PTK2

Chr 8

protein tyrosine kinase 2

Also known as: FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71, p125FAK, pp125FAK

NCBI Gene: 5747 ENSG00000169398 UniProt: Q05397 OMIM: 600758

This gene encodes focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase that regulates cell migration, adhesion, cytoskeletal organization, and is required for normal embryonic development including heart and nervous system development. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, seizures, and congenital heart defects. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.24), reflecting its essential role in development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.24

Clinical Summary— PTK2

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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.

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ClinVar Variants

92 VUS of 172 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.24LOEUF

pLI 1.000

Z-score 6.62

OE 0.14 (0.09–0.24)

Highly constrained

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

Missense Constraint?

3.44Z-score

OE missense 0.60 (0.55–0.66)

358 obs / 593.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.14 (0.09–0.24)

0≤0.351.4

Missense OE?0.60 (0.55–0.66)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 10 / 69.7Missense obs/exp: 358 / 593.7Syn Z: -0.37

This gene — mechanism propensity

0.4983th %ile

GOF

0.6247th %ile

LOF

0.64top 25%

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

LOFprediction above median · LOEUF 0.24

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

172 submitted variants in ClinVar

ClinVar

Classification Summary

VUS92

Likely Benign12

Benign10

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	91	0	0	92
Likely Benign	0	1	0	11	12
Benign	0	0	2	8	10
Conflicting	—				1
Total	1	92	2	19	115

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

View in ClinVar →

54 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap PTK2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →