DSTYK

Chr 1ADAR

dual serine/threonine and tyrosine protein kinase

Also known as: CAKUT1, DustyPK, HDCMD38P, RHDNS1, RIP5, RIPK5, SPG23

NCBI Gene: 25778 ENSG00000133059 UniProt: Q6XUX3 OMIM: 612666

This dual serine/threonine and tyrosine protein kinase acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor receptor activation and regulates both caspase-dependent apoptosis and caspase-independent cell death pathways. Mutations cause autosomal recessive spastic paraplegia 23 and congenital anomalies of kidney and urinary tract, as well as autosomal dominant forms of renal and urinary tract malformations. The gene shows significant constraint against loss-of-function variants (LOEUF 0.37), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. It is thought to function as a regulator of cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital anomalies of kidney and urinary tract 1MIM #610805

Spastic paraplegia 23, autosomal recessiveMIM #270750

Clinical highlights

Gene-disease validity (ClinGen)

complex hereditary spastic paraplegia · ARModerateconsider for supplementary testing

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)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

LOF

Mechanism· G2P