PELP1

Chr 17

proline, glutamate and leucine rich protein 1

Also known as: MNAR, P160

NCBI Gene: 27043 ENSG00000141456 UniProt: Q8IZL8 OMIM: 609455

This protein functions as a transcriptional coactivator for estrogen receptor-mediated gene expression and also plays a critical role in ribosome biogenesis by regulating 28S rRNA maturation and pre-60S ribosomal subunit assembly in the nucleolus. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.158). The neurodevelopmental phenotype likely reflects disruption of ribosomal function, which is essential for proper brain development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— PELP1

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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

42 VUS of 72 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.12Z-score

OE missense 0.87 (0.81–0.94)

545 obs / 623.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.16)

0≤0.351.4

Missense OE?0.87 (0.81–0.94)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 2 / 39.9Missense obs/exp: 545 / 623.4Syn Z: -1.08

This gene — mechanism propensity

0.2499th %ile

GOF

0.3293th %ile

LOF

0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

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

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign10

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	3	29	4	6	42
Likely Benign	0	6	0	4	10
Benign	0	0	0	0	0
Total	3	35	4	10	52

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap PELP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →