PPIL1

peptidylprolyl isomerase like 1, the group of Cyclophilin peptidylprolyl isomerases|Spliceosomal C complex|Spliceosomal B complex|Spliceosomal Bact complex|Spliceosomal P complex

Basic information

Region (hg38): 6:36854827-36874803

Links

ENSG00000137168 ∙ NCBI:51645 ∙ OMIM:601301 ∙ HGNC:9260 ∙ Uniprot:Q9Y3C6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia, type 14 (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia, type 14 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia, type 14 (Moderate), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPIL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPIL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			9			9
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding						0
Total	0	2	9	3	0

Variants in PPIL1

This is a list of pathogenic ClinVar variants found in the PPIL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-36855841-T-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
6-36855846-G-A			Likely benign (Nov 01, 2024)
6-36855893-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2025)
6-36855922-C-T		Congenital pontocerebellar hypoplasia	Likely pathogenic (Jan 20, 2021)
6-36855935-T-C		not specified • Pontocerebellar hypoplasia, type 14 • Congenital pontocerebellar hypoplasia	Conflicting classifications of pathogenicity (Dec 11, 2024)
6-36855939-T-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2025)
6-36855945-G-C		Inborn genetic diseases	Uncertain significance (Jan 31, 2025)
6-36855964-G-T		Pontocerebellar hypoplasia, type 14	Uncertain significance (Mar 03, 2023)
6-36855965-C-T		Pontocerebellar hypoplasia, type 14	Uncertain significance (Mar 03, 2023)
6-36855970-G-T		Pontocerebellar hypoplasia, type 14	Uncertain significance (-)
6-36855989-C-A		Congenital pontocerebellar hypoplasia	Likely pathogenic (Jan 20, 2021)
6-36855995-T-C		Congenital pontocerebellar hypoplasia • Pontocerebellar hypoplasia, type 14	Pathogenic/Likely pathogenic (Apr 29, 2021)
6-36855995-T-TATCTGGCCCCGCATTGGC		Congenital pontocerebellar hypoplasia	Likely pathogenic (Jan 20, 2021)
6-36855998-C-T		Pontocerebellar hypoplasia, type 14	Uncertain significance (Aug 20, 2021)
6-36856019-C-T		Congenital pontocerebellar hypoplasia • Pontocerebellar hypoplasia, type 14	Pathogenic/Likely pathogenic (Apr 29, 2021)
6-36856039-G-A			Benign (Mar 01, 2025)
6-36856585-C-T		Congenital pontocerebellar hypoplasia • Pontocerebellar hypoplasia, type 14	Likely pathogenic (Nov 01, 2021)
6-36856589-T-G		Pontocerebellar hypoplasia, type 14	Uncertain significance (Apr 20, 2023)
6-36856621-A-G		Congenital pontocerebellar hypoplasia	Likely pathogenic (Jan 20, 2021)
6-36856633-T-C		Congenital pontocerebellar hypoplasia	Likely pathogenic (Jan 20, 2021)
6-36871741-T-G		Pontocerebellar hypoplasia, type 14	Uncertain significance (-)
6-36871767-G-A			Likely benign (Sep 01, 2024)
6-36871796-G-A		Neurodevelopmental disorder • Pontocerebellar hypoplasia, type 14 • Congenital pontocerebellar hypoplasia	Likely pathogenic (May 02, 2019)
6-36871825-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
6-36874758-G-T			Likely benign (Jan 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPIL1	protein_coding	protein_coding	ENST00000373699	4	20198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.121	0.856	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.580	86	103	0.839	0.00000581	1091
Missense in Polyphen		24	35.271	0.68045		422
Synonymous	0.201	34	35.5	0.957	0.00000217	316
Loss of Function	1.96	3	9.55	0.314	6.25e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000417	0.000416
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346). PPIases accelerate the folding of proteins. It catalyzes the cis- trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:16595688). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:16595688, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.
• Pathway: Spliceosome - Homo sapiens (human);Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Intolerance Scores

• loftool: 0.670
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.0985
• hipred: Y
• hipred_score: 0.719
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.754

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ppil1

Gene ontology

• Biological process: mRNA splicing, via spliceosome;protein peptidyl-prolyl isomerization;protein folding
• Cellular component: nucleus;nucleoplasm;U2-type catalytic step 2 spliceosome;catalytic step 2 spliceosome
• Molecular function: peptidyl-prolyl cis-trans isomerase activity;protein binding;cyclosporin A binding;disordered domain specific binding