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PELP1

protein-coding

proline, glutamate and leucine rich protein 1, the group of Armadillo like helical domain containing|Large ribosomal subunit biogenesis complex

Gene summary

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]

MANE transcript

NM_014389.3

Inheritance

—

ClinVar variants

U:47B:7

Top phenotype

Global developmental delay

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr17:4,669,774-4,704,337

External References & Databases

Ensembl (ENSG00000141456)NCBI Gene (27043)OMIM (609455)HGNC:30134GenCCUniProt (Q8IZL8)AlphaFoldClinVar (PELP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~34.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PELP1 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 42
not providedTotal: 8
Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014389.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
4
clinvar
 12
missense
32
clinvar
3
clinvar
 35
nonsense
3
clinvar
 3
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total00477054
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_014389.3RefSeqNP_055204.417MANE Select
ENST00000572293.7EnsemblENSP00000460300.217MANE Select
NM_001278241.2RefSeqNP_001265170.115Standard
ENST00000301396.8EnsemblENSP00000301396.517Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Signaling by PTK6
  • Signal Transduction
  • pelp1 modulation of estrogen receptor activity
  • PTK6 Expression
  • AndrogenReceptor

Biological Process

  • rRNA processing
  • positive regulation of transcription by RNA polymerase II
  • cellular response to estrogen stimulus

Molecular Function

  • chromatin binding
  • RNA binding
  • protein binding
  • transcription factor binding

Cellular Component

  • nucleus
  • nucleoplasm
  • nucleolus
  • cytoplasm
  • transcriptionally active chromatin

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000574876
Coding exons
17
Length
32954
Individuals with no LoFs
124589
Homozygous LoFs
0
Heterozygous LoFs
12
Defined
124601
p
0.0000482
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.125456230.8740.00003467073
Missense (PolyPhen)135202.090.6682260
Synonymous-1.082862641.080.00001502486
Loss of Function5.56239.90.05010.00000186515

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000450.00045rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000270.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence- specific transcription factors. Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Involved in nuclear receptor signaling via its interaction with AR and NR3C1. May promote tumorigenesis via its interaction with and modulation of several oncogenes including SRC, PI3K, STAT3 and EGFR. Plays a role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes and cell migration via its interaction with SRC and PI3K. Functions as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. Regulates pre-60S association of the critical remodeling factor MDN1 (PubMed:21326211). {ECO:0000269|PubMed:11481323, ECO:0000269|PubMed:12415108, ECO:0000269|PubMed:12682072, ECO:0000269|PubMed:14963108, ECO:0000269|PubMed:15374949, ECO:0000269|PubMed:15456770, ECO:0000269|PubMed:15579769, ECO:0000269|PubMed:15994929, ECO:0000269|PubMed:16140940, ECO:0000269|PubMed:16352611, ECO:0000269|PubMed:16574651, ECO:0000269|PubMed:21326211, ECO:0000269|PubMed:22872859}.;

Recessive Scores

pRec
0.0868

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Indispensability pred.
E
Indispensability score
0.872

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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