PELP1

Chr 17

proline, glutamate and leucine rich protein 1

Also known as: MNAR, P160

NCBI Gene: 27043ENSG00000141456UniProt: Q8IZL8

This gene encodes a transcription factor which coactivates transcription of estrogen receptor responsive genes and corepresses genes activated by other hormone receptors or sequence-specific transcription factors. Expression of this gene is regulated by both members of the estrogen receptor family. This gene may be involved in the progression of several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

89
ClinVar variants
23
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PELP1
⚡
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
23 Pathogenic / Likely Pathogenic· 55 VUS of 89 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.
0.16LOEUF
pLI 1.000
Z-score 5.56
OE 0.05 (0.02–0.16)
Highly constrained

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

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.
1.12Z-score
OE missense 0.87 (0.81–0.94)
545 obs / 623.4 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.0.05 (0.02–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.81–0.94)
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.1.08
0≤1.21.6
LoF obs/exp: 2 / 39.9Missense obs/exp: 545 / 623.4Syn Z: -1.08

ClinVar Variant Classifications

89 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS55
Likely Benign11
22
Pathogenic
1
Likely Pathogenic
55
VUS
11
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
1
29
19
6
55
Likely Benign
0
3
4
4
11
Benign
0
0
0
0
0
Total132461089

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

View in ClinVar →

Protein Context — Lollipop Plot

PELP1 · 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
PELP1: Structure, biological function and clinical significance.
Sareddy GR et al.·Gene
2016Review
Overexpression of PELP1 in Lung Adenocarcinoma Promoted E(2) Induced Proliferation, Migration and Invasion of the Tumor Cells and Predicted a Worse Outcome of the Patients.
Zhang D et al.·Pathol Oncol Res
2021Cohort
Significance of PELP1 in ER-negative breast cancer metastasis.
Roy S et al.·Mol Cancer Res
2012
The Clinical Value of PELP1 for Breast Cancer: A Comparison with Multiple Cancers and Analysis in Breast Cancer Subtypes.
Wang X et al.·Cancer Res Treat
2019
Novel role of PELP1 in regulating chemotherapy response in mutant p53-expressing triple negative breast cancer cells.
Krishnan SR et al.·Breast Cancer Res Treat
2015
The prognostic significance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype.
Habashy HO et al.·Breast Cancer Res Treat
2010
The histone variant MacroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1.
Hussey KM et al.·Mol Cell Biol
2014
Cytoplasmic Localization of Proline, Glutamic Acid, Leucine-rich Protein 1 (PELP1) Induces Breast Epithelial Cell Migration through Up-regulation of Inhibitor of κB Kinase ϵ and Inflammatory Cross-talk with Macrophages.
Girard BJ et al.·J Biol Chem
2017
Clinical Evaluation of Proline, Glutamic acid, and Leucine-Rich Protein 1 Expression in Astrocytomas and Correlations with the Proliferation Marker Ki-67.
Padmavathy KP et al.·J Mol Neurosci
2021
Prognostic significance of proline, glutamic acid, leucine rich protein 1 (PELP1) in triple-negative breast cancer: a retrospective study on 129 cases.
Zhang Y et al.·BMC Cancer
2015Cohort
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