PTPRE

Chr 10

protein tyrosine phosphatase receptor type E

Also known as: HPTPE, PTPE, R-PTP-EPSILON

NCBI Gene: 5791 ENSG00000132334 UniProt: P23469 OMIM: 600926

The protein encoded by PTPRE is a receptor-type protein tyrosine phosphatase that regulates cellular signaling pathways including RAS-related signal transduction, cytokine-induced STAT signaling, and activation of voltage-gated potassium channels. This gene is highly constrained against loss-of-function variants (pLI = 0.0008, LOEUF = 0.474), but associated diseases and inheritance patterns have not been established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Several alternatively spliced transcript variants of this gene have been reported, at least two of which encode a receptor-type PTP that possesses a short extracellular domain, a single transmembrane region, and two tandem intracytoplasmic catalytic domains; another one encodes a PTP that contains a distinct hydrophilic N-terminus, and thus represents a nonreceptor-type isoform of this PTP. Studies of the similar gene in mice suggested the regulatory roles of this PTP in RAS related signal transduction pathways, cytokine-induced SATA signaling, as well as the activation of voltage-gated K+ channels. [provided by RefSeq, Oct 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.47

Clinical Summary— PTPRE

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.001

Z-score 4.47

OE 0.31 (0.20–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.08Z-score

OE missense 0.72 (0.65–0.79)

310 obs / 431.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.31 (0.20–0.47)

0≤0.351.4

Missense OE?0.72 (0.65–0.79)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 15 / 48.7Missense obs/exp: 310 / 431.5Syn Z: 0.70

This gene — mechanism propensity

0.75top 25%

GOF

0.77top 25%

LOF

0.2190th %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.