PPIH

protein-coding

peptidylprolyl isomerase H, the group of U4/U6 small nuclear ribonucleoprotein |Cyclophilin peptidylprolyl isomerases

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 is a specific component of the complex that includes pre-mRNA processing factors PRPF3, PRPF4, and PRPF18, as well as U4/U5/U6 tri-snRNP. This protein has been shown to possess PPIase activity and may act as a protein chaperone that mediates the interactions between different proteins inside the spliceosome. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006347.4

Inheritance

—

ClinVar variants

U:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr1:42,658,335-42,676,758

External References & Databases

Ensembl (ENSG00000171960)

Transcript & Mutation Effects

hg38 • Region Span ~18.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPIH variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006347.4. 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			8 clinvar			8
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	16	0	0	16

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006347.4	RefSeq	NP_006338.1	9	MANE Select
ENST00000304979.8	Ensembl	ENSP00000306614.3	9	MANE Select
NM_001330510.2	RefSeq	NP_001317439.1	7	Standard
ENST00000372550.6	Ensembl	ENSP00000361630.2	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ppih	Danio rerio	Structure: intersegmental vessel Quality: decreased functionality abnormal

Gene / Model

Organism

Observed Phenotype

ppih

Danio rerio

Structure: intersegmental vessel

Quality: decreased functionality

abnormal

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
angiogenesis
protein folding
protein refolding

Molecular Function

peptidyl-prolyl cis-trans isomerase activity
protein binding
cyclosporin A binding
ribonucleoprotein complex binding
unfolded protein binding

Cellular Component

nucleoplasm
spliceosomal complex
cytoplasm
nuclear speck
U4/U6 x U5 tri-snRNP complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304979
Coding exons: 9
Length: 18334
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125747
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.67	55	103	0.536	0.00000498	1179
Missense (PolyPhen)		8	31.818	0.25143		417
Synonymous	0.244	35	36.9	0.949	0.00000196	327
Loss of Function	1.10	8	12.1	0.659	5.13e-7	145

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

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). Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri- snRNP complex, one of the building blocks of the spliceosome. May act as a chaperone. {ECO:0000269|PubMed:11823439, ECO:0000269|PubMed:12875835, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:9570313}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.696
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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