PTP4A3

Chr 8

protein tyrosine phosphatase 4A3

Also known as: PRL-3, PRL-R, PRL3

The protein is a tyrosine phosphatase that regulates cell cycle progression from G1 to S phase and enhances cell proliferation and motility. Mutations cause autosomal recessive intellectual disability with neurodegeneration and brain atrophy, typically presenting in early childhood. The gene shows low constraint to loss-of-function variants, consistent with a recessive inheritance pattern.

Summary from RefSeq, UniProt
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0
Active trials
12
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.12
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPTP4A3
Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.12LOEUF
pLI 0.045
Z-score 1.38
OE 0.43 (0.201.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.06Z-score
OE missense 0.73 (0.620.87)
93 obs / 126.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.201.12)
00.351.4
Missense OE0.73 (0.620.87)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 3 / 6.9Missense obs/exp: 93 / 126.6Syn Z: 0.78
DN
0.76top 25%
GOF
0.73top 25%
LOF
0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTP4A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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