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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PPIL1
peptidylprolyl isomerase like 1
Chromosome 6 Β· 6p21.2
NCBI Gene: 51645Ensembl: ENSG00000137168.9HGNC: HGNC:9260UniProt: Q9Y3C6
89PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
peptidyl-prolyl cis-trans isomerase activityprotein bindingdisordered domain specific bindingmRNA splicing, via spliceosomepontocerebellar hypoplasia, type 14neurodegenerative diseasepontocerebellar hypoplasiaNon-syndromic pontocerebellar hypoplasia
✦AI Summary

PPIL1 (peptidylprolyl isomerase like 1) is a nuclear cyclophilin that functions as a critical component of the major spliceosome, playing essential roles in pre-mRNA splicing and embryonic brain development 1. As a peptidyl-prolyl isomerase, PPIL1 catalyzes the cis-trans isomerization of proline imidic peptide bonds, including prolyl peptide bond isomerization in the spliceosomal component PRP17 1. The protein forms an active isomerase-substrate interaction with PRP17, though its function in splicing appears independent of its enzymatic activity 1. PPIL1 is ubiquitously expressed with highest levels in heart tissue and localizes to the nucleus and nucleolus 2. Biallelic mutations in PPIL1 cause pontocerebellar hypoplasia type 14 (PCH14), a severe neurodegenerative disorder characterized by microcephaly, cerebellar hypoplasia, and developmental delays 13. Loss of PPIL1 function disrupts splicing integrity, particularly affecting short, GC-rich introns and genes involved in brain disorders, leading to neuron-specific apoptosis 1. Additionally, PPIL1 overexpression has been associated with colon cancer cell growth through interactions with transcriptional regulators SNW1/SKIP and stathmin 4. The protein also participates in complement-mediated tumor metastasis pathways 5.

Sources cited
1
PPIL1 is a spliceosome component essential for pre-mRNA splicing and embryonic brain development, forms isomerase-substrate interaction with PRP17, and mutations cause pontocerebellar hypoplasia with neuron-specific apoptosis
PMID: 33220177
2
PPIL1 is ubiquitously expressed with highest levels in heart tissue and encodes a cyclophilin-related protein
PMID: 8978786
3
Biallelic PPIL1 mutations cause pontocerebellar hypoplasia type 14 with severe microcephaly and developmental delays
PMID: 37159429
4
PPIL1 overexpression promotes colon cancer cell growth through interactions with SNW1/SKIP and stathmin
PMID: 16397026
5
PPIL1 participates in complement-mediated tumor metastasis pathways
PMID: 36476873
Disease Associationsβ“˜21
pontocerebellar hypoplasia, type 14Open Targets
0.77Strong
neurodegenerative diseaseOpen Targets
0.53Moderate
Non-syndromic pontocerebellar hypoplasiaOpen Targets
0.40Moderate
pontocerebellar hypoplasiaOpen Targets
0.40Moderate
dengue diseaseOpen Targets
0.37Weak
Neurodevelopmental disorderOpen Targets
0.27Weak
major depressive disorderOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
cardiac arrhythmiaOpen Targets
0.15Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
diverticular diseaseOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
familial juvenile hyperuricemic nephropathy type 1Open Targets
0.04Suggestive
polycystic kidney disease 5Open Targets
0.03Suggestive
Senior-Loken syndrome 1Open Targets
0.03Suggestive
karyomegalic interstitial nephritisOpen Targets
0.03Suggestive
systemic lupus erythematosusOpen Targets
0.03Suggestive
cancerOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.01Suggestive
Pontocerebellar hypoplasia 14UniProt
Pathogenic Variants10
NM_016059.5(PPIL1):c.41_42delinsG (p.Val14fs)Likely pathogenic
Pontocerebellar hypoplasia, type 14
β˜…β˜†β˜†β˜†2025β†’ Residue 14
NM_016059.5(PPIL1):c.280+1G>ALikely pathogenic
Pontocerebellar hypoplasia, type 14|Congenital pontocerebellar hypoplasia|not provided
β˜…β˜†β˜†β˜†2021
NM_016059.5(PPIL1):c.133C>T (p.Arg45Ter)Likely pathogenic
Neurodevelopmental disorder|Pontocerebellar hypoplasia, type 14|Congenital pontocerebellar hypoplasia
β˜…β˜†β˜†β˜†2019β†’ Residue 45
NM_016059.5(PPIL1):c.319A>G (p.Thr107Ala)Pathogenic
Congenital pontocerebellar hypoplasia|Pontocerebellar hypoplasia, type 14
β˜†β˜†β˜†β˜†2021β†’ Residue 107
NM_016059.5(PPIL1):c.295G>A (p.Ala99Thr)Pathogenic
Congenital pontocerebellar hypoplasia|Pontocerebellar hypoplasia, type 14
β˜†β˜†β˜†β˜†2021β†’ Residue 99
NM_016059.5(PPIL1):c.325G>T (p.Gly109Cys)Likely pathogenic
Congenital pontocerebellar hypoplasia
β˜†β˜†β˜†β˜†2021β†’ Residue 109
NM_016059.5(PPIL1):c.245T>C (p.Phe82Ser)Likely pathogenic
Congenital pontocerebellar hypoplasia
β˜†β˜†β˜†β˜†2021β†’ Residue 82
NM_016059.5(PPIL1):c.392G>A (p.Arg131Gln)Likely pathogenic
Congenital pontocerebellar hypoplasia
β˜†β˜†β˜†β˜†2021β†’ Residue 131
NM_016059.5(PPIL1):c.233A>G (p.Tyr78Cys)Likely pathogenic
Congenital pontocerebellar hypoplasia
β˜†β˜†β˜†β˜†2021β†’ Residue 78
NM_016059.5(PPIL1):c.301_318dup (p.Ala101_Asp106dup)Likely pathogenic
Congenital pontocerebellar hypoplasia
β˜†β˜†β˜†β˜†2021β†’ Residue 101
View on ClinVar β†—
Related Genes
XAB2Protein interaction100%RBM22Protein interaction100%SNRPA1Protein interaction100%CDC5LProtein interaction100%DHX8Protein interaction100%FRG1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
58%
Liver
37%
Bone Marrow
28%
Ovary
28%
Lung
19%
Gene Interaction Network
Click a node to explore
PPIL1XAB2RBM22SNRPA1CDC5LDHX8FRG1
PROTEIN STRUCTURE
Preparing viewer…
PDB2X7K Β· 1.15 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.07LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.69 [0.45–1.07]
RankingsWhere PPIL1 stands among ~20K protein-coding genes
  • #5,376of 20,598
    Most Researched89
  • #2,850of 5,498
    Most Pathogenic Variants10
  • #10,859of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedPPIL1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Structural and Functional Insights into Human Nuclear Cyclophilins.
PMID: 30518120
Biomolecules Β· 2018
1.00
2
Cloning, expression and chromosomal mapping of a novel cyclophilin-related gene (PPIL1) from human fetal brain.
PMID: 8978786
Cytogenet Cell Genet Β· 1996
0.90
3
Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.
PMID: 36476873
Cell Rep Β· 2022
0.80
4
Splicing Control of Pontocerebellar Development.
PMID: 33476558
Neuron Β· 2021
0.70
5
Report of new variants in PPIL1 underlying type 14 pontocerebellar hypoplasia and their associated phenotypic manifestations in two fetuses.
PMID: 37159429
Am J Med Genet A Β· 2023
0.60