PTPRF

Chr 1AR

protein tyrosine phosphatase receptor type F

Also known as: BNAH2, LAR

NCBI Gene: 5792 ENSG00000142949 UniProt: P10586 OMIM: 179590

The protein functions as a receptor-type protein tyrosine phosphatase that regulates cell-cell contacts at adherens junctions and controls beta-catenin signaling, while also dephosphorylating EPHA2 to regulate its activity. Mutations cause autosomal recessive aplasia or hypoplasia of breasts and/or nipples. This gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.187), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, 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 possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.191 OMIM phenotype

Clinical Summary— PTPRF

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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

2 unique Pathogenic / Likely Pathogenic· 256 VUS of 366 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 7.86

OE 0.11 (0.07–0.19)

Highly constrained

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

Missense Constraint?

2.80Z-score

OE missense 0.78 (0.74–0.82)

990 obs / 1270.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.11 (0.07–0.19)

0≤0.351.4

Missense OE?0.78 (0.74–0.82)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 10 / 90.8Missense obs/exp: 990 / 1270.4Syn Z: -0.60

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedPTPRF-related atheliaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4487th %ile

GOF

0.4875th %ile

LOF

0.65top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

366 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS256

Likely Benign49

Benign21

Pathogenic

Likely Pathogenic

256

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	1	0	0	0	1
VUS	0	256	0	0	256
Likely Benign	0	15	3	31	49
Benign	0	4	5	12	21
Total	2	275	8	43	328

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap PTPRF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →