PPWD1

protein-coding

peptidylprolyl isomerase domain and WD repeat containing 1, the group of Cyclophilin peptidylprolyl isomerases|Spliceosomal C complex|Spliceosomal P complex|WD repeat domain containing

Gene summary

Enables peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nuclear body. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015342.4

Inheritance

—

ClinVar variants

U:82B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr5:65,563,236-65,587,549

External References & Databases

Ensembl (ENSG00000113593)

Transcript & Mutation Effects

hg38 • Region Span ~24.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPWD1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 79

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015342.4. 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						0
missense			78 clinvar	1 clinvar		79
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	82	1	0	83

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015342.4	RefSeq	NP_056157.1	11	MANE Select
ENST00000261308.10	Ensembl	ENSP00000261308.4	11	MANE Select
NM_001278926.2	RefSeq	NP_001265855.1	12	Standard
NM_001278927.2	RefSeq	NP_001265856.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Molecular Function

peptidyl-prolyl cis-trans isomerase activity
cyclosporin A binding

Cellular Component

nucleoplasm
nuclear body
catalytic step 2 spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261308
Coding exons: 11
Length: 24314
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	291	359	0.810	0.0000182	4311
Missense (PolyPhen)		72	117.55	0.6125		1422
Synonymous	1.23	99	116	0.855	0.00000571	1182
Loss of Function	3.09	13	31.8	0.409	0.00000207	363

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00051	0.00049	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00013	0.00013	rare
Other	0.00049	0.00049	rare

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:20676357). May be involved in pre- mRNA splicing (PubMed:11991638). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:20676357}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.832
RVIS EVS: -0.69
RVIS percentile EVS: 15.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.236

Gene Damage Prediction

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