PTK6

Chr 20

protein tyrosine kinase 6

Also known as: BRK

NCBI Gene: 5753 ENSG00000101213 UniProt: Q13882 OMIM: 602004

The protein encoded by this gene is a cytoplasmic non-receptor tyrosine kinase that regulates epithelial cell differentiation, maintenance, and signaling pathways including EGFR, STAT3/5, and various RNA-binding proteins. This gene is extremely intolerant to loss-of-function variants in the general population, but no Mendelian pediatric neurogenetic disorders have been established from mutations in PTK6 based on current evidence. The gene's primary known associations are with epithelial biology and cancer rather than inherited neurological conditions.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.34

Clinical Summary— PTK6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

79 VUS of 91 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.39Z-score

OE missense 0.93 (0.85–1.03)

270 obs / 288.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.65–1.34)

0≤0.351.4

Missense OE?0.93 (0.85–1.03)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 20 / 21.7Missense obs/exp: 270 / 288.8Syn Z: -0.76

This gene — mechanism propensity

0.6745th %ile

GOF

0.74top 25%

LOF

0.3164th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

VUS79

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	79	0	79
Likely Benign	2	1	3
Benign	1	0	1
Total	82	1	83

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 84) ClinVar copy-number / structural variants overlap PTK6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →