PPIL1

Chr 6

peptidylprolyl isomerase like 1

Also known as: CGI-124, CYPL1, PCH14, PPIase, hCyPX

NCBI Gene: 51645 ENSG00000137168 UniProt: Q9Y3C6

This peptidylprolyl isomerase functions as a component of the spliceosome in pre-mRNA splicing and catalyzes the cis-trans isomerization of proline imidic peptide bonds, playing an important role in embryonic brain development. Mutations cause pontocerebellar hypoplasia type 14, a severe early-onset neurodevelopmental disorder affecting the brainstem and cerebellum. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the cyclophilin family of peptidylprolyl isomerases (PPIases). The cyclophilins are a highly conserved, ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. Based on similarity to other PPIases, this protein could accelerate the folding of proteins and might catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.81

Clinical Summary— PPIL1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 24 VUS of 43 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.121

Z-score 1.96

OE 0.31 (0.14–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.84 (0.70–1.00)

86 obs / 102.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.14–0.81)

0≤0.351.4

Missense OE?0.84 (0.70–1.00)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 9.5Missense obs/exp: 86 / 102.5Syn Z: 0.20

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPPIL1-related neurodegenerative pontocerebellar hypoplasia with microcephalyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.77top 25%

GOF

0.6930th %ile

LOF

0.2774th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

43 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic10

VUS24

Likely Benign3

Benign1

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

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	3	7	0	0	10
VUS	0	24	0	0	24
Likely Benign	0	0	0	3	3
Benign	0	0	1	0	1
Conflicting	—				1
Total	3	31	1	3	39

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap PPIL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →