PTPN23

Chr 3

protein tyrosine phosphatase non-receptor type 23

Also known as: HD-PTP, HDPTP, NEDBASS, PTP-TD14

NCBI Gene: 25930 ENSG00000076201 UniProt: Q9H3S7

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the non-receptor type protein-tyrosine phosphatase family. The encoded protein may be involved in the regulation of small nuclear ribonucleo protein assembly and pre-mRNA splicing by modifying the survival motor neuron (SMN) complex. The encoded protein additionally plays a role in ciliogenesis and is part of endosomal sorting complex required for transport (ESCRT) pathways. This gene may serve a tumor suppressor function. [provided by RefSeq, Jul 2016]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.37

Clinical Summary— PTPN23

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

54 unique Pathogenic / Likely Pathogenic· 740 VUS of 1611 total submissions

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GeneReview available — PTPN23

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.37LOEUF

pLI 0.031

Z-score 5.88

OE 0.25 (0.17–0.37)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.33Z-score

OE missense 0.88 (0.83–0.93)

872 obs / 989.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.17–0.37)

0≤0.351.4

Missense OE?0.88 (0.83–0.93)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 18 / 71.7Missense obs/exp: 872 / 989.8Syn Z: -1.75

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePTPN23-related neurodevelopmental disorder with or without structural brain anomalies, optic atrophy, seizures and spasticityLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6162th %ile

GOF

0.6247th %ile

LOF

0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

1611 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic20

VUS740

Likely Benign716

Benign42

Conflicting36

Pathogenic

Likely Pathogenic

740

VUS

716

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	31	2	1	0	34
Likely Pathogenic	18	2	0	0	20
VUS	20	685	33	2	740
Likely Benign	0	13	227	476	716
Benign	0	11	17	14	42
Conflicting	—				36
Total	69	713	278	492	1,588

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap PTPN23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →