PTPRCAP

Chr 11

protein tyrosine phosphatase receptor type C associated protein

Also known as: CD45-AP, LPAP

NCBI Gene: 5790 ENSG00000213402 UniProt: Q14761

The protein is a transmembrane phosphoprotein that associates with the tyrosine phosphatase CD45, which regulates T- and B-lymphocyte activation in the immune system. Mutations in PTPRCAP cause autosomal recessive combined immunodeficiency characterized by severe infections and immune dysfunction typically presenting in infancy. The gene shows moderate constraint against loss-of-function variants, consistent with its role in essential immune cell signaling pathways.

ResearchSummary from RefSeq

The protein encoded by this gene was identified as a transmembrane phosphoprotein specifically associated with tyrosine phosphatase PTPRC/CD45, a key regulator of T- and B-lymphocyte activation. The interaction with PTPRC may be required for the stable expression of this protein. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.23

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.23LOEUF

pLI 0.540

Z-score 1.41

OE 0.00 (0.00–1.23)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.30Z-score

OE missense 0.93 (0.80–1.08)

118 obs / 127.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.23)

0≤0.351.4

Missense OE?0.93 (0.80–1.08)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 2.3Missense obs/exp: 118 / 127.5Syn Z: -0.08

Background carrier burden — how many people carry a rare variant somewhere in PTPRCAP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

306 rare PASS variants

Rare truncating (LoF)

1 in 5,000

39 rare PASS variants

Rare synonymous (reference)

1 in 220

145 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PTPRCAP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 4,300
South Asian	~43k	1 in 95	1 in 1,900
Remaining (unassigned)	~30k	1 in 99	≈ 1 in 30,000
European (Finnish)	~27k	1 in 420	≈ 1 in 7,900
Admixed American	~22k	1 in 130	1 in 3,100
African / African American	~21k	1 in 150	none seen
East Asian	~20k	1 in 180	1 in 2,100
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓