PPID

protein-coding

peptidylprolyl isomerase D, the group of Cyclophilin peptidylprolyl isomerases|Tetratricopeptide repeat domain containing

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 has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005038.3

Inheritance

ClinVar variants

U:57B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr4:158,709,127-158,723,396

External References & Databases

Ensembl (ENSG00000171497)

Transcript & Mutation Effects

hg38 • Region Span ~14.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

stutter disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000723

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPID variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005038.3. 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				1 clinvar		1
missense			55 clinvar	2 clinvar	1 clinvar	58
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	57	4	1	62

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005038.3	RefSeq	NP_005029.1	10	MANE Select
ENST00000307720.4	Ensembl	ENSP00000303754.3	10	MANE Select
ENST00000507213.1	Ensembl	ENSP00000421221.1	2	Standard
ENST00000512699.1	Ensembl	ENSP00000423207.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Necroptosis - Homo sapiens (human)
Cellular senescence - Homo sapiens (human)
NO-cGMP-PKG mediated Neuroprotection
Signal Transduction
Signaling by Nuclear Receptors

Biological Process

negative regulation of transcription by RNA polymerase II
protein peptidyl-prolyl isomerization
protein folding
apoptotic process
protein transport

Molecular Function

peptidyl-prolyl cis-trans isomerase activity
protein binding
transcription factor binding
cyclosporin A binding
estrogen receptor binding

Cellular Component

nucleus
nucleoplasm
nucleolus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307720
Coding exons: 10
Length: 14263
Individuals with no LoFs: 125251
Homozygous LoFs: 0
Heterozygous LoFs: 496
Defined: 125747
p: 0.00197

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.606	171	195	0.878	0.00000967	2431
Missense (PolyPhen)		68	73.514	0.925		951
Synonymous	-1.37	83	68.5	1.21	0.00000375	663
Loss of Function	0.973	16	20.8	0.770	0.00000101	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0015	0.0014	notable
Ashkenazi Jewish	0.0046	0.0046	notable
East Asian	0.0087	0.0087	notable
Finnish	0.0012	0.0012	notable
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0015	0.0015	notable
Other	0.0016	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:11350175, PubMed:20676357). Proposed to act as a co-chaperone in HSP90 complexes such as in unligated steroid receptors heterocomplexes. Different co- chaperones seem to compete for association with HSP90 thus establishing distinct HSP90-co-chaperone-receptor complexes with the potential to exert tissue-specific receptor activity control. May have a preference for estrogen receptor complexes and is not found in glucocorticoid receptor complexes. May be involved in cytoplasmic dynein-dependent movement of the receptor from the cytoplasm to the nucleus. May regulate MYB by inhibiting its DNA- binding activity. Involved in regulation of AHR signaling by promoting the formation of the AHR:ARNT dimer; the function is independent of HSP90 but requires the chaperone activity. Involved in regulation of UV radiation-induced apoptosis. Promotes cell viability in anaplastic lymphoma kinase-positive anaplastic large- cell lymphoma (ALK+ ALCL) cell lines. {ECO:0000269|PubMed:11350175, ECO:0000269|PubMed:18708059, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22681779, ECO:0000269|PubMed:23220213, ECO:0000269|PubMed:9659917}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.880
RVIS EVS: 0.77
RVIS percentile EVS: 87.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.471

Gene Damage Prediction

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