PTPRA

Chr 20

protein tyrosine phosphatase receptor type A

Also known as: HEPTP, HLPR, HPTPA, HPTPalpha, LRP, PTPA, PTPRL2, R-PTP-alpha

NCBI Gene: 5786 ENSG00000132670 UniProt: P18433 OMIM: 176884

The protein tyrosine phosphatase receptor type A (PTPRA) is a transmembrane enzyme that dephosphorylates and activates Src family tyrosine kinases, playing a critical role in integrin-mediated focal adhesion formation, cell adhesion, and proliferation. Mutations in this highly constrained gene (pLI=1.0, LOEUF=0.19) cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy. The condition primarily affects the central nervous system with severe intellectual disability, seizures, and brain malformations.

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. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. This PTP has been shown to dephosphorylate and activate Src family tyrosine kinases, and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.19

Clinical Summary— PTPRA

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 149 VUS of 202 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 5.87

OE 0.08 (0.04–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.67Z-score

OE missense 0.65 (0.59–0.72)

307 obs / 469.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.19)

0≤0.351.4

Missense OE?0.65 (0.59–0.72)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 4 / 47.7Missense obs/exp: 307 / 469.8Syn Z: 0.74

ClinVar Variant Classifications

202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic6

VUS149

Likely Benign9

Benign6

Conflicting1

Pathogenic

Likely Pathogenic

149

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	5	0	1	0	6
VUS	5	142	1	1	149
Likely Benign	0	4	0	5	9
Benign	0	1	2	3	6
Conflicting	—				1
Total	12	147	4	9	173

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

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25 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap PTPRA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →