PPFIA1

Chr 11

PPFI scaffold protein A1

Also known as: LIP.1, LIP1, LIPRIN

NCBI Gene: 8500ENSG00000131626UniProt: Q13136

The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

268
ClinVar variants
8
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PPFIA1
⚡
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.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 181 VUS of 268 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.07LOEUF
pLI 1.000
Z-score 7.69
OE 0.01 (0.00–0.07)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.06Z-score
OE missense 0.89 (0.83–0.95)
618 obs / 696.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.01 (0.00–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.83–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 1 / 70.8Missense obs/exp: 618 / 696.8Syn Z: 0.83

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS181
Likely Benign34
Benign10
6
Pathogenic
2
Likely Pathogenic
181
VUS
34
Likely Benign
10
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
178
3
0
181
Likely Benign
0
4
3
27
34
Benign
0
2
2
6
10
Total01841633233

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

View in ClinVar →

Protein Context — Lollipop Plot

PPFIA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PPFIA1 and CCND1 are frequently coamplified in breast cancer.
Dancau AM et al.·Genes Chromosomes Cancer
2010
PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer.
Alfarsi LH et al.·BMC Cancer
2020
Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast.
Choi EJ et al.·World J Surg Oncol
2014
VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma.
Miao H et al.·Hum Cell
2024
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma.
Gregory-Evans CY et al.·Hum Mol Genet
2007
Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations.
Schluth-Bolard C et al.·J Med Genet
2013Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
From resistance to sensitivity: the impact of FADD and lncRNA PPFIA1-AS1 on cisplatin treatment in LUSC.
Chang X et al.·Cancer Gene Ther
2026
Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report.
Yan L et al.·Front Oncol
2023🔓 Open AccessCase report
High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis.
Gao Y et al.·BMC Cancer
2023🔓 Open Access
PPFIA1-targeting miR-181a mimic and saRNA overcome imatinib resistance in BCR-ABL1-independent chronic myeloid leukemia by suppressing leukemia stem cell regeneration.
Su R et al.·Mol Ther Nucleic Acids
2023🔓 Open Access
High PPFIA1 expression promotes cancer survival by suppressing CD8+ T cells in breast cancer: drug discovery and machine learning approach.
Chu J et al.·Breast Cancer
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools