BPI

protein-coding

bactericidal permeability increasing protein, the group of BPI fold containing

Gene summary

This gene encodes a lipopolysaccharide binding protein. It is associated with human neutrophil granules and has antimicrobial activity against gram-negative organisms. [provided by RefSeq, Nov 2014]

MANE transcript

NM_001725.3

Inheritance

—

ClinVar variants

U:68B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr20:38,260,141-38,337,505

External References & Databases

Ensembl (ENSG00000101425)

Transcript & Mutation Effects

hg38 • Region Span ~77.4 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 BPI variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001725.3. 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	3 clinvar	1 clinvar	5
missense			67 clinvar	6 clinvar	4 clinvar	77
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	68	9	5	82

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001725.3	RefSeq	NP_001716.3	15	MANE Select
ENST00000642449.2	Ensembl	ENSP00000494528.2	15	MANE Select
ENST00000262865.10	Ensembl	ENSP00000262865.5	13	Standard
ENST00000262865.11	Ensembl	ENSP00000262865.5	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Toll-Like Receptors Cascades
Antimicrobial peptides
Innate Immune System
Immune System

Biological Process

antimicrobial humoral response
negative regulation of interleukin-6 production
negative regulation of interleukin-8 production
negative regulation of tumor necrosis factor production
negative regulation of macrophage activation

Molecular Function

lipopolysaccharide binding

Cellular Component

extracellular region
membrane
azurophil granule lumen
specific granule lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262865
Coding exons: 15
Length: 77357
Individuals with no LoFs: 125587
Homozygous LoFs: 0
Heterozygous LoFs: 161
Defined: 125748
p: 0.000640

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.780	322	285	1.13	0.0000156	3204
Missense (PolyPhen)		79	71.037	1.1121		872
Synonymous	-0.545	128	120	1.06	0.00000800	943
Loss of Function	0.551	23	26.0	0.884	0.00000124	298

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0036	0.0036	notable
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.0023	0.0023	notable
East Asian	0.00087	0.00087	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.00065	0.00052	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa. {ECO:0000269|PubMed:1937776, ECO:0000269|PubMed:2722846}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.940
RVIS EVS: 2.6
RVIS percentile EVS: 98.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0505

Gene Damage Prediction

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