BPIFB2

Summary

BPIFB2 (BPI fold containing family B member 2, HGNC:16177) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family B member 2 (Q8N4F0).

This gene encodes a member of the lipid transfer/lipopolysaccharide binding protein (LT/LBP) gene family. It is highly expressed in hypertrophic tonsils. This gene and three other members of the LT/LBP gene family form a cluster on the long arm of chromosome 20.

Source: NCBI Gene 80341 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_025227

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16177
Approved symbol	BPIFB2
Name	BPI fold containing family B member 2
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ726C3.2, LPLUNC2
Ensembl gene	ENSG00000078898
Ensembl biotype	protein_coding
OMIM	614108
Entrez	80341

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000170150, ENST00000864169

RefSeq mRNA: 1 — MANE Select: NM_025227 NM_025227

CCDS: CCDS13210

Canonical transcript exons

ENST00000170150 — 16 exons

Exon	Start	End
ENSE00000408903	33015436	33015496
ENSE00000408907	33019580	33019750
ENSE00000661246	33008541	33008683
ENSE00000661247	33011024	33011117
ENSE00000661248	33012803	33012907
ENSE00000661249	33013810	33013956
ENSE00000661250	33017042	33017102
ENSE00000661251	33018259	33018350
ENSE00000661252	33018637	33018822
ENSE00000661253	33019062	33019115
ENSE00000661254	33020328	33020395
ENSE00000661255	33020542	33020587
ENSE00000661257	33021281	33021344
ENSE00000661258	33021723	33021799
ENSE00001048840	33007704	33007760
ENSE00001852366	33023342	33023703

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 98.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.4013 / max 1613.1277, expressed in 36 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184074	3.3350	35
184073	0.0663	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	98.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.75	gold quality
minor salivary gland	UBERON:0001830	93.30	gold quality
saliva-secreting gland	UBERON:0001044	91.57	gold quality
mouth mucosa	UBERON:0003729	88.11	gold quality
nasal cavity mucosa	UBERON:0001826	80.56	gold quality
pharyngeal mucosa	UBERON:0000355	78.73	gold quality
urethra	UBERON:0000057	74.95	gold quality
oral cavity	UBERON:0000167	74.16	gold quality
tongue	UBERON:0001723	72.80	gold quality
parotid gland	UBERON:0001831	72.02	silver quality
superior surface of tongue	UBERON:0007371	69.51	gold quality
myocardium	UBERON:0002349	66.40	gold quality
sperm	CL:0000019	65.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	64.52	gold quality
body of tongue	UBERON:0011876	63.39	gold quality
nasal cavity epithelium	UBERON:0005384	63.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.16	gold quality
tonsil	UBERON:0002372	62.80	gold quality
biceps brachii	UBERON:0001507	61.68	gold quality
Brodmann (1909) area 46	UBERON:0006483	59.81	gold quality
vastus lateralis	UBERON:0001379	59.28	gold quality
quadriceps femoris	UBERON:0001377	58.86	gold quality
gingiva	UBERON:0001828	57.98	silver quality
esophagus squamous epithelium	UBERON:0006920	56.25	gold quality
deltoid	UBERON:0001476	56.15	gold quality
trabecular bone tissue	UBERON:0002483	55.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	55.21	gold quality
tendon of biceps brachii	UBERON:0008188	54.28	gold quality
cartilage tissue	UBERON:0002418	54.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	10.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting BPIFB2, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470

Literature-anchored findings (GeneRIF, showing 2)

• BPIL1 maps to Chromosome 20q11; thus, these novel genes form a cluster with BPI and two other members of the LT/LBP gene family on the long arm of human Chr 20. AA sequence is reported. (PMID:12185532)
• BPIFB2 is highly expressed in ““cold”” lung adenocarcinoma and decreases T cell chemotaxis via activation of the STAT3 pathway. (PMID:35240266)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifb2	ENSMUSG00000027481
rattus_norvegicus	Bpifb2	ENSRNOG00000012197
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), 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 2 — Q8N4F0 (reviewed: Q8N4F0)

Alternative names: Bactericidal/permeability-increasing protein-like 1, Long palate, lung and nasal epithelium carcinoma-associated protein 2, RYSR

All UniProt accessions (1): Q8N4F0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Highly expressed in tonsils, especially in hypertrophic tonsils. Detected at very low levels in fetal liver.

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

RefSeq proteins (1): NP_079503* (*=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
IPR030675	BPI/LBP	Family
IPR051660	BPI_fold-BPI/LBP	Family

Pfam: PF01273, PF02886

UniProt features (14 total): glycosylation site 4, sequence variant 3, sequence conflict 2, modified residue 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4F0-F1	89.04	0.71

Functional residue map

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

Post-translational modifications (2): 52, 60

Disulfide bonds (1): 137–174

Glycosylation sites (4): 96, 151, 293, 332

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6803157	Antimicrobial peptides
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 39 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, STONER_ESOPHAGEAL_CARCINOGENESIS_UP, DBP_Q6, chr20q11, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, MODULE_69, CCAWNWWNNNGGC_UNKNOWN, GOMF_LIPID_BINDING, RICKMAN_HEAD_AND_NECK_CANCER_D, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_REGULATION_OF_INSULIN_LIKE_GROWTH_FACTOR_IGF_TRANSPORT_AND_UPTAKE_BY_INSULIN_LIKE_GROWTH_FACTOR_BINDING_PROTEINS_IGFBPS, REACTOME_ANTIMICROBIAL_PEPTIDES, HHEX_TARGET_GENES, PAX3_TARGET_GENES, MIR6127

GO Biological Process (0):

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

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), extracellular exosome (GO:0070062), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of proteins	2
Innate Immune System	1
Post-translational protein modification	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFB2	BPIFB1	Q8TDL5	801
BPIFB2	BPIFA1	Q9NP55	663
BPIFB2	LYG2	Q86SG7	660
BPIFB2	BPIFA3	Q9BQP9	628
BPIFB2	BPIFA2	Q96DR5	582
BPIFB2	YLPM1	P49750	486
BPIFB2	EFCAB8	A8MWE9	473
BPIFB2	A0A2R8Y455	A0A2R8Y455	454
BPIFB2	FREM1	Q5H8C1	453
BPIFB2	COMMD7	Q86VX2	437
BPIFB2	SUN5	Q8TC36	436
BPIFB2	SCARA3	Q6AZY7	429
BPIFB2	PIMREG	Q9BSJ6	428
BPIFB2	ZG16B	Q96DA0	415
BPIFB2	PTGR1	Q14914	414

IntAct

13 interactions, top by confidence:

A	B	Type	Score
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
BPIFB2	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
	AP3B1	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
EBF2	LILRA5	psi-mi:“MI:0914”(association)	0.350
ITLN2	IGLC7	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Proximity Label-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (Affinity Capture-MS), BPIFB2 (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: Q8C1E1, Q8N4F0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2475 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33013952:AACAG:A	donor_loss	1.0000
20:33013954:CAGG:C	donor_loss	1.0000
20:33013956:GGT:G	donor_loss	1.0000
20:33013958:T:G	donor_loss	1.0000
20:33017029:T:TA	acceptor_gain	1.0000
20:33017040:A:AG	acceptor_gain	1.0000
20:33017041:G:GC	acceptor_gain	1.0000
20:33017041:GCT:G	acceptor_gain	1.0000
20:33017041:GCTGT:G	acceptor_gain	1.0000
20:33017100:TTGGT:T	donor_loss	1.0000
20:33017101:TGG:T	donor_loss	1.0000
20:33017103:G:GG	donor_gain	1.0000
20:33017103:GTAA:G	donor_loss	1.0000
20:33017104:T:A	donor_loss	1.0000
20:33018242:A:AG	acceptor_gain	1.0000
20:33018242:ACCCT:A	acceptor_gain	1.0000
20:33018243:C:G	acceptor_gain	1.0000
20:33018246:T:A	acceptor_gain	1.0000
20:33018247:G:A	acceptor_gain	1.0000
20:33018253:A:AG	acceptor_gain	1.0000
20:33018253:AT:A	acceptor_gain	1.0000
20:33018254:T:G	acceptor_gain	1.0000
20:33018254:T:TA	acceptor_gain	1.0000
20:33018254:TGAA:T	acceptor_loss	1.0000
20:33018257:A:AC	acceptor_loss	1.0000
20:33018257:A:AG	acceptor_gain	1.0000
20:33018258:G:GG	acceptor_gain	1.0000
20:33018351:G:GG	donor_gain	1.0000
20:33018632:TACA:T	acceptor_loss	1.0000
20:33018634:CAGGC:C	acceptor_loss	1.0000

AlphaMissense

2926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33008657:G:C	R28P	0.966
20:33018282:T:C	S201P	0.963
20:33023360:A:C	S452R	0.950
20:33023362:T:A	S452R	0.950
20:33023362:T:G	S452R	0.950
20:33018294:T:G	Y205D	0.945
20:33023355:T:A	I450K	0.941
20:33017080:T:A	N185K	0.938
20:33017080:T:G	N185K	0.938
20:33018743:T:C	L259P	0.934
20:33019617:T:C	L316P	0.933
20:33021339:T:C	L418P	0.933
20:33020371:T:A	L375H	0.928
20:33008654:T:A	V27D	0.924
20:33020376:G:A	G377R	0.922
20:33020376:G:C	G377R	0.922
20:33020371:T:C	L375P	0.920
20:33018691:T:C	F242L	0.917
20:33018693:T:A	F242L	0.917
20:33018693:T:G	F242L	0.917
20:33018313:C:A	P211H	0.912
20:33013896:T:A	V132D	0.909
20:33017045:T:A	C174S	0.909
20:33017046:G:C	C174S	0.909
20:33021747:T:A	L428H	0.909
20:33013910:T:C	C137R	0.901
20:33019674:T:C	L335P	0.899
20:33018787:G:C	A274P	0.896
20:33023355:T:G	I450R	0.896
20:33013854:C:A	A118D	0.895

dbSNP variants (sampled 300 via entrez): RS1000318524 (20:33013012 C>T), RS1000445001 (20:33007662 C>T), RS1000540211 (20:33011985 A>C), RS1000640810 (20:33006382 A>T), RS1000996413 (20:33017494 A>G), RS1000996647 (20:33014674 G>A), RS1001057740 (20:33011778 A>G), RS1001116607 (20:33023228 C>A,T), RS1001227878 (20:33014595 G>A,T), RS1001297426 (20:33023005 G>C), RS1001333694 (20:33009136 G>A), RS1001459357 (20:33011527 C>T), RS1001593656 (20:33011203 GC>G), RS1001664858 (20:33020160 C>T), RS1001724720 (20:33014373 G>A)

Disease associations

OMIM: gene MIM:614108 | 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
GCST008811_36	Alcohol consumption (drinks per week)	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
dicrotophos	increases expression	1
bisphenol A	affects expression	1
CGP 52608	affects binding, increases reaction	1
Ampicillin	increases expression	1
Diazinon	increases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Quercetin	affects expression	1
Valproic Acid	affects cotreatment, increases expression	1
Oxyquinoline	increases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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