PTK6

Chr 20

protein tyrosine kinase 6

Also known as: BRK

NCBI Gene: 5753ENSG00000101213UniProt: Q13882

The protein encoded by this gene is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. The encoded protein has been shown to undergo autophosphorylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

166
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PTK6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 105 VUS of 166 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.34LOEUF
pLI 0.000
Z-score 0.33
OE 0.92 (0.65–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.39Z-score
OE missense 0.93 (0.85–1.03)
270 obs / 288.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.92 (0.65–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.85–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 20 / 21.7Missense obs/exp: 270 / 288.8Syn Z: -0.76

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic9
VUS105
Likely Benign3
Benign1
Conflicting2
46
Pathogenic
9
Likely Pathogenic
105
VUS
3
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
9
0
9
VUS
0
79
26
0
105
Likely Benign
0
2
0
1
3
Benign
0
1
0
0
1
Conflicting
—2
Total082811166

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

View in ClinVar →

Protein Context — Lollipop Plot

PTK6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer.
Dai LJ et al.·Nat Commun
2023Cohort
Kinase-Dependent and -Independent Roles for PTK6 in Colon Cancer.
Mathur PS et al.·Mol Cancer Res
2016
Comprehensive Analysis Reveals PTK6 as a Prognostic Biomarker Involved in the Immunosuppressive Microenvironment in Breast Cancer.
Wang L et al.·J Immunol Res
2022
High heterogeneity of cross-reactive immunoglobulins in multiple sclerosis presumes combining of B-cell epitopes for diagnostics: a case-control study.
Ovchinnikova LA et al.·Front Immunol
2024
PTK6 activation at the membrane regulates epithelial-mesenchymal transition in prostate cancer.
Zheng Y et al.·Cancer Res
2013
Downregulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma.
Chen YF et al.·Med Oncol
2014
PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation.
Ito K et al.·Cancer Res
2016
Pharmacological targeting PTK6 inhibits the JAK2/STAT3 sustained stemness and reverses chemoresistance of colorectal cancer.
Liu C et al.·J Exp Clin Cancer Res
2021
The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of β-catenin.
Brauer PM et al.·PLoS One
2011
Prognosis-related autophagy genes in female lung adenocarcinoma.
Liu Z et al.·Medicine (Baltimore)
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Liver cancer-derived exosomal PTK6 induces the secretion of pulmonary CHI3L1 to facilitate lung metastatic niche formation.
Yang J et al.·Cancer Lett
2026
PTK6 mediated immune signatures revealed by single cell transcriptomic and multi omics big data analysis in cervical cancer.
Zhao F et al.·Discov Oncol
2025🔓 Open Access
Bioinformatics-based prognostic value and in vitro functional validation of PTK6 in cutaneous melanoma.
Niu Y et al.·Front Oncol
2025🔓 Open AccessFunctional
Multi-gene anoikis signature combined with tumor microenvironment stratifies prognosis in cutaneous melanoma with experimental validation of PTK6.
Lin J et al.·Gene
2025
Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma.
Liang L et al.·Discov Oncol
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools