PIN4

protein-coding

peptidylprolyl cis/trans isomerase, NIMA-interacting 4, the group of Parvulins

Gene summary

This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

MANE transcript

NM_006223.4

Inheritance

—

ClinVar variants

U:30

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:72,181,353-72,302,926

External References & Databases

Ensembl (ENSG00000102309)

Transcript & Mutation Effects

hg38 • Region Span ~121.6 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 PIN4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006223.4. 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			7 clinvar			7
missense			16 clinvar			16
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	30	0	0	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006223.4	RefSeq	NP_006214.3	4	MANE Select
ENST00000373669.8	Ensembl	ENSP00000362773.3	4	MANE Select
NM_001170747.1	RefSeq	NP_001164218.1	4	Standard
ENST00000218432.10	Ensembl	ENSP00000218432.6	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fibroblast growth factor-1

Biological Process

protein peptidyl-prolyl isomerization

Molecular Function

DNA binding
RNA binding
peptidyl-prolyl cis-trans isomerase activity
protein binding

Cellular Component

nucleus
nucleolus
mitochondrial matrix
spindle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373669
Coding exons: 4
Length: 121574
Individuals with no LoFs: 125725
Homozygous LoFs: 1
Heterozygous LoFs: 1
Defined: 125727
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.122	60	57.4	1.05	0.00000385	1027
Missense (PolyPhen)		7	14.618	0.47887		298
Synonymous	-1.31	27	19.6	1.38	0.00000137	288
Loss of Function	1.88	0	4.11	0.00	2.59e-7	84

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000012	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1 is involved as a ribosomal RNA processing factor in ribosome biogenesis. Binds to tightly bent AT-rich stretches of double-stranded DNA. {ECO:0000269|PubMed:19369196}.;

Recessive Scores

pRec: 0.221

Intolerance Scores

LoFtool: 0.102
RVIS EVS: 0.55
RVIS percentile EVS: 81.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.903

Gene Damage Prediction

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