BPIFB1

Summary

BPIFB1 (BPI fold containing family B member 1, HGNC:16108) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family B member 1 (Q8TDL5). May play a role in innate immunity in mouth, nose and lungs.

The protein encoded by this gene may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. The encoded protein is secreted and is a member of the BPI/LBP/PLUNC protein superfamily. This gene is found with other members of the superfamily in a cluster on chromosome 20.

Source: NCBI Gene 92747 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_033197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16108
Approved symbol	BPIFB1
Name	BPI fold containing family B member 1
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ1187J4.1, MGC14597, bA49G10.6, LPLUNC1, VEMSGP
Ensembl gene	ENSG00000125999
Ensembl biotype	protein_coding
OMIM	621168
Entrez	92747

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000253354, ENST00000423645, ENST00000464032, ENST00000865831, ENST00000865832, ENST00000865833, ENST00000865834, ENST00000865835, ENST00000865836, ENST00000865837, ENST00000865838, ENST00000865839, ENST00000865840, ENST00000865841, ENST00000865842, ENST00000865843, ENST00000865844, ENST00000960538, ENST00000960539, ENST00000960540, ENST00000960541, ENST00000960542, ENST00000960543, ENST00000960544

RefSeq mRNA: 1 — MANE Select: NM_033197 NM_033197

CCDS: CCDS13218

Canonical transcript exons

ENST00000253354 — 16 exons

Exon	Start	End
ENSE00000898460	33288741	33288882
ENSE00000898461	33289885	33289992
ENSE00000898462	33290957	33291106
ENSE00000898463	33291907	33291988
ENSE00000991596	33297525	33297588
ENSE00001153506	33286033	33286188
ENSE00001179682	33283214	33283254
ENSE00001630113	33309708	33309871
ENSE00003460658	33303958	33304025
ENSE00003483223	33302916	33303074
ENSE00003487125	33301233	33301412
ENSE00003548442	33299899	33299984
ENSE00003620603	33306911	33306987
ENSE00003645723	33304846	33304891
ENSE00003685377	33306002	33306065
ENSE00003692567	33302359	33302412

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 9.4757 / max 9987.1935, expressed in 74 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184137	5.7253	37
184136	2.2728	45
184135	1.4666	48
184134	0.0110	6

Top tissues by expression

229 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.98	gold quality
bronchus	UBERON:0002185	99.98	gold quality
trachea	UBERON:0003126	99.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.93	gold quality
nasal cavity epithelium	UBERON:0005384	99.90	gold quality
nasal cavity mucosa	UBERON:0001826	99.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.89	gold quality
adult organism	UBERON:0007023	95.91	gold quality
parotid gland	UBERON:0001831	92.86	gold quality
epithelium of nasopharynx	UBERON:0001951	91.60	gold quality
minor salivary gland	UBERON:0001830	85.98	gold quality
saliva-secreting gland	UBERON:0001044	85.52	gold quality
pharyngeal mucosa	UBERON:0000355	83.60	gold quality
mouth mucosa	UBERON:0003729	80.70	gold quality
urethra	UBERON:0000057	78.23	gold quality
pylorus	UBERON:0001166	77.27	gold quality
oral cavity	UBERON:0000167	77.22	gold quality
tongue	UBERON:0001723	75.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.97	gold quality
epithelial cell of pancreas	CL:0000083	72.26	gold quality
gall bladder	UBERON:0002110	71.00	gold quality
body of stomach	UBERON:0001161	70.93	gold quality
stomach	UBERON:0000945	70.09	gold quality
right lung	UBERON:0002167	69.99	gold quality
body of tongue	UBERON:0011876	69.89	gold quality
superior surface of tongue	UBERON:0007371	69.70	gold quality
left testis	UBERON:0004533	68.95	gold quality
endocervix	UBERON:0000458	68.63	gold quality
right testis	UBERON:0004534	68.45	gold quality
testis	UBERON:0000473	66.86	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	20106.99
E-CURD-114	yes	16301.67
E-GEOD-86618	yes	14101.53
E-GEOD-130148	yes	11221.30
E-HCAD-1	yes	8764.00
E-MTAB-7303	no	9.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

3 targeting BPIFB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4742-5P	98.89	68.41	1542

Literature-anchored findings (GeneRIF, showing 15)

• LPLUNC1 is found to be down-expressed in 33 of 48 nasopharyngeal carcinoma biopsies. (PMID:12874788)
• We found a significant association of cholera with a marker in the promoter region of LPLUNC1 (rs11906665), a member of a family of evolutionarily conserved innate immunity proteins (PMID:19212328)
• LPLUNC1 is an abundant, secreted product of goblet cells and minor mucosal glands of the respiratory tract and oral cavity and suggest that the protein functions in the complex milieu that protects the mucosal surfaces in these locations. (PMID:20237794)
• These results demonstrate that LPLUNC1 is expressed in Paneth cells and likely plays a role in modulating host inflammatory responses to Vibrio cholerae infection. (PMID:21900486)
• It was shown that there was a significant increase in LPLUNC1 in the airways of patients with cystic fibrosis, but it is unclear if this increase influences the development of lung disease. (PMID:22767025)
• LPLUNC1 delays nasopharyngeal carcinoma cell growth by inhibiting the MAP Kinase and cyclin D1/E2F pathways. (PMID:23650533)
• Results suggest that LPLUNC1 can inhibit inflammation and nasopharyngeal carcinoma (NPC) growth by downregulating the Stat3 pathway. (PMID:23708661)
• Autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of interstitial lung disease. (PMID:24107778)
• The G allele of rs1078761 may be detrimental to lung function in cystic fibrosis owing to decreased levels of BPIFA1 and BPIFB1. (PMID:25574903)
• higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with chronic obstructive pulmonary disease. BPIFB1 may be involved in the pathogenesis of smoking-related lung diseases. (PMID:25979078)
• Results showed that BPIFB1 expression markedly inhibited NPC cell migration, invasion, and lung-metastatic abilities. Additionally, identification of two BPIFB1-interacting proteins, VTN and VIM, showed that BPIFB1 reduced VTN expression and the formation of a VTN-integrin alphaV complex in NPC cells, leading to inhibition of the FAK/Src/ERK signalling pathway. (PMID:29123267)
• BPIFA1 and BPIFB1 expressions are correlated with goblet cell metaplasia and inversely correlated with lung function parameters of airway obstruction (FEV1 and FEV1/FVC) in COPD patients. (PMID:29296079)
• BPIFB1 negatively regulates its interactor VTN, thereby inhibiting VTN-induced proliferation, antiapoptotic effects, G2/M phase arrest, DSB repair, and the activation of the ATM-Chk2 and ATR-Chk1 pathways after irradiation. (PMID:29568064)
• A novel mechanism underlying the anticancer effect of LPLUNC1 and clarifying that PHB1 may represent a novel, promising candidate tumour suppressor gene in Nasopharyngeal carcinoma, with potential therapeutic target value. (PMID:30886235)
• BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance. (PMID:37847709)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifb1	ENSMUSG00000027485
rattus_norvegicus	Bpifb1	ENSRNOG00000015468
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

BPI fold-containing family B member 1 — Q8TDL5 (reviewed: Q8TDL5)

Alternative names: Long palate, lung and nasal epithelium carcinoma-associated protein 1, von Ebner minor salivary gland protein

All UniProt accessions (2): Q8TDL5, A2A2R0

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in innate immunity in mouth, nose and lungs. Binds bacterial lipopolysaccharide (LPS) and modulates the cellular responses to LPS.

Subcellular location. Secreted.

Tissue specificity. Detected in duodenum mucosal crypts of cholera patients, near Paneth cells (at protein level). Detected in trachea, nasal septal epithelium and lung.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDL5-1	1	yes
Q8TDL5-2	2

RefSeq proteins (1): NP_149974* (*=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
IPR021193	Bpifb1	Family

Pfam: PF01273, PF02886

UniProt features (19 total): sequence variant 8, splice variant 4, glycosylation site 3, signal peptide 1, chain 1, sequence conflict 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDL5-F1	88.26	0.73

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): 158–201

Glycosylation sites (3): 48, 264, 401

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 92 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_4_SIGNALING_PATHWAY, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_INNATE_IMMUNE_RESPONSE_IN_MUCOSA, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, RYTTCCTG_ETS2_B, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, TURASHVILI_BREAST_CARCINOMA_DUCTAL_VS_LOBULAR_UP

GO Biological Process (4): innate immune response in mucosa (GO:0002227), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (1): lipid binding (GO:0008289)

GO Cellular Component (3): extracellular region (GO:0005576), extracellular exosome (GO:0070062), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mucosal immune response	1
innate immune response	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
biological_process	1
immune response	1
defense response to symbiont	1
binding	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFB1	BPIFB2	Q8N4F0	801
BPIFB1	BPIFA2	Q96DR5	697
BPIFB1	KCNRG	Q8N5I3	670
BPIFB1	C6orf58	Q6P5S2	641
BPIFB1	BPIFB6	Q8NFQ5	601
BPIFB1	BPIFA3	Q9BQP9	600
BPIFB1	BPIFB3	P59826	592
BPIFB1	MUC5B	Q9HC84	582
BPIFB1	MUC5AC	P98088	577
BPIFB1	SERPINB3	P29508	556
BPIFB1	SCGB3A1	Q96QR1	539
BPIFB1	BPIFB4	P59827	503
BPIFB1	BPI	P17213	479
BPIFB1	SERPINB13	Q9UIV8	478
BPIFB1	SERPINB10	P48595	472

IntAct

62 interactions, top by confidence:

A	B	Type	Score
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
BPIFB1	MLLT3	psi-mi:“MI:0914”(association)	0.530
TMEM237	CLGN	psi-mi:“MI:0914”(association)	0.530
PCK2	IGHA1	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
Ikbip	LTF	psi-mi:“MI:0915”(physical association)	0.400
PB2	BPIFB1	psi-mi:“MI:0915”(physical association)	0.370
ZCCHC17	SHTN1	psi-mi:“MI:0914”(association)	0.350
SNX27	IGLL5	psi-mi:“MI:0914”(association)	0.350
CDKAL1	CIAO1	psi-mi:“MI:0914”(association)	0.350
TMEM237	JCHAIN	psi-mi:“MI:0914”(association)	0.350
PCK2	PIGR	psi-mi:“MI:0914”(association)	0.350
ARHGAP12	IGHA1	psi-mi:“MI:0914”(association)	0.350
GSK3B	PRSS37	psi-mi:“MI:0914”(association)	0.350
CLK1	PIGR	psi-mi:“MI:0914”(association)	0.350
PIK3CA	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
CXorf1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
GJB5	IGLL5	psi-mi:“MI:0914”(association)	0.350
TMEM176B	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), MLLT1 (Affinity Capture-MS), MLLT3 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), TIMM50 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A481NSZ4, A0JPN3, A2BGH0, A6QP57, D4A5U3, G3HIK4, O02668, O76879, P11597, P17213, P17453, P17454, P18428, P19823, P19827, P22687, P47896, P55058, P55065, P59826, P59827, P97278, Q05701, Q05704, Q08188, Q08189, Q0VCM5, Q10011, Q24764, Q28739, Q29052, Q2TBI0, Q61114, Q61702, Q61703, Q61805, Q63313, Q67E05, Q6AXU0, Q80ZU7

Diamond homologs: A0JPN3, Q61114, Q8SPF8, Q8TDL5, P97361, Q5XW65, Q8K4I4, Q8SPU5, Q9CQX3, Q9NP55

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2644 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33288739:A:AG	acceptor_gain	1.0000
20:33288740:G:GG	acceptor_gain	1.0000
20:33288740:GA:G	acceptor_gain	1.0000
20:33288740:GAGCT:G	acceptor_gain	1.0000
20:33288880:CTGG:C	donor_loss	1.0000
20:33288881:TGGT:T	donor_loss	1.0000
20:33288883:G:GA	donor_loss	1.0000
20:33288884:T:A	donor_loss	1.0000
20:33289880:TCCA:T	acceptor_loss	1.0000
20:33289881:CCAG:C	acceptor_loss	1.0000
20:33289883:A:AG	acceptor_gain	1.0000
20:33289883:A:C	acceptor_loss	1.0000
20:33289884:G:A	acceptor_loss	1.0000
20:33289884:G:GG	acceptor_gain	1.0000
20:33289884:GGCT:G	acceptor_gain	1.0000
20:33289989:ACAC:A	donor_gain	1.0000
20:33289990:CAC:C	donor_gain	1.0000
20:33289991:AC:A	donor_gain	1.0000
20:33289993:G:GG	donor_gain	1.0000
20:33289994:TGA:T	donor_loss	1.0000
20:33291107:G:GG	donor_gain	1.0000
20:33291901:T:TA	acceptor_gain	1.0000
20:33291905:A:G	acceptor_gain	1.0000
20:33291986:CAGGT:C	donor_loss	1.0000
20:33291987:AGGT:A	donor_loss	1.0000
20:33291989:G:GC	donor_loss	1.0000
20:33291990:T:G	donor_loss	1.0000
20:33297587:GG:G	donor_gain	1.0000
20:33297588:GG:G	donor_gain	1.0000
20:33299897:A:AG	acceptor_gain	1.0000

AlphaMissense

3146 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33303061:T:C	F376S	0.977
20:33297528:T:A	C201S	0.971
20:33297529:G:C	C201S	0.971
20:33297528:T:C	C201R	0.966
20:33303961:G:C	A382P	0.965
20:33304886:T:C	F417L	0.965
20:33304888:C:A	F417L	0.965
20:33304888:C:G	F417L	0.965
20:33303060:T:C	F376L	0.963
20:33303062:C:A	F376L	0.963
20:33303062:C:G	F376L	0.963
20:33289979:G:C	A118P	0.960
20:33288756:T:C	L44P	0.956
20:33291006:G:C	A139P	0.953
20:33303030:T:C	F366L	0.948
20:33303032:T:A	F366L	0.948
20:33303032:T:G	F366L	0.948
20:33288744:T:C	L40P	0.946
20:33291063:T:C	C158R	0.945
20:33291065:T:G	C158W	0.944
20:33289980:C:A	A118D	0.941
20:33297529:G:A	C201Y	0.941
20:33291063:T:A	C158S	0.940
20:33291064:G:C	C158S	0.940
20:33289968:T:C	L114P	0.938
20:33303967:T:C	S384P	0.934
20:33291064:G:A	C158Y	0.933
20:33303022:T:C	L363P	0.933
20:33286159:T:C	L29P	0.931
20:33304887:T:G	F417C	0.931

dbSNP variants (sampled 300 via entrez): RS1000062882 (20:33308227 C>T), RS1000207093 (20:33286547 G>T), RS1000252385 (20:33310077 T>C), RS1000391364 (20:33281621 G>A), RS1000532540 (20:33308802 C>A,G,T), RS1000547284 (20:33285537 C>A,G), RS1000593580 (20:33288325 G>A,C), RS1000663855 (20:33286835 C>A,T), RS1000948233 (20:33285439 C>A,T), RS1000998276 (20:33296820 C>T), RS1001006477 (20:33302881 T>TTGGGAGGCCACA), RS1001150533 (20:33293561 G>A), RS1001265453 (20:33288054 C>T), RS1001612154 (20:33287829 T>C,G), RS1001628986 (20:33283130 G>A)

Disease associations

OMIM: gene MIM:621168 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_253	Blood protein levels	8.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
hempseed oil	affects cotreatment, decreases secretion	1
bisphenol A	decreases methylation	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	decreases expression	1
Estradiol	affects binding, increases expression	1
Glycerol	affects cotreatment, decreases secretion	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Propylene Glycol	decreases secretion, affects cotreatment	1
alpha-Tocopherol	affects cotreatment, decreases secretion	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.