PAXIP1

Chr 7

PAX interacting protein 1

Also known as: CAGF28, CAGF29, PACIP1, PAXIP1L, PTIP, TNRC2

NCBI Gene: 22976ENSG00000157212UniProt: Q6ZW49

This gene is a member of the paired box (PAX) gene family and encodes a nuclear protein with six BRCT (breast cancer carboxy-terminal) domains. This protein plays a critical role in maintaining genome stability, condensation of chromatin and progression through mitosis. [provided by RefSeq, Jul 2008]

173
ClinVar variants
75
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PAXIP1
⚡
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
75 Pathogenic / Likely Pathogenic· 89 VUS of 173 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.10LOEUF
pLI 1.000
Z-score 7.15
OE 0.03 (0.01–0.10)
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.
3.28Z-score
OE missense 0.61 (0.55–0.66)
332 obs / 548.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.03 (0.01–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.55–0.66)
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.0.89
0≤1.21.6
LoF obs/exp: 2 / 63.5Missense obs/exp: 332 / 548.3Syn Z: 1.29

ClinVar Variant Classifications

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic5
VUS89
Likely Benign9
70
Pathogenic
5
Likely Pathogenic
89
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
70
0
70
Likely Pathogenic
0
0
5
0
5
VUS
0
79
10
0
89
Likely Benign
0
5
0
4
9
Benign
0
0
0
0
0
Total084854173

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

View in ClinVar →

Protein Context — Lollipop Plot

PAXIP1 · 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
Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.
Harvey-Jones E et al.·Ann Oncol
2024Natural history
PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer.
Chen B et al.·PLoS One
2023
Allele-Specific Regulation of PAXIP1-AS1 by SMC3/CEBPB at rs112651172 in Psychiatric Disorders Drives Synaptic and Behavioral Dysfunctions in Mice.
Ni C et al.·Adv Sci (Weinh)
2025
Long non-coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1-AS1.
Jandl K et al.·J Pathol
2019
The impact of rare germline variants on human somatic mutation processes.
Vali-Pour M et al.·Nat Commun
2022
CELSR1 Risk Alleles in Familial Bicuspid Aortic Valve and Hypoplastic Left Heart Syndrome.
Theis JL et al.·Circ Genom Precis Med
2022
A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells.
Gasparini VR et al.·Blood Cancer J
2020
Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis.
Tsukada A et al.·Int J Mol Sci
2024Cohort
Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores.
Ishorst N et al.·Mol Genet Genomic Med
2023Cohort
A multiancestral genome-wide exome array study of Alzheimer disease, frontotemporal dementia, and progressive supranuclear palsy.
Chen JA et al.·JAMA Neurol
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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