TLK2

Chr 17AD

tousled like kinase 2

Also known as: HsHPK, MRD57, PKU-ALPHA

NCBI Gene: 11011 ENSG00000146872 UniProt: Q86UE8 OMIM: 608439

This gene encodes a nuclear serine/threonine kinase that phosphorylates chromatin assembly factors and regulates chromatin assembly during S phase of the cell cycle, DNA repair, and autophagy. Mutations cause autosomal dominant intellectual developmental disorder. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.11), indicating intolerance to disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nuclear serine/threonine kinase that was first identified in Arabidopsis. The encoded protein is thought to function in the regulation of chromatin assembly in the S phase of the cell cycle by regulating the levels of a histone H3/H4 chaperone. This protein is associated with double-strand break repair of DNA damage caused by radiation. Pseudogenes of this gene are present on chromosomes 10 and 17. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 57MIM #618050

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.11

LOEUF· LoF intol.

LOF

Mechanism· G2P