PI15

protein-coding

peptidase inhibitor 15, the group of CAP superfamily

Gene summary

This gene encodes a trypsin inhibitor. The protein shares similarity to insect venom allergens, mammalian testis-specific proteins and plant pathogenesis-related proteins. It is frequently expressed in human neuroblastoma and glioblastoma cell lines, and thus may play a role in the central nervous system. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015886.5

Inheritance

—

ClinVar variants

U:30B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr8:74,824,534-74,855,029

External References & Databases

Ensembl (ENSG00000137558)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 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 PI15 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015886.5. 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			1 clinvar	1 clinvar	2 clinvar	4
missense			29 clinvar	1 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	30	2	2	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015886.5	RefSeq	NP_056970.1	5	MANE Select
ENST00000260113.7	Ensembl	ENSP00000260113.2	5	MANE Select
NM_001324403.2	RefSeq	NP_001311332.1	5	Standard
ENST00000523773.1	Ensembl	ENSP00000428567.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

multicellular organism development
biological_process
negative regulation of peptidase activity

Molecular Function

peptidase inhibitor activity

Cellular Component

extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260113
Coding exons: 5
Length: 30493
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	121	156	0.775	0.00000908	1674
Missense (PolyPhen)		52	70.852	0.73393		737
Synonymous	-0.160	60	58.4	1.03	0.00000363	499
Loss of Function	2.11	5	13.3	0.376	6.48e-7	152

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine protease inhibitor which displays weak inhibitory activity against trypsin (PubMed:8882727). May play a role in facial patterning during embryonic development (By similarity). {ECO:0000250|UniProtKB:Q98ST6, ECO:0000269|PubMed:8882727}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.801
RVIS EVS: 0.24
RVIS percentile EVS: 69.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.173

Gene Damage Prediction

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