BPIFB4

Summary

BPIFB4 (BPI fold containing family B member 4, HGNC:16179) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family B member 4 (P59827). May have the capacity to recognize and bind specific classes of odorants.

Predicted to enable lipid binding activity. Located in actin cytoskeleton and cytosol.

Source: NCBI Gene 149954 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 113 total
• MANE Select transcript: NM_182519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16179
Approved symbol	BPIFB4
Name	BPI fold containing family B member 4
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ726C3.5, LPLUNC4
Ensembl gene	ENSG00000186191
Ensembl biotype	protein_coding
OMIM	615718
Entrez	149954

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000375483, ENST00000445356, ENST00000494121, ENST00000674031

RefSeq mRNA: 1 — MANE Select: NM_182519 NM_182519

CCDS: CCDS13213

Canonical transcript exons

ENST00000375483 — 18 exons

Exon	Start	End
ENSE00001331679	33104810	33104873
ENSE00001331681	33102972	33103014
ENSE00001331683	33100426	33100493
ENSE00001331684	33097617	33097787
ENSE00001331689	33095100	33095153
ENSE00001331693	33092458	33092658
ENSE00001331708	33086021	33086164
ENSE00001331712	33084892	33084996
ENSE00001331716	33083367	33083874
ENSE00001633209	33080469	33080576
ENSE00001660166	33082938	33083000
ENSE00002285700	33081512	33081632
ENSE00003494346	33088966	33089029
ENSE00003584988	33107744	33107820
ENSE00003626367	33090708	33090799
ENSE00003647719	33089498	33089558
ENSE00003691549	33111414	33111751
ENSE00003916305	33079643	33079703

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 86.21.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0250 / max 19.2836, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184092	0.0250	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.71	gold quality
adenohypophysis	UBERON:0002196	78.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.50	gold quality
pituitary gland	UBERON:0000007	73.78	gold quality
cerebellar vermis	UBERON:0004720	61.55	gold quality
nasal cavity mucosa	UBERON:0001826	59.34	gold quality
buccal mucosa cell	CL:0002336	50.52	silver quality
left testis	UBERON:0004533	48.38	gold quality
testis	UBERON:0000473	47.32	gold quality
right testis	UBERON:0004534	46.08	gold quality
tonsil	UBERON:0002372	46.00	silver quality
thymus	UBERON:0002370	45.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	45.33	gold quality
right atrium auricular region	UBERON:0006631	44.74	gold quality
cardiac atrium	UBERON:0002081	44.61	gold quality
quadriceps femoris	UBERON:0001377	44.07	gold quality
upper leg skin	UBERON:0004262	43.41	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
sural nerve	UBERON:0015488	43.24	gold quality
epithelium of nasopharynx	UBERON:0001951	42.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	42.59	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
subthalamic nucleus	UBERON:0001906	42.30	gold quality
nasal cavity epithelium	UBERON:0005384	41.82	gold quality
vastus lateralis	UBERON:0001379	41.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.57	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	41.32	gold quality
colonic epithelium	UBERON:0000397	41.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting BPIFB4, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-924	97.78	66.21	681
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-591	96.29	68.16	611

Literature-anchored findings (GeneRIF, showing 12)

• Longevity-associated variant-BPIFB4 may represent a novel therapeutic tool to fight endothelial dysfunction and promote vascular reparative processes. (PMID:26034043)
• In conclusion, BPIFB4 and CXCR4 expression classify long-lived individuals health status that correlates with maintained mononuclear cell migration. (PMID:28121621)
• LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent mechanism. (PMID:28419216)
• RV-BPIFB4 acts directly on blood pressure homeostasis and may represent a novel biomarker of vascular dysfunction and hypertension. (PMID:28852218)
• The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury. (PMID:30377885)
• Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. (PMID:31289820)
• LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. (PMID:31461407)
• Circulating BPIFB4 Levels Associate With and Influence the Abundance of Reparative Monocytes and Macrophages in Long Living Individuals. (PMID:32547549)
• New Insights for BPIFB4 in Cardiovascular Therapy. (PMID:32998388)
• The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. (PMID:35053408)
• BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice. (PMID:37582912)
• The longevity-associated BPIFB4 gene guarantees vascular homeostasis and immune protection through platelets. (PMID:38884925)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifb4	ENSMUSG00000074665
rattus_norvegicus	Bpifb4	ENSRNOG00000034174
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

BPI fold-containing family B member 4 — P59827 (reviewed: P59827)

Alternative names: Ligand-binding protein RY2G5, Long palate, lung and nasal epithelium carcinoma-associated protein 4

All UniProt accessions (3): A0A669KBJ0, P59827, F8WEG9

UniProt curated annotations — full annotation on UniProt →

Function. May have the capacity to recognize and bind specific classes of odorants. May act as a carrier molecule, transporting odorants across the mucus layer to access receptor sites. May serve as a primary defense mechanism by recognizing and removing potentially harmful odorants or pathogenic microorganisms from the mucosa or clearing excess odorant from mucus to enable new odorant stimuli to be received.

Subcellular location. Secreted. Cytoplasm.

Tissue specificity. Expressed in nasal tissue.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P59827-1	1	yes
P59827-2	2

RefSeq proteins (1): NP_872325* (*=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
IPR051660	BPI_fold-BPI/LBP	Family

Pfam: PF01273, PF02886

UniProt features (13 total): sequence variant 8, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59827-F1	68.95	0.31

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): 295–332

Glycosylation sites (1): 273

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: 18 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, PAX4_01, chr20q11, YOSHIMURA_MAPK8_TARGETS_DN, GOMF_LIPID_BINDING, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_ANTIMICROBIAL_PEPTIDES, CBX5_TARGET_GENES, IGLV5_37_TARGET_GENES, MIR3202, MIR4294, HAY_BONE_MARROW_STROMAL, DURANTE_ADULT_OLFACTORY_NEUROEPITHELIUM_BOWMANS_GLAND, DESCARTES_MAIN_FETAL_LENS_FIBRE_CELLS, GSE9988_LPS_VS_LOW_LPS_MONOCYTE_DN

GO Biological Process (0):

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

GO Cellular Component (4): extracellular region (GO:0005576), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), cytoplasm (GO:0005737)

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
cellular anatomical structure	3
binding	1
cytoplasm	1
cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFB4	BPIFA1	Q9NP55	742
BPIFB4	BPIFA3	Q9BQP9	742
BPIFB4	BPIFA2	Q96DR5	734
BPIFB4	SCGB1C1	Q8TD33	531
BPIFB4	BPIFB1	Q8TDL5	503
BPIFB4	LCN15	Q6UWW0	426
BPIFB4	OBP2B	Q9NPH6	412
BPIFB4	A0A2R8Y455	A0A2R8Y455	411
BPIFB4	CLDND2	Q8NHS1	397
BPIFB4	COMMD7	Q86VX2	393
BPIFB4	LY86	O95711	389
BPIFB4	Q5T8A5	Q5T8A5	383
BPIFB4	GPNMB	Q14956	374
BPIFB4	CAMK4	Q16566	372
BPIFB4	CSMD2	Q7Z408	369

IntAct

0 interactions, top by confidence:

BioGRID (2): BPIFB4 (Affinity Capture-MS), BPIFB4 (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: A2BGH0, P59826, P59827, Q05701, Q05704, Q80ZU7, Q8NFQ5, Q8BU51

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2298 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33081630:ATGG:A	donor_loss	1.0000
20:33081631:TGGTG:T	donor_loss	1.0000
20:33081632:GGTG:G	donor_loss	1.0000
20:33081633:GT:G	donor_loss	1.0000
20:33084994:GAG:G	donor_gain	1.0000
20:33084996:GGTG:G	donor_loss	1.0000
20:33084997:G:GA	donor_loss	1.0000
20:33086008:T:A	acceptor_gain	1.0000
20:33086009:G:A	acceptor_gain	1.0000
20:33086017:CCA:C	acceptor_loss	1.0000
20:33086018:CAGT:C	acceptor_loss	1.0000
20:33086019:A:AG	acceptor_gain	1.0000
20:33086019:AGTC:A	acceptor_loss	1.0000
20:33086020:G:GT	acceptor_gain	1.0000
20:33086020:GT:G	acceptor_gain	1.0000
20:33086020:GTC:G	acceptor_gain	1.0000
20:33086020:GTCT:G	acceptor_gain	1.0000
20:33086020:GTCTT:G	acceptor_gain	1.0000
20:33086161:GAGG:G	donor_gain	1.0000
20:33086163:GG:G	donor_gain	1.0000
20:33086164:GG:G	donor_gain	1.0000
20:33086165:G:GA	donor_loss	1.0000
20:33086165:G:GG	donor_gain	1.0000
20:33086166:T:A	donor_loss	1.0000
20:33088964:A:AG	acceptor_gain	1.0000
20:33088965:G:GG	acceptor_gain	1.0000
20:33089496:A:AG	acceptor_gain	1.0000
20:33089497:G:GG	acceptor_gain	1.0000
20:33089497:GCTC:G	acceptor_gain	1.0000
20:33089497:GCTCT:G	acceptor_gain	1.0000

AlphaMissense

3929 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33086121:T:C	C295R	0.996
20:33086122:G:A	C295Y	0.996
20:33086064:G:C	A276P	0.995
20:33090762:C:G	P369R	0.995
20:33086121:T:A	C295S	0.994
20:33086122:G:C	C295S	0.994
20:33086123:T:G	C295W	0.994
20:33089501:T:A	C332S	0.994
20:33089501:T:C	C332R	0.994
20:33089502:G:C	C332S	0.994
20:33090762:C:A	P369Q	0.994
20:33090795:T:C	L380P	0.994
20:33084950:G:C	G246R	0.992
20:33084984:T:A	I257N	0.992
20:33089502:G:A	C332Y	0.992
20:33097773:T:C	C519R	0.992
20:33084990:G:A	G259E	0.990
20:33086107:T:C	L290P	0.990
20:33090783:T:C	L376P	0.990
20:33100469:T:C	L538P	0.990
20:33107768:T:A	L590H	0.990
20:33084960:T:C	L249P	0.989
20:33086122:G:T	C295F	0.989
20:33089503:C:G	C332W	0.989
20:33090738:T:A	V361D	0.989
20:33092573:T:C	L420P	0.989
20:33100469:T:A	L538H	0.989
20:33107771:C:A	P591H	0.989
20:33084995:A:C	S261R	0.988
20:33086021:T:A	S261R	0.988

dbSNP variants (sampled 300 via entrez): RS1000128675 (20:33103406 C>T), RS1000160426 (20:33091520 C>T), RS1000175630 (20:33109578 C>T), RS1000331086 (20:33080979 A>G), RS1000493677 (20:33090198 T>C), RS1000534692 (20:33107168 C>A,T), RS1000667984 (20:33079552 C>T), RS1000729115 (20:33085860 G>A), RS1000778360 (20:33081522 C>G,T), RS1000780479 (20:33079713 C>T), RS1000862736 (20:33101505 C>T), RS1000893672 (20:33101180 G>A,C), RS1000903859 (20:33086446 A>T), RS1001046108 (20:33089894 A>G), RS1001147689 (20:33092273 C>A,G,T)

Disease associations

OMIM: gene MIM:615718 | 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
GCST007258_1	Non-steroidal anti-inflammatory drug-induced enteropathy	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005533	response to non-steroidal anti-inflammatory
EFO:0009705	small intestine enteropathy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	decreases expression	1
bisphenol S	decreases expression	1
Troglitazone	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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