PTPN20

Chr 10

protein tyrosine phosphatase non-receptor type 20

Also known as: CT126, PTPN20A, PTPN20B, bA142I17.1, bA42B19.1

The protein is a tyrosine-specific protein phosphatase that targets sites of actin polymerization and dephosphorylates various tyrosyl phosphorylated substrates in response to extracellular stimuli. Based on available data, no definitive disease associations or inheritance patterns have been established for PTPN20 mutations in pediatric neurological disorders. The gene shows low constraint against loss-of-function variants, suggesting it may tolerate such changes without causing severe developmental phenotypes.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
51
P/LP submissions
P/LP missense
1.93
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPTPN20
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 23 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.016
Z-score -0.61
OE 1.59 (0.471.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.55Z-score
OE missense 0.47 (0.231.07)
4 obs / 8.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.59 (0.471.93)
00.351.4
Missense OE0.47 (0.231.07)
00.61.4
Synonymous OE0.29
01.21.6
LoF obs/exp: 2 / 1.3Missense obs/exp: 4 / 8.6Syn Z: 1.04
DN
0.6842th %ile
GOF
0.73top 25%
LOF
0.2483th %ile

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

GOFprediction above median
DNprediction 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

117 submitted variants in ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic17
VUS23
Likely Benign3
Benign39
34
Pathogenic
17
Likely Pathogenic
23
VUS
3
Likely Benign
39
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
34
Likely Pathogenic
17
VUS
23
Likely Benign
3
Benign
39
Total116

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PTPN20 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC