PBXIP1

Chr 1

PBX homeobox interacting protein 1

Also known as: HPIP

The protein encoded by this gene interacts with the PBX1 homeodomain protein, inhibiting its transcriptional activation potential by preventing its binding to DNA. The encoded protein, which is primarily cytosolic but can shuttle to the nucleus, also can interact with estrogen receptors alpha and beta and promote the proliferation of breast cancer, brain tumors, and lung cancer. Several transcript variants encoding different isoforms have been found for this gene. More variants exist, but their full-length natures have yet to be determined. [provided by RefSeq, Dec 2015]

ResearchGenerating clinical summary…
DNmechanismLOEUF 0.92
Clinical SummaryPBXIP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
107 VUS of 139 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.92LOEUF
pLI 0.000
Z-score 1.91
OE 0.64 (0.450.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.79Z-score
OE missense 0.89 (0.810.97)
363 obs / 408.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.64 (0.450.92)
00.351.4
Missense OE?0.89 (0.810.97)
00.61.4
Synonymous OE?0.87
01.21.6
LoF obs/exp: 21 / 32.8Missense obs/exp: 363 / 408.1Syn Z: 1.31

This gene — mechanism propensity

DN
0.6357th %ile
GOF
0.6053th %ile
LOF
0.3745th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

139 submitted variants in ClinVar

Classification Summary

VUS107
Likely Benign8
107
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
107
0
0
107
Likely Benign
0
5
0
3
8
Benign
0
0
0
0
0
Total011203115

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap PBXIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PBXIP1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →