BPI

Summary

BPI (bactericidal permeability increasing protein, HGNC:1095) is a protein-coding gene on chromosome 20q11.23, encoding Bactericidal permeability-increasing protein (P17213). 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.

This gene encodes a lipopolysaccharide binding protein. It is associated with human neutrophil granules and has antimicrobial activity against gram-negative organisms.

Source: NCBI Gene 671 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 99 total
• GTEx eGene: eQTL in 37 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_001725
• Notable: 99 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1095
Approved symbol	BPI
Name	bactericidal permeability increasing protein
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	BPIFD1
Ensembl gene	ENSG00000101425
Ensembl biotype	protein_coding
OMIM	109195
Entrez	671

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000642449

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000642449, ENST00000262865, ENST00000417318, ENST00000418004, ENST00000451435, ENST00000489039, ENST00000489102, ENST00000490381, ENST00000716802, ENST00000948435, ENST00000975261, ENST00001131019

RefSeq mRNA: 1 — MANE Select: NM_001725 NM_001725

CCDS: CCDS13303

Canonical transcript exons

ENST00000642449 — 15 exons

Exon	Start	End
ENSE00000661935	38307567	38307681
ENSE00000661936	38308930	38309058
ENSE00000661937	38310491	38310652
ENSE00000661938	38311874	38311937
ENSE00000844629	38335598	38335674
ENSE00000906855	38323870	38324046
ENSE00003545079	38320183	38320274
ENSE00003566212	38318413	38318476
ENSE00003614541	38334430	38334493
ENSE00003624066	38326265	38326432
ENSE00003631358	38324774	38324833
ENSE00004030758	38331048	38331090
ENSE00004030759	38304156	38304353
ENSE00004030761	38327588	38327655
ENSE00004780876	38337146	38337505

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.5287 / max 2415.0122, expressed in 176 samples.

Highest expression (Bgee): trabecular bone tissue, bone marrow, bone marrow cell, bone element, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BPI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	1.4e-70	+0.65	20:38304149:G:C
Artery Aorta	eqtl	1.4e-65	+0.96	20:38304149:G:C
Artery Tibial	eqtl	2.7e-62	+0.71	20:38304149:G:C
Whole Blood	sqtl	1.8e-45	+1.54	20:38331034:T:G
Esophagus Gastroesophageal Junction	eqtl	3.1e-40	+0.81	20:38304149:G:C
Esophagus Muscularis	eqtl	4.0e-33	+0.62	20:38304149:G:C
Colon Sigmoid	eqtl	6.3e-33	+0.73	20:38304149:G:C
Thyroid	eqtl	2.0e-32	+0.52	20:38304274:G:C
Testis	eqtl	2.1e-30	+0.23	20:38337215:A:G
Heart Atrial Appendage	eqtl	4.7e-27	+0.58	20:38304149:G:C
Colon Transverse	eqtl	9.2e-27	+0.54	20:38304149:G:C
Artery Coronary	eqtl	7.6e-25	+0.77	20:38304149:G:C
Ovary	eqtl	8.0e-25	+0.80	20:38304149:G:C
Adipose Visceral Omentum	eqtl	5.2e-24	+0.54	20:38304149:G:C
Prostate	eqtl	7.9e-24	+0.66	20:38304149:G:C
Breast Mammary Tissue	eqtl	7.2e-19	+0.49	20:38304149:G:C
Uterus	eqtl	1.7e-16	+0.89	20:38304149:G:C
Whole Blood	eqtl	4.3e-15	-0.34	20:38313235:T:C
Adrenal Gland	eqtl	2.2e-14	+0.59	20:38304149:G:C
Stomach	eqtl	3.0e-14	+0.48	20:38304149:G:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184560	4.3336	106
184559	0.8221	115
184558	0.2944	54
184561	0.0517	4
184563	0.0167	3
184562	0.0101	3

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.17	gold quality
bone marrow	UBERON:0002371	98.76	gold quality
bone marrow cell	CL:0002092	97.79	gold quality
bone element	UBERON:0001474	96.15	gold quality
mononuclear cell	CL:0000842	88.27	gold quality
monocyte	CL:0000576	88.24	gold quality
leukocyte	CL:0000738	87.81	gold quality
left testis	UBERON:0004533	87.45	gold quality
right testis	UBERON:0004534	86.41	gold quality
sperm	CL:0000019	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.79	gold quality
granulocyte	CL:0000094	84.57	gold quality
testis	UBERON:0000473	84.08	gold quality
male germ cell	CL:0000015	83.68	silver quality
blood	UBERON:0000178	82.07	gold quality
spleen	UBERON:0002106	71.03	gold quality
adult organism	UBERON:0007023	67.41	gold quality
endocervix	UBERON:0000458	66.93	gold quality
right lung	UBERON:0002167	63.11	gold quality
descending thoracic aorta	UBERON:0002345	62.26	gold quality
adult mammalian kidney	UBERON:0000082	61.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.65	gold quality
ectocervix	UBERON:0012249	61.46	gold quality
right coronary artery	UBERON:0001625	61.11	gold quality
right ovary	UBERON:0002118	60.99	gold quality
left ovary	UBERON:0002119	59.78	gold quality
upper lobe of left lung	UBERON:0008952	57.75	gold quality
kidney epithelium	UBERON:0004819	57.60	silver quality
amniotic fluid	UBERON:0000173	57.32	silver quality
kidney	UBERON:0002113	57.10	gold quality
ovary	UBERON:0000992	56.92	gold quality
right lobe of liver	UBERON:0001114	56.84	gold quality
uterine cervix	UBERON:0000002	56.57	gold quality
frontal pole	UBERON:0002795	56.48	gold quality
metanephros	UBERON:0000081	56.40	gold quality
nasal cavity mucosa	UBERON:0001826	56.35	gold quality
upper lobe of lung	UBERON:0008948	56.25	gold quality
metanephric glomerulus	UBERON:0004736	56.01	silver quality
hindlimb stylopod muscle	UBERON:0004252	55.91	gold quality
thoracic aorta	UBERON:0001515	55.46	gold quality
ascending aorta	UBERON:0001496	55.35	gold quality
body of uterus	UBERON:0009853	55.10	gold quality
renal glomerulus	UBERON:0000074	54.97	silver quality
mammary duct	UBERON:0001765	54.96	gold quality
tibia	UBERON:0000979	54.92	silver quality
epithelium of mammary gland	UBERON:0003244	54.69	gold quality
renal medulla	UBERON:0000362	54.65	silver quality
cranial nerve II	UBERON:0000941	54.31	silver quality
left uterine tube	UBERON:0001303	54.04	gold quality
aorta	UBERON:0000947	53.55	gold quality
cortex of kidney	UBERON:0001225	53.18	gold quality
coronary artery	UBERON:0001621	52.45	gold quality
left coronary artery	UBERON:0001626	52.45	gold quality
popliteal artery	UBERON:0002250	52.26	gold quality
tibial artery	UBERON:0007610	52.23	gold quality
pancreatic ductal cell	CL:0002079	52.11	silver quality
gall bladder	UBERON:0002110	51.98	gold quality
lung	UBERON:0002048	51.63	gold quality
omental fat pad	UBERON:0010414	51.24	gold quality
peritoneum	UBERON:0002358	51.20	gold quality
liver	UBERON:0002107	51.09	gold quality
thoracic mammary gland	UBERON:0005200	50.76	gold quality
adipose tissue of abdominal region	UBERON:0007808	50.73	gold quality
metanephros cortex	UBERON:0010533	50.71	gold quality
mammary gland	UBERON:0001911	50.59	gold quality
quadriceps femoris	UBERON:0001377	50.50	gold quality
female reproductive system	UBERON:0000474	50.33	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
lower esophagus mucosa	UBERON:0035834	50.19	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
tonsil	UBERON:0002372	50.07	gold quality
vastus lateralis	UBERON:0001379	49.99	gold quality
cardiac atrium	UBERON:0002081	49.92	gold quality
right atrium auricular region	UBERON:0006631	49.91	gold quality
apex of heart	UBERON:0002098	49.90	gold quality
tibial nerve	UBERON:0001323	49.88	gold quality
epithelial cell of pancreas	CL:0000083	49.83	gold quality
lymph node	UBERON:0000029	49.78	gold quality
smooth muscle tissue	UBERON:0001135	49.44	gold quality
pigmented layer of retina	UBERON:0001782	49.40	gold quality
vagina	UBERON:0000996	49.34	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
uterus	UBERON:0000995	49.02	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
anatomical system	UBERON:0000467	48.58	gold quality
myometrium	UBERON:0001296	48.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
material anatomical entity	UBERON:0000465	48.51	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
multicellular organism	UBERON:0000468	48.49	gold quality
mucosa of transverse colon	UBERON:0004991	48.27	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	6270.80
E-ANND-3	yes	5.28

HPA expression

RNA tissue specificity: Tissue enriched

60 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	1420.3	medium
Testis	tissue	12.1	not detected
Thymus	tissue	3.5
Kidney	tissue	3.2	not detected
Spleen	tissue	1.8	low
Skin 1	tissue	1.7	not detected
Ovary	tissue	1.7	not detected
Cervix	tissue	1.6	not detected
Salivary gland	tissue	1.3	not detected
Seminal vesicle	tissue	1.1	not detected
Spinal cord	tissue	1.1
Epididymis	tissue	0.9	not detected
Vagina	tissue	0.7	not detected
Superior colliculi	tissue	0.7
Liver	tissue	0.7	not detected
Pituitary gland	tissue	0.6
Breast	tissue	0.6	not detected
Endometrium 1	tissue	0.6	not detected
Placenta	tissue	0.5	not detected
Gallbladder	tissue	0.5	not detected
Choroid plexus	tissue	0.4
Substantia nigra	tissue	0.4
Prostate	tissue	0.4	not detected
Lymph node	tissue	0.3	low
Adipose tissue	tissue	0.3	not detected
Hippocampal formation	tissue	0.3
Olfactory bulb	tissue	0.3
Fallopian tube	tissue	0.3	not detected
Heart muscle	tissue	0.2	not detected
Pons	tissue	0.2
Smooth muscle	tissue	0.2	not detected
Urinary bladder	tissue	0.2	not detected
Tongue	tissue	0.2
Amygdala	tissue	0.2
Midbrain	tissue	0.2
Medulla oblongata	tissue	0.2
Hypothalamus	tissue	0.2
Lung	tissue	0.2	not detected
Adrenal gland	tissue	0.2	not detected
Tonsil	tissue	0.2	low
Septum	tissue	0.2
Cerebral cortex	tissue	0.1	not detected
Esophagus	tissue	0.1	not detected
Motor cortex	tissue	0.1
Basal ganglia	tissue	0.1	not detected
Putamen	tissue	0.1
Nucleus accumbens	tissue	0.1
Thalamus	tissue	0.1
Cerebellum	tissue	0.1	not detected
Locus coeruleus	tissue	0.1
Corpus callosum	tissue	0.1
Entorhinal cortex	tissue	0.1
Ventral forebrain	tissue	0.1
Retrosplenial and cingulate cortex	tissue	0.1
Periaqueductal gray	tissue	0.1
Somatosensory cortex	tissue	0.1
Retrosplenial cortex	tissue	0.1
Appendix	tissue	0.1	not detected
Temporal cortex	tissue	0.1
Insular cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 137; highest nTPM — Dorsal spinal cord (1.1), Blood vessel (0.6), Area parastriata, superior (0.4), Ventral spinal cord (0.4), Median raphe nucleus (0.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPE, CEBPG, IRX1, RUNX1, SP3, SPI1

miRNA regulators (miRDB)

Targeting BPI by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-3156-5P	96.93	67.36	800
HSA-MIR-6085	96.57	64.11	621
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-6813-5P	94.68	64.20	588

Functional genomics

gnomAD constraint: pLI 1.5e-13, LOEUF 1.01, missense Z -0.171 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000642449 — one region, missense o/e 1.07.

Literature-anchored findings (GeneRIF, showing 37)

• Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epithelia (PMID:11891303)
• increased levels in fetal disease, premature rupture of membranes, and preterm labor (PMID:12710851)
• Constitutive expression of BPI, which increases upon interleukin 4 stimulation, by human dermal fibroblast was demonstrated, suggesting an important role of BPI in gram-negative bacterial clearance and a dampened response to endotoxin in the skin (PMID:12738651)
• BPI and cathepsin G are the major antigenic targets of ANCA seen in patients with systemic sclerosis (PMID:12784398)
• BPI and HNP are accumulated in the synovial cavity of patients with rheumatoid arthritis (PMID:12913926)
• In conclusion, we provide evidence for AML-1, PU.1, and Sp3 cooperatively and directly mediating BPI-expression during myeloid differentiation. (PMID:14623259)
• BPI could exist in the inner root sheath cells of human and rat hair follicles, and might play a role as a barrier against anaerobic bacteria (PMID:15009116)
• The BPI stored in human neutrophil granulocytes, is cytotoxic against Gram-negative bacteria. (PMID:15590754)
• The bactericidal/permeability increasing protein (BPI) is involved in the elimination of gram-negative bacteria. A functionally relevant single nucleotide polymorphism of the BPI gene causes an amino acid exchange (Glu216Lys). (PMID:15758620)
• Studies of BPI promoter expression in intestinal epithelial cells identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. (PMID:16282362)
• findings suggest that BPI is associated with metabolic pathways (PMID:16380496)
• BPI that is functionally active against mucoid P. aeruginosa strains is expressed in the airways of Cystic Fibrosis patients but may be hampered by autoantibodies, resulting in chronic infection. (PMID:16861658)
• The present study does not give evidence for the contribution of the BPI gene to the genetic background of chronic periodontal disease. (PMID:16893388)
• BPI has unusual dual properties of promoting retinal pericytes and retinal pigment epithelial cell growth while suppressing VEGF-induced retinal epithelial cell growth and vascular permeability (PMID:17012258)
• Reduces expression of type I inetrferon by antagonizing lipopolysaccharide-binding protein. (PMID:17239348)
• the requirement for C/EBP epsilon in mediating BPI gene expression in myeloid cells in vitro and in vivo. (PMID:17483073)
• Restriction enzyme digestion and DNA sequence analysis revealed that the sequence encoding signal peptide and bioactive N-terminal fragment of BPI had six nucleotide substitutions, compared with that of the established human BPI sequence (PMID:17488601)
• a novel role of BPI in the interaction of bacterial outer membrane vesicles with dendritic cells that may help link innate immune recognition of endotoxin to Ag delivery and presentation. (PMID:17675509)
• This review article focuses on the structural and functional properties of BPI with respect to its antimicrobial contribution to host defense during GNB infections and endotoxin-induced inflammation. (PMID:17678885)
• evaluated the role of genetic polymorphisms of the bactericidal permeability increasing protein (BPI) in pediatric patients with sepsis (PMID:17898994)
• Investigated if serum and salivary anti-BPI autoantibodies appear in the course of acute pneumonia. Presence of anti-BPI IgG on admission didn’t correlate with inflammatory markers. Salivary anti-BPI IgA didn’t appear during the course of acute pneumonia. (PMID:19702878)
• Circulating BPI could constitute a biomarker of lipid metabolism in subjects with normal glucose tolerance and could help to identify those subjects with preserved endothelial function. (PMID:20174761)
• BPI is the main target antigen for ANCA in tuberculosis and BPI-ANCA increase after treatment (PMID:20412700)
• SNP Lys216Glu is associated with Crohn’s disease and ulcerative colities (PMID:21272798)
• there is a correlation between the presence of BPI-ANCA, the properties of the colonizing bacteria and the clinical conditions of the host in cystic fibrosis (PMID:21463973)
• The bactericidal/permeability-increasing protein in the innate defence of the lower airways (PMID:21787345)
• BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD…BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers. (PMID:22409502)
• Lung function and IgA-BPI-ANCA, but not Leeds criteria, were significantly associated with adverse outcome. (PMID:23346184)
• Diminished PRRs, IFN-signature, and BPI gene expression raises the possibility that impairments in these pathways contribute to the susceptibility of LBW term infants to infection. (PMID:23626859)
• MPO and BPI in CD4(+)T-lymphocytes, and PDHA1 and MRPL42 in CD8(+) T-lymphocytes might be used as specific biomarkers of severe asthma progression. (PMID:26107902)
• Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn’s disease and ulcerative colitis. (PMID:26228368)
• BPI G645A polymorphism was associated with a decreased risk of ulcerative colitis; the BPI G645A polymorphism was not associated with the risk of crohn’s disease. (PMID:28035462)
• define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections. (PMID:30581431)
• Serum BPI protein levels are associated with inflammatory status in chronic obstructive pulmonary disease patients with pulmonary Pseudomonas aeruginosa colonization. (PMID:31106488)
• Lipopolysaccharide-Binding Protein and Bactericidal/Permeability-Increasing Protein in Lipid Metabolism and Cardiovascular Diseases. (PMID:32705592)
• BPI overexpression suppresses Treg differentiation and induces exosome-mediated inflammation in systemic lupus erythematosus. (PMID:34815797)
• Molecular Evolution of the Bactericidal/Permeability-Increasing Protein (BPIFA1) Regulating the Innate Immune Responses in Mammals. (PMID:36672756)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpi	ENSMUSG00000052922
rattus_norvegicus	Bpi	ENSRNOG00000034195
caenorhabditis_elegans		WBGENE00003812
caenorhabditis_elegans		WBGENE00008512
caenorhabditis_elegans	F10D11.6	WBGENE00008652
caenorhabditis_elegans		WBGENE00015544
caenorhabditis_elegans		WBGENE00015545
caenorhabditis_elegans		WBGENE00016951
caenorhabditis_elegans		WBGENE00018403
caenorhabditis_elegans		WBGENE00020563
caenorhabditis_elegans		WBGENE00022627

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3045315) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal immune cell physiology	1
increased T cell number	1
enlarged mesenteric lymph nodes	1
increased susceptibility to induced colitis	1
abnormal interleukin secretion	1
decreased circulating interferon-gamma level	1
abnormal circulating interleukin level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q2TBI0	75.1%	Diamond
Oryctolagus cuniculus	P17454	68.9%	Diamond
Sebastes schlegelii	A0A481NSZ4	35.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TGM2	protein-coding	7052
KIAA1755	protein-coding	85449
SNORA71B	snoRNA	26776
SNHG17	ncRNA	388796
LBP	protein-coding	3929

Protein

Protein identifiers

Bactericidal permeability-increasing protein — P17213 (reviewed: P17213)

Alternative names: CAP 57

All UniProt accessions (5): A0A0D9SFX6, A0A2R8YDF1, A0ABB0MV37, P17213, H0Y738

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Monomer. Homodimer; disulfide-linked.

Subcellular location. Secreted. Cytoplasmic granule membrane.

Tissue specificity. Restricted to cells of the myeloid series.

Domain organisation. The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested. The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues.

Similarity. Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.

RefSeq proteins (1): NP_001716* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001124	Lipid-bd_serum_glycop_C	Domain
IPR017942	Lipid-bd_serum_glycop_N	Domain
IPR017943	Bactericidal_perm-incr_a/b_dom	Homologous_superfamily
IPR017954	Lipid-bd_serum_glycop_CS	Conserved_site
IPR030675	BPI/LBP	Family
IPR032942	BPI/LBP/Plunc	Family

Pfam: PF01273, PF02886

UniProt features (79 total): strand 28, helix 18, sequence variant 11, region of interest 6, sequence conflict 6, mutagenesis site 4, turn 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
1EWF	THE 1.7 ANGSTROM CRYSTAL STRUCTURE OF BPI	X-RAY DIFFRACTION	1.7
1BP1	CRYSTAL STRUCTURE OF BPI, THE HUMAN BACTERICIDAL PERMEABILITY-INCREASING PROTEIN	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17213-F1	92.70	0.89

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted secreted proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1)

Type	Positions
Disulfide bond	166–206

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	380

Mutagenesis-validated functional residues (4)

Position	Phenotype
49	no impairment of secretion and increased propensity for dimer formation.
163	no impairment of secretion and/or biological activity. loss of dimer formation.
166	poorly secreted. loss of lps-binding and biological activity.
206	not secreted.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-6803157	Antimicrobial peptides	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-168898	Toll-like Receptor Cascades	—

MSigDB gene sets: 135 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_64, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_6_PRODUCTION, MODULE_75, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (9): lipopolysaccharide-mediated signaling pathway (GO:0031663), negative regulation of interleukin-6 production (GO:0032715), negative regulation of interleukin-8 production (GO:0032717), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of macrophage activation (GO:0043031), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), immune system process (GO:0002376), defense response to bacterium (GO:0042742)

GO Molecular Function (2): lipopolysaccharide binding (GO:0001530), lipid binding (GO:0008289)

GO Cellular Component (5): extracellular region (GO:0005576), azurophil granule lumen (GO:0035578), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Innate Immune System	3
Toll-like Receptor Cascades	1
Immune System	1

GO top-level categories

29 GO namespaces:

Category	Terms
negative regulation of cytokine production	2
cellular anatomical structure	2
secretory granule lumen	2
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
negative regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
immune response	1
defense response to symbiont	1
defense response to bacterium	1
biological_process	1
defense response	1
response to bacterium	1
lipid binding	1
carbohydrate derivative binding	1
binding	1
vacuolar lumen	1
azurophil granule	1
specific granule	1
extracellular vesicle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of interleukin-6 production	BP	direct assay
negative regulation of interleukin-8 production	BP	direct assay
negative regulation of macrophage activation	BP	direct assay
negative regulation of tumor necrosis factor production	BP	direct assay
extracellular exosome	CC	high-throughput assay
lipopolysaccharide binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 486 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPI	AMY1B	P04745	774
BPI	AMY2A	P04746	740
BPI	BPIFA1	Q9NP55	716
BPI	LTF	P02788	715
BPI	AZU1	P20160	679
BPI	CTSG	P08311	675
BPI	PRTN3	P15637	655
BPI	AMY2B	P19961	654
BPI	MPO	P05164	621
BPI	BPIFA2	Q96DR5	613
BPI	CAMP	P49913	606
BPI	ELANE	P08246	570
BPI	STATH	P02808	537
BPI	PGLYRP1	O75594	448
BPI	BPIFB1	Q8TDL5	442

IntAct

Human interaction partners of BPI in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
SLAMF9	physical association	0.400	1

BioGRID (12 interactions; top human partners by supporting records): C9orf72 (Affinity Capture-MS), CD2BP2 (Affinity Capture-MS), CIT (Affinity Capture-MS), EGFL8 (Affinity Capture-MS), GNG8 (Affinity Capture-MS), KLK10 (Affinity Capture-MS), PARK2 (Affinity Capture-MS), PARP6 (Proximity Label-MS), PARP9 (Proximity Label-MS), RHBDD1 (Affinity Capture-MS), TCEB3B (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
IRX1	“down-regulates quantity by repression”	BPI	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for BPI: 99 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

99 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	8
Benign	13

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 937):

Position(s)	Effect	Δscore	Sites
20:38304354–38304355	donor_loss	1.0000	5
20:38309038–38309039	donor_gain	1.0000	2
20:38320181–38320182	acceptor_loss	1.0000	6
20:38320275–38320276	donor_loss	1.0000	5
20:38324834–38324835	donor_loss	1.0000	2
20:38326240	acceptor_gain	1.0000
20:38326253–38326254	acceptor_gain	1.0000	2
20:38304325	donor_gain	0.9900
20:38304354	donor_loss	0.9900
20:38307565–38307566	acceptor_loss	0.9900	6

AlphaMissense

554 missense substitutions predicted likely pathogenic (of 3,200 scored), across 210 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M284	9	0.812	0.966
F387	8	0.860	0.954
F189	8	0.767	0.912
C166	7	0.864	0.917
C206	7	0.862	0.928
W122	7	0.844	0.976
F340	7	0.838	0.967
F477	7	0.816	0.956
D483	7	0.755	0.832
N449	7	0.722	0.829
G120	6	0.864	0.956
G455	6	0.845	0.950
D231	6	0.819	0.886
F427	6	0.816	0.874
F294	6	0.762	0.885
G257	5	0.938	0.977
F259	5	0.913	0.955
F135	5	0.873	0.932
F456	5	0.856	0.890
F72	5	0.839	0.895

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (TCGA)	favorable	0.000763

Disease associations

OMIM: gene MIM:109195 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST90002394_251	Monocyte percentage of white cells	7e-15
GCST90002393_277	Monocyte count	1e-10
GCST90002394_250	Monocyte percentage of white cells	1e-10
GCST90002379_61	Basophil count	2e-10
GCST90002407_513	White blood cell count	2e-9
GCST005351_9	Carboplatin disposition in epthelial ovarian cancer	9e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cadmium sulfate	increases expression	2
Arsenic Trioxide	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
aflatoxin B2	decreases methylation	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cyclophosphamide	decreases expression	1
Diazinon	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.