971485, ENST00000971486

RefSeq mRNA: 5 — MANE Select: NM_002821 NM_001270398, NM_002821, NM_152880, NM_152881, NM_152882

CCDS: CCDS4884, CCDS4885, CCDS4886, CCDS4887, CCDS59021

Canonical transcript exons

ENST00000230419 — 20 exons

Exon	Start	End
ENSE00001935874	43076314	43076567
ENSE00003504059	43146618	43146698
ENSE00003504218	43144451	43144606
ENSE00003505291	43142172	43142299
ENSE00003506717	43128977	43129264
ENSE00003518178	43141668	43141817
ENSE00003526883	43159788	43159966
ENSE00003540994	43158817	43158968
ENSE00003563004	43141931	43142081
ENSE00003563580	43130230	43130420
ENSE00003567624	43139406	43139525
ENSE00003576641	43145200	43145432
ENSE00003587075	43132016	43132164
ENSE00003616797	43139136	43139271
ENSE00003620665	43130511	43130661
ENSE00003661453	43143417	43143620
ENSE00003665383	43129727	43129829
ENSE00003690274	43132421	43132687
ENSE00003693095	43138849	43138982
ENSE00003851109	43160721	43161715

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0169 / max 410.3239, expressed in 1514 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67858	26.2934	1486
67862	1.5413	947
67861	1.5169	926
67859	0.5838	378
67860	0.5446	372
67865	0.4859	253
67866	0.3853	173
203998	0.3508	207
67864	0.1199	38
67868	0.1088	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.36	gold quality
body of uterus	UBERON:0009853	97.24	gold quality
left ovary	UBERON:0002119	96.32	gold quality
right ovary	UBERON:0002118	96.29	gold quality
endocervix	UBERON:0000458	94.57	gold quality
ectocervix	UBERON:0012249	94.43	gold quality
right uterine tube	UBERON:0001302	93.99	gold quality
left uterine tube	UBERON:0001303	93.66	gold quality
right testis	UBERON:0004534	93.55	gold quality
left testis	UBERON:0004533	93.36	gold quality
ventricular zone	UBERON:0003053	93.18	gold quality
ovary	UBERON:0000992	92.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.17	gold quality
ganglionic eminence	UBERON:0004023	92.07	gold quality
upper lobe of left lung	UBERON:0008952	91.97	gold quality
metanephros cortex	UBERON:0010533	91.94	gold quality
embryo	UBERON:0000922	91.70	gold quality
skin of abdomen	UBERON:0001416	91.69	gold quality
corpus epididymis	UBERON:0004359	91.64	gold quality
myometrium	UBERON:0001296	91.61	gold quality
lower esophagus mucosa	UBERON:0035834	91.11	gold quality
right lung	UBERON:0002167	90.99	gold quality
upper lobe of lung	UBERON:0008948	90.95	gold quality
skin of leg	UBERON:0001511	90.85	gold quality
minor salivary gland	UBERON:0001830	90.70	gold quality
gall bladder	UBERON:0002110	90.36	gold quality
testis	UBERON:0000473	90.31	gold quality
uterus	UBERON:0000995	90.22	gold quality
adenohypophysis	UBERON:0002196	90.14	gold quality
right lobe of thyroid gland	UBERON:0001119	89.92	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	118.93
E-ANND-3	yes	9.67
E-MTAB-6678	yes	4.55
E-GEOD-124858	no	51.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, SP1

miRNA regulators (miRDB)

37 targeting PTK7, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4275	97.96	68.42	1549

Literature-anchored findings (GeneRIF, showing 40)

• cloning, sequencing and expression of gene and its splice variants (PMID:12427550)
• Lack of a thermodynamically meaningful self-association propensity for the CCK4 transmembrane domains demonstrates that the conserved GxxxG motif is not sufficient to drive CCK4 transmembrane helix-helix interactions. (PMID:15683231)
• mechanism of PTK7 upregulation in colorectal cancer (PMID:17671748)
• PTK7 plays an important role not only in tube formation, migration, and invasion of endothelial cells but also in angiogenesis. (PMID:18471990)
• PTK7 is a planar cell polarity component expressed in the myeloid progenitor compartment that conveys promigratory and antiapoptotic signals into the cell and represents an independent prognosis factor in patients treated with induction chemotherapy. (PMID:20558616)
• Results indicate that PTK7 is a major target of MT1-MMP. (PMID:20837484)
• Observations may indicate a role for PTK7 in cell proliferation and cell apoptosis and may provide a potential therapeutic pathway for the treatment of a variety of cancers. (PMID:21103379)
• Protein Tyrosine Kinase 7 is required for beta-catenin-dependent transcriptional events induced by canonical Wnt ligands (PMID:21132015)
• aberrations in the membrane type 1 matrix metalloproteinase/PTK7 axis are detrimental to cell movements that shape the body plan (PMID:21518755)
• a novel role for PTK7 in the tumorigenesis via generation of PTK7-CTF2 by sequential cleavage of ADAM17 and gamma-secretase. (PMID:22665490)
• PTK7 has utility as a biomarker for detecting minimal residual disease of T cell acute lymphoblastic leukemia in the bone marrow (PMID:22898210)
• cleavage of the PTK7 ectodomain by an ADAM proteinase was coupled with the membrane type-1 matrix metalloproteinase (MT1-MMP) cleavage of the PKP(621) downward arrowLI site in the seventh Ig-like domain of PTK7. (PMID:23095747)
• PTK7 is a novel marker of epithelial to mesenchymal transitions (PMID:23209741)
• Increased expression of PTK7 was inversely correlated with overall survival. (PMID:23663482)
• in patients treated by chemotherapy, patients with PTK7-negative tumors seemed to have better DFS than those with PTK7-positive tumors, particularly for patients treated with only anthracycline-therapy drugs (PMID:24023307)
• PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement. (PMID:24409301)
• PTK7 expression plays an important role in the invasiveness of intrahepatic cholangiocarcinoma (ICC) cells and leads to a poor prognosis in ICC patients. (PMID:24587299)
• This work defines PTK7 as a highly and specifically expressed gene in adenocarcinoma and a potential therapeutic target in this subset of NSCLC. (PMID:24654231)
• The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive prostate cancer (PMID:24741114)
• Furthermore, we confirmed that these phenotypic changes are associated with the inactivation of AKT and ERK. Our findings suggest that PTK7 has different oncogenic roles in organs and target tumors. (PMID:24789704)
• results provide convincing evidence that both PTK7 expression and proteolysis, rather than the level of the cellular full-length PTK7 alone, contribute to efficient directional cell motility and metastasis in cancer (PMID:25006253)
• PTK7 regulates Id1 expression in CD44-high glioma cell lines. Targeting PTK7 could be an effective strategy for treating glioma with high CD44 expression. (PMID:25204555)
• Expression level of PTK7 was significantly decreased from benign to malignant ovarian epithelial tumors. survival analysis showed that patients with negative expression of PTK7 protein had poorer outcome than those with positive expression. (PMID:25550828)
• PTK7 acts as a cancer-related gene and may be a potent prognostic marker for Hepatocellular carcinoma(HCC). (PMID:25796105)
• overexpression in PTK7-negative cancer cells led to increased metastatic events. PTK7 expression thus represents a potential prognostic biomarker and a novel therapeutic target in CRC. (PMID:25962058)
• data demonstrates that PTK7 regulates the activity of KDR biphasically by inducing oligomerization of KDR molecules at lower concentrations and by surrounding KDR molecules at higher concentrations. (PMID:25986862)
• findings implicate PTK7 as a risk factor for NTDs and provide additional evidence for a pathogenic role of PCP signaling in these malformations (PMID:26368655)
• PTK7 enriches in self-renewing, multipotent stem cells of the human colon. (PMID:26549850)
• PTK7 expression was correlated with tumor differentiation (P=0.027), lymph node metastasis (P=0.005), distant metastasis (P=0.001) and TNM stage (P=0.028) of colorectal cancer patients (PMID:27499181)
• High PTK7 expression is associated with radioresistance in esophageal squamous cell carcinoma. (PMID:27557627)
• These findings demonstrate that PTK7 upregulates MMP9 through activation of AP-1 and NF-kappaB and, thus increases invasive properties of ESCC cells. (PMID:27689325)
• PTK7 localization and protein stability is affected by canonical Wnt ligands. (PMID:28420671)
• Inhibition of PTK7 by siRNA treatment significantly decreases the viability of atypical teratoid rhabdoid tumors (ATRT)patient-derived tumor cell lines.These studies provide the groundwork for future preclinical in vivo studies aiming to investigate the efficacy of PTK7 inhibition on ATRT tumor growth (PMID:28442586)
• PTK7 overexpression is associated with esophageal squamous cell carcinoma. (PMID:28545451)
• Our data indicate that PTK7 protein expression is associated with the prognosis of oral tongue squamous cell carcinoma (PMID:28547980)
• Higher expression of PTK7 significantly indicates worse prognosis in human malignancies (PMID:28924970)
• miR2055p is involved in the proliferation, migration and invasion of colorectal cancer cells through inhibiting PTK7. (PMID:29488611)
• These results demonstrate that PTK7 biphasically regulates tumorigenesis in esophageal squamous cell carcinoma. (PMID:29867084)
• we report a novel strategy for obtaining ZnZr bimetallic MOFs via the MOF-on-MOF method and exploit them as an aptasensor platform for detecting the cancer marker protein tyrosine kinase-7 (PTK7) (PMID:30308421)
• Rare missense variants in PTK7 contribute to the genetic risk of spina bifida. (PMID:30689296)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptk7a	ENSDARG00000011863
danio_rerio		ENSDARG00000111743
mus_musculus	Ptk7	ENSMUSG00000023972
rattus_norvegicus	Ptk7	ENSRNOG00000039976
drosophila_melanogaster	otk	FBGN0004839
drosophila_melanogaster	otk2	FBGN0267728

Protein

Protein identifiers

Inactive tyrosine-protein kinase 7 — Q13308 (reviewed: Q13308)

Alternative names: Colon carcinoma kinase 4, Protein-tyrosine kinase 7, Pseudo tyrosine kinase receptor 7, Tyrosine-protein kinase-like 7

All UniProt accessions (10): Q13308, C9J9E8, C9JQR6, F8WCI7, F8WDG7, H0Y889, H0Y8F1, H7C4X3, H7C5L0, Q86X91

UniProt curated annotations — full annotation on UniProt →

Function. Inactive tyrosine kinase involved in Wnt signaling pathway. Component of both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathway. Functions in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization and apoptosis. Has a role in embryogenesis, epithelial tissue organization and angiogenesis.

Subunit / interactions. Interacts with CTNNB1.

Subcellular location. Membrane. Cell junction.

Tissue specificity. Highly expressed in lung, liver, pancreas, kidney, placenta and melanocytes. Weakly expressed in thyroid gland, ovary, brain, heart and skeletal muscle. Also expressed in erythroleukemia cells. But not expressed in colon.

Post-translational modifications. MMP14 cleaves PTK7 between Pro-621 and Leu-622 generating an N-terminal soluble (70 kDa) fragment and a membrane C-terminal (50 kDa) fragment. Proteolysis by MMP14 regulates PTK7 function in non-canonical Wnt signaling pathway.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Induction. Higher expression in cell lines established from normal non-tumorigenic tissues compared to cell lines established from highly metastatic invasive carcinomas (at protein level).

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q13308-1	1, PTK7-1	yes
Q13308-2	2, PTK7-2
Q13308-3	3, PTK7-3
Q13308-4	4, PTK7-4
Q13308-5	5, PTK7-5
Q13308-6	6

RefSeq proteins (5): NP_001257327, NP_002812, NP_690619, NP_690620, NP_690621 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050958	Cell_Adh-Cytoskel_Orgn	Family

Pfam: PF07679, PF07714, PF13927

UniProt features (90 total): helix 13, sequence conflict 12, glycosylation site 10, strand 10, sequence variant 9, domain 8, disulfide bond 7, splice variant 6, region of interest 3, mutagenesis site 3, topological domain 2, turn 2, signal peptide 1, chain 1, site 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6VG3	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13308-F1	83.15	0.49

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): 621–622 (cleavage; by mmp14)

Post-translational modifications (1): 1064

Disulfide bonds (7): 53–101, 150–200, 246–301, 343–391, 433–481, 524–570, 613–664

Glycosylation sites (10): 116, 175, 184, 214, 268, 283, 405, 463, 567, 646

Mutagenesis-validated functional residues (3):

Position	Phenotype
622	prevents proteolysis by mmp14.
641	no impact on proteolysis by mmp14.
701	no impact on proteolysis by mmp14.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 266 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BROWNE_HCMV_INFECTION_4HR_UP, MYAATNNNNNNNGGC_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, MODULE_451, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GOBP_GROWTH, AP4_Q6

GO Biological Process (25): establishment of planar polarity (GO:0001736), kidney development (GO:0001822), neural tube closure (GO:0001843), ventricular septum development (GO:0003281), axis elongation (GO:0003401), homophilic cell-cell adhesion (GO:0007156), signal transduction (GO:0007165), positive regulation of neuron projection development (GO:0010976), Wnt signaling pathway (GO:0016055), cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), wound healing (GO:0042060), establishment of epithelial cell apical/basal polarity (GO:0045198), synapse organization (GO:0050808), convergent extension (GO:0060026), lung-associated mesenchyme development (GO:0060484), regulation of canonical Wnt signaling pathway (GO:0060828), coronary vasculature development (GO:0060976), cellular response to retinoic acid (GO:0071300), cochlea morphogenesis (GO:0090103), positive regulation of canonical Wnt signaling pathway (GO:0090263), protein phosphorylation (GO:0006468), cell adhesion (GO:0007155), axon guidance (GO:0007411), heart development (GO:0007507)

GO Molecular Function (7): protein kinase activity (GO:0004672), ATP binding (GO:0005524), axon guidance receptor activity (GO:0008046), coreceptor activity (GO:0015026), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), axon (GO:0030424), neuronal cell body (GO:0043025), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
morphogenesis of a polarized epithelium	1
establishment of tissue polarity	1
animal organ development	1
renal system development	1
primary neural tube formation	1
tube closure	1
cardiac ventricle development	1
cardiac septum development	1
developmental growth involved in morphogenesis	1
cell-cell adhesion	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cell surface receptor signaling pathway	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
response to wounding	1
tissue regeneration	1
polarized epithelial cell differentiation	1
establishment of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
establishment of epithelial cell polarity	1
cell junction organization	1
morphogenesis of an epithelium	1
lung development	1
mesenchyme development	1
regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
blood vessel development	1
heart development	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1

Protein interactions and networks

STRING

3810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTK7	WNT5A	P41221	981
PTK7	CCKAR	P32238	950
PTK7	CCKBR	P32239	934
PTK7	CCK	P06307	923
PTK7	VANGL2	Q9ULK5	887
PTK7	VANGL1	Q8TAA9	879
PTK7	DVL1	O14640	860
PTK7	WNT3A	P56704	854
PTK7	POSTN	Q15063	812
PTK7	LRP6	O75581	807
PTK7	CELSR1	Q9NYQ6	764
PTK7	WNT4	P56705	764
PTK7	FZD6	O60353	720
PTK7	LRP5	O75197	701
PTK7	DACT1	Q9NYF0	694

IntAct

149 interactions, top by confidence:

A	B	Type	Score
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
CTNNB1	PTK7	psi-mi:“MI:0915”(physical association)	0.580
PTK7	CTNNB1	psi-mi:“MI:0915”(physical association)	0.580
NOTCH2NLC	PTK7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	PTK7	psi-mi:“MI:0915”(physical association)	0.560
PTK7	MDFI	psi-mi:“MI:0915”(physical association)	0.560
PTK7	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	PTK7	psi-mi:“MI:0915”(physical association)	0.560
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
PTK7	CLNK	psi-mi:“MI:0915”(physical association)	0.490
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
PTK7	NCL	psi-mi:“MI:0915”(physical association)	0.400
PTK7	SEMG1	psi-mi:“MI:0915”(physical association)	0.400
PTK7	SUB1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (195): PTK7 (Affinity Capture-MS), PTK7 (Affinity Capture-MS), PTK7 (Affinity Capture-MS), PTK7 (Affinity Capture-MS), PTK7 (Affinity Capture-MS), PPM1G (Co-fractionation), PTK7 (Two-hybrid), PTK7 (Proximity Label-MS), PPP3CA (Two-hybrid), PPP3CB (Two-hybrid), PPM1A (Two-hybrid), PPM1B (Two-hybrid), PPM1F (Two-hybrid), PPM1K (Two-hybrid), ILKAP (Two-hybrid)

ESM2 similar proteins: A2AAJ9, A2ABU4, A2RUH7, B4GBH0, D3ZGQ5, O09127, O70468, O75038, O88599, O95382, P16419, P21709, P22455, P22607, P29322, P54760, P54761, P55144, P55146, P56741, P70218, P70402, Q00653, Q06418, Q13203, Q13308, Q13425, Q14896, Q15746, Q290N5, Q32P44, Q4LDD4, Q5FW53, Q5PQM4, Q5VST9, Q5VTT5, Q60750, Q61851, Q68LP1, Q80UW5

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RACK1	up-regulates	PTK7	binding
PTK7	down-regulates	CTNNB1	binding
SRC	“up-regulates activity”	PTK7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
FRS-mediated FGFR4 signaling	5	22.2×	2e-04
SHC1 events in ERBB2 signaling	5	21.2×	2e-04
Downstream signal transduction	5	17.0×	4e-04
Negative regulation of MAPK pathway	7	16.6×	3e-05
Signaling by high-kinase activity BRAF mutants	5	14.2×	7e-04
R-HSA-425366	8	12.9×	3e-05
MAP2K and MAPK activation	5	12.8×	1e-03
NCAM signaling for neurite out-growth	5	12.1×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine dephosphorylation	5	31.4×	2e-04
dephosphorylation	6	28.7×	3e-05
obsolete organic anion transport	5	28.5×	2e-04
protein dephosphorylation	15	23.6×	7e-14
peptidyl-tyrosine phosphorylation	5	14.9×	2e-03
amino acid transport	6	13.3×	7e-04
negative regulation of MAPK cascade	5	10.7×	6e-03
transport across blood-brain barrier	8	10.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	13
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

3161 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43128970:T:G	acceptor_gain	1.0000
6:43128974:CAGG:C	acceptor_loss	1.0000
6:43128975:A:AG	acceptor_gain	1.0000
6:43128976:G:GA	acceptor_loss	1.0000
6:43128976:G:GG	acceptor_gain	1.0000
6:43129261:AAATG:A	donor_loss	1.0000
6:43129262:AATGT:A	donor_loss	1.0000
6:43129263:AT:A	donor_gain	1.0000
6:43129264:TGTG:T	donor_loss	1.0000
6:43129265:G:GG	donor_gain	1.0000
6:43129265:GTGA:G	donor_loss	1.0000
6:43129266:T:G	donor_loss	1.0000
6:43130658:GTCG:G	donor_gain	1.0000
6:43132014:A:AG	acceptor_gain	1.0000
6:43132015:G:GG	acceptor_gain	1.0000
6:43132410:T:G	acceptor_gain	1.0000
6:43132419:A:AG	acceptor_gain	1.0000
6:43132420:G:GG	acceptor_gain	1.0000
6:43132666:G:GT	donor_gain	1.0000
6:43132683:GGCC:G	donor_gain	1.0000
6:43132688:G:GG	donor_gain	1.0000
6:43138838:T:TA	acceptor_gain	1.0000
6:43138842:T:TA	acceptor_gain	1.0000
6:43138844:TCTA:T	acceptor_loss	1.0000
6:43138845:CTA:C	acceptor_loss	1.0000
6:43138846:TAGCT:T	acceptor_loss	1.0000
6:43138847:A:AG	acceptor_gain	1.0000
6:43138847:AGCT:A	acceptor_gain	1.0000
6:43138848:G:A	acceptor_loss	1.0000
6:43138848:G:GA	acceptor_gain	1.0000

AlphaMissense

6997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43138953:T:A	W445R	1.000
6:43138953:T:C	W445R	1.000
6:43139418:T:C	F504S	1.000
6:43139513:T:A	W536R	1.000
6:43139513:T:C	W536R	1.000
6:43139515:G:C	W536C	1.000
6:43139515:G:T	W536C	1.000
6:43141757:T:C	C570R	1.000
6:43141764:C:A	A572D	1.000
6:43142035:T:A	W625R	1.000
6:43142035:T:C	W625R	1.000
6:43142036:G:C	W625S	1.000
6:43142037:G:C	W625C	1.000
6:43142037:G:T	W625C	1.000
6:43142198:T:C	L649P	1.000
6:43130243:T:A	W162R	0.999
6:43130243:T:C	W162R	0.999
6:43130245:G:C	W162C	0.999
6:43130245:G:T	W162C	0.999
6:43130621:T:A	W258R	0.999
6:43130621:T:C	W258R	0.999
6:43130623:G:C	W258C	0.999
6:43130623:G:T	W258C	0.999
6:43132098:T:G	Y299D	0.999
6:43132527:G:C	W356C	0.999
6:43132527:G:T	W356C	0.999
6:43138955:G:C	W445C	0.999
6:43138955:G:T	W445C	0.999
6:43139170:T:C	L466S	0.999
6:43139208:T:G	Y479D	0.999

dbSNP variants (sampled 300 via entrez): RS1000016969 (6:43114906 G>T), RS1000026213 (6:43116936 G>C), RS1000078234 (6:43146834 A>C,G), RS1000088647 (6:43115248 C>G), RS1000139289 (6:43123126 A>T), RS1000169639 (6:43080897 G>A), RS1000193418 (6:43122814 C>T), RS1000287664 (6:43151211 C>T), RS1000318329 (6:43132252 C>G), RS1000345903 (6:43102250 C>A), RS1000376987 (6:43086335 C>A), RS1000378913 (6:43144201 T>A,C,G), RS1000400096 (6:43128513 G>C,T), RS1000433739 (6:43138297 C>A,T), RS1000464631 (6:43156064 A>G)

Disease associations

OMIM: gene MIM:601890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005194_91	Coronary artery disease	6.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type VI RTKs: PTK7/CCK4

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
bisphenol A	increases expression, affects expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	increases expression, decreases expression	2
tremortin	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
celastrol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
seocalcitol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Benztropine	decreases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Cisplatin	affects cotreatment, increases expression	1
Bucladesine	affects cotreatment, increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6BB	HyCyte HCT 116 KO-hPTK7	Cancer cell line	Male
CVCL_E0M9	Ubigene HeLa PTK7 KO	Cancer cell line	Female
CVCL_TH55	HAP1 PTK7 (-) 1	Cancer cell line	Male
CVCL_TH56	HAP1 PTK7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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