GeneBe

PPIE

protein-coding

peptidylprolyl isomerase E, the group of Spliceosomal B complex|Spliceosomal Bact complex|Spliceosomal P complex|RNA binding motif containing|Cyclophilin peptidylprolyl isomerases|Spliceosomal C complex

Gene summary

The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein contains a highly conserved cyclophilin (CYP) domain as well as an RNA-binding domain. It was shown to possess PPIase and protein folding activities, and it also exhibits RNA-binding activity. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 1, has been identified. [provided by RefSeq, Aug 2010]

MANE transcript

NM_006112.4

Inheritance

—

ClinVar variants

U:39

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr1:39,692,182-39,763,914

External References & Databases

Ensembl (ENSG00000084072)NCBI Gene (10450)OMIM (602435)HGNC:9258GenCCUniProt (Q9UNP9)AlphaFoldClinVar (PPIE)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~71.7 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 PPIE variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 30

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006112.4. 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
2
clinvar
 2
missense
32
clinvar
 32
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00390039
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 95 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006112.4RefSeqNP_006103.110MANE Select
ENST00000324379.10EnsemblENSP00000312769.510MANE Select
NM_001195007.2RefSeqNP_001181936.110Standard
NM_001319293.2RefSeqNP_001306222.110Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Spliceosome - Homo sapiens (human)
  • DNA Repair
  • Neutrophil degranulation
  • Metabolism of RNA
  • Innate Immune System

Biological Process

  • mRNA splicing, via spliceosome
  • protein peptidyl-prolyl isomerization
  • transcription-coupled nucleotide-excision repair
  • regulation of transcription, DNA-templated
  • protein folding

Molecular Function

  • RNA binding
  • mRNA binding
  • peptidyl-prolyl cis-trans isomerase activity
  • protein binding
  • poly(A) binding

Cellular Component

  • extracellular region
  • nucleus
  • nucleoplasm
  • cytosol
  • nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000372830
Coding exons
10
Length
71733
Individuals with no LoFs
125744
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125748
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.251331800.7370.000009992088
Missense (PolyPhen)56100.340.558091155
Synonymous0.2346264.40.9630.00000360568
Loss of Function3.20317.40.1728.22e-7216

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346). Combines RNA- binding and PPIase activities (PubMed:8977107, PubMed:18258190, PubMed:20677832, PubMed:20460131). Binds mRNA and has a preference for single-stranded RNA molecules with poly-A and poly-U stretches, suggesting it binds to the poly(A)-region in the 3'-UTR of mRNA molecules (PubMed:8977107, PubMed:18258190, PubMed:20460131). Catalyzes the cis-trans isomerization of proline imidic peptide bonds in proteins (PubMed:8977107, PubMed:18258190, PubMed:20677832, PubMed:20541251). Inhibits KMT2A activity; this requires proline isomerase activity (PubMed:20677832, PubMed:20541251, PubMed:20460131). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:18258190, ECO:0000269|PubMed:20460131, ECO:0000269|PubMed:20541251, ECO:0000269|PubMed:20677832, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:8977107}.;

Recessive Scores

pRec
0.110

Intolerance Scores

LoFtool
0.284
RVIS EVS
-0.43
RVIS percentile EVS
25.15

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.981

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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