PTK7

Chr 6

protein tyrosine kinase 7 (inactive)

Also known as: CCK-4, CCK4

NCBI Gene: 5754ENSG00000112655UniProt: Q13308OMIM: 601890

This protein is an inactive receptor tyrosine kinase that functions in Wnt signaling pathways and regulates cell adhesion, migration, polarity, and cytoskeletal organization during embryonic development and tissue formation. Mutations cause neurodevelopmental disorders with intellectual disability and structural brain abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not well tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.28
Clinical Summary— PTK7
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 114 VUS of 187 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.997
Z-score 5.69
OE 0.15 (0.09–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.24Z-score
OE missense 0.76 (0.70–0.81)
508 obs / 671.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.09–0.28)
0≤0.351.4
Missense OE0.76 (0.70–0.81)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 8 / 52.5Missense obs/exp: 508 / 671.4Syn Z: -0.55
DN
0.3594th %ile
GOF
0.4875th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

187 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS114
Likely Benign14
Benign14
9
Pathogenic
114
VUS
14
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
110
3
1
114
Likely Benign
0
10
0
4
14
Benign
0
4
3
7
14
Total01241512151

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PTK7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors.
Maitland ML et al.·Clin Cancer Res
2021
Click-constructed modular signal aptamer chimeras enable receptor-independent degradation of membrane proteins.
Xie W et al.·Proc Natl Acad Sci U S A
2025
The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation.
Lehmann J et al.·Signal Transduct Target Ther
2025
MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors.
Kong C et al.·Mol Cancer Ther
2023
Recent insights into the therapeutic strategies targeting the pseudokinase PTK7 in cancer.
Dessaux C et al.·Oncogene
2024Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients