PTPRD

Chr 9

protein tyrosine phosphatase receptor type D

Also known as: HPTP, HPTPD, HPTPDELTA, PTPD, R-PTP-delta, RPTPDELTA

NCBI Gene: 5789 ENSG00000153707 UniProt: P23468 OMIM: 601598

This receptor-type protein tyrosine phosphatase regulates synaptic differentiation and neuronal axon guidance through trans-synaptic interactions. Mutations cause neurodevelopmental disorders with intellectual disability and restless legs syndrome, inherited in an autosomal dominant pattern. The gene is extremely constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

GeneReviews 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 region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 0.11

Clinical Summary— PTPRD

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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

221 VUS of 343 total submissions

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GeneReview available — PTPRD

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.11LOEUF

pLI 1.000

Z-score 8.52

OE 0.05 (0.03–0.11)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

0.27Z-score

OE missense 0.98 (0.93–1.03)

1058 obs / 1083.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.03–0.11)

0≤0.351.4

Missense OE?0.98 (0.93–1.03)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 5 / 94.2Missense obs/exp: 1058 / 1083.3Syn Z: -5.58

ClinVar Variant Classifications

343 submitted variants in ClinVar

ClinVar

Classification Summary

VUS221

Likely Benign45

Benign23

Conflicting2

221

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	220	0	0	221
Likely Benign	2	5	5	33	45
Benign	1	5	3	14	23
Conflicting	—				2
Total	4	230	8	47	291

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

View in ClinVar →

150 pathogenic / likely-pathogenic (of 216) ClinVar copy-number / structural variants overlap PTPRD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →