PPIL1

protein-coding

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

Gene summary

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]

MANE transcript

NM_016059.5

Inheritance

ClinVar variants

P:10U:27B:3

Top phenotype

pontocerebellar hypoplasia, type 14

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr6:36,854,827-36,874,803

External References & Databases

Ensembl (ENSG00000137168)

Transcript & Mutation Effects

hg38 • Region Span ~20.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pontocerebellar hypoplasia, type 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030258

Submitter: PanelApp Australia

pontocerebellar hypoplasia, type 14MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030258

Submitter: Broad Center for Mendelian Genomics

pontocerebellar hypoplasia, type 14MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030258

Submitter: Ambry Genetics

pontocerebellar hypoplasia, type 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030258

Submitter: Labcorp Genetics (formerly Invitae)

pontocerebellar hypoplasia, type 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030258

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPIL1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 17

Pontocerebellar hypoplasia, type 14Total: 12

Congenital pontocerebellar hypoplasiaTotal: 10

not providedTotal: 7

not specifiedTotal: 3

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016059.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar		3
missense		7 clinvar	27 clinvar			34
nonsense		1 clinvar				1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	0	10	27	3	0	40

Highest pathogenic variant AF is 0.000051422547

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016059.5	RefSeq	NP_057143.1	4	MANE Select
ENST00000373699.6	Ensembl	ENSP00000362803.5	4	MANE Select
ENST00000921230.1	Ensembl	ENSP00000591289.1	4	Standard
ENST00000921230.2	Ensembl	ENSP00000591289.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

mRNA splicing, via spliceosome
protein peptidyl-prolyl isomerization
protein folding

Molecular Function

peptidyl-prolyl cis-trans isomerase activity
protein binding
cyclosporin A binding
disordered domain specific binding

Cellular Component

nucleus
nucleoplasm
U2-type catalytic step 2 spliceosome
catalytic step 2 spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373699
Coding exons: 4
Length: 20198
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.580	86	103	0.839	0.00000581	1091
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool: 0.670
RVIS EVS: 0.1
RVIS percentile EVS: 61.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.754

Gene Damage Prediction

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