PTPN23

Chr 3

protein tyrosine phosphatase non-receptor type 23

The protein tyrosine phosphatase PTPN23 functions in endosomal cargo sorting via ESCRT complexes and plays a role in ciliogenesis and regulation of the survival motor neuron complex involved in pre-mRNA splicing. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with structural brain anomalies, with or without seizures and spasticity. The gene shows high constraint against loss-of-function variants (LOEUF 0.372), reflecting its essential cellular functions.

ResearchSummary from RefSeq, OMIM, UniProt

Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes (PubMed:18434552, PubMed:21757351). May act as a negative regulator of Ras-mediated mitogenic activity (PubMed:18434552). Plays a role in ciliogenesis (PubMed:20393563)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity

Clinical highlights

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

Some data sources returned errors (2)

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