BPIFB3

Summary

BPIFB3 (BPI fold containing family B member 3, HGNC:16178) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family B member 3 (P59826). May have the capacity to recognize and bind specific classes of odorants.

Predicted to enable lipid binding activity. Predicted to be involved in innate immune response. Located in cytoplasm.

Source: NCBI Gene 359710 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001376932

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16178
Approved symbol	BPIFB3
Name	BPI fold containing family B member 3
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ726C3.4, LPLUNC3, RYA3
Ensembl gene	ENSG00000186190
Ensembl biotype	protein_coding
OMIM	615717
Entrez	359710

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375494

RefSeq mRNA: 2 — MANE Select: NM_001376932 NM_001376932, NM_182658

CCDS: CCDS13212

Canonical transcript exons

ENST00000375494 — 16 exons

Exon	Start	End
ENSE00001331607	33072104	33072167
ENSE00001331608	33071253	33071295
ENSE00001331609	33069888	33069955
ENSE00001331612	33068803	33068973
ENSE00001331614	33066824	33066877
ENSE00001331617	33064666	33064845
ENSE00001331618	33064457	33064548
ENSE00001331619	33063615	33063675
ENSE00001331620	33061768	33061831
ENSE00001331669	33059891	33060031
ENSE00001331670	33059378	33059482
ENSE00001331671	33056542	33056698
ENSE00001433450	33072717	33072793
ENSE00001467253	33073576	33073847
ENSE00001467269	33055422	33055547
ENSE00003966068	33053903	33053965

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 94.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0103 / max 18.1283, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184090	0.0103	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	94.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.41	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.73	gold quality
adenohypophysis	UBERON:0002196	51.01	gold quality
pituitary gland	UBERON:0000007	50.22	gold quality
monocyte	CL:0000576	46.61	silver quality
leukocyte	CL:0000738	45.43	silver quality
right testis	UBERON:0004534	40.60	gold quality
testis	UBERON:0000473	39.37	gold quality
left testis	UBERON:0004533	38.99	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
granulocyte	CL:0000094	35.92	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
sural nerve	UBERON:0015488	35.35	gold quality
tonsil	UBERON:0002372	35.23	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
blood	UBERON:0000178	31.40	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
liver	UBERON:0002107	30.33	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.78	gold quality
urinary bladder	UBERON:0001255	28.82	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Overexpression of BPIFB3 inhibits coxsackievirus B replication, dramatically alters the morphology of LC3B-positive vesicles, and suppresses autophagy in response to rapamycin. (PMID:25491355)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifb3	ENSMUSG00000068008
rattus_norvegicus	Bpifb3	ENSRNOG00000075637
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), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

BPI fold-containing family B member 3 — P59826 (reviewed: P59826)

Alternative names: Ligand-binding protein RYA3, Long palate, lung and nasal epithelium carcinoma-associated protein 3

All UniProt accessions (1): P59826

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. Detected in nasal septal epithelium.

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

RefSeq proteins (2): NP_001363861, NP_872599 (=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 (11 total): sequence variant 5, glycosylation site 3, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59826-F1	81.71	0.38

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): 160–195

Glycosylation sites (3): 138, 284, 453

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, PTF1BETA_Q6, chr20q11, GOMF_LIPID_BINDING, ZNF92_TARGET_GENES, GSE8685_IL15_ACT_IL2_STARVED_VS_IL21_ACT_IL2_STARVED_CD4_TCELL_UP, GSE7568_IL4_VS_IL4_AND_TGFB_TREATED_MACROPHAGE_24H_DN, MANNE_COVID19_NONICU_VS_HEALTHY_DONOR_PLATELETS_DN, HAY_BONE_MARROW_PLATELET, ZNF623_TARGET_GENES, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERSPECIES_INTERACTION_BETWEEN_ORGANISMS, GSE19825_NAIVE_VS_IL2RALOW_DAY3_EFF_CD8_TCELL_UP, GSE19825_NAIVE_VS_IL2RAHIGH_DAY3_EFF_CD8_TCELL_UP, ZHANG_FH_DEFICIENT_RCC_C2_VS_OTHERS_UP, GSE36392_EOSINOPHIL_VS_MAC_IL25_TREATED_LUNG_UP

GO Biological Process (1): innate immune response (GO:0045087)

GO Molecular Function (2): lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
immune response	1
defense response to symbiont	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFB3	BPIFA3	Q9BQP9	679
BPIFB3	BPIFB1	Q8TDL5	592
BPIFB3	BPIFA1	Q9NP55	583
BPIFB3	BPIFA2	Q96DR5	582
BPIFB3	SCGB1C1	Q8TD33	573
BPIFB3	PCP4L1	A6NKN8	494
BPIFB3	TMEM192	Q8IY95	491
BPIFB3	SAXO2	Q658L1	453
BPIFB3	TEX261	Q6UWH6	449
BPIFB3	TTC16	Q8NEE8	446
BPIFB3	OR2B2	Q9GZK3	419
BPIFB3	SAXO5	Q8NA69	419
BPIFB3	ACSM4	P0C7M7	404
BPIFB3	TM4SF20	Q53R12	369
BPIFB3	INCA1	Q0VD86	368

IntAct

9 interactions, top by confidence:

A	B	Type	Score
BPIFB3	EVX2	psi-mi:“MI:0915”(physical association)	0.560
BPIFB3	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	BPIFB3	psi-mi:“MI:0915”(physical association)	0.400
STAT1	BPIFB3	psi-mi:“MI:0915”(physical association)	0.000
EVX2	BPIFB3	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	BPIFB3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): BPIFB3 (Affinity Capture-MS), BPIFB3 (Affinity Capture-MS), BPIFB3 (Co-fractionation), BPIFB3 (Two-hybrid), BPIFB3 (Two-hybrid)

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2163 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33055544:AAAGG:A	donor_loss	1.0000
20:33055547:GGTGA:G	donor_loss	1.0000
20:33059376:A:AG	acceptor_gain	1.0000
20:33059377:G:GA	acceptor_gain	1.0000
20:33059481:GG:G	donor_gain	1.0000
20:33059482:GG:G	donor_gain	1.0000
20:33059889:A:AG	acceptor_gain	1.0000
20:33059890:G:GC	acceptor_gain	1.0000
20:33059890:GCCCC:G	acceptor_gain	1.0000
20:33060030:GG:G	donor_gain	1.0000
20:33060031:GG:G	donor_gain	1.0000
20:33064549:G:GG	donor_gain	1.0000
20:33064661:T:TA	acceptor_gain	1.0000
20:33064661:TGCA:T	acceptor_loss	1.0000
20:33064663:CA:C	acceptor_loss	1.0000
20:33064664:A:AG	acceptor_gain	1.0000
20:33064665:G:GA	acceptor_gain	1.0000
20:33064665:G:GT	acceptor_loss	1.0000
20:33064665:GC:G	acceptor_gain	1.0000
20:33064665:GCC:G	acceptor_gain	1.0000
20:33064665:GCCT:G	acceptor_gain	1.0000
20:33064841:AGCTG:A	donor_gain	1.0000
20:33064842:GCTG:G	donor_gain	1.0000
20:33064842:GCTGG:G	donor_gain	1.0000
20:33064843:CTG:C	donor_gain	1.0000
20:33064844:TG:T	donor_gain	1.0000
20:33064844:TGG:T	donor_loss	1.0000
20:33064845:GG:G	donor_gain	1.0000
20:33064846:G:GG	donor_gain	1.0000
20:33066813:T:A	acceptor_gain	1.0000

AlphaMissense

2998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33064492:T:C	F230L	0.969
20:33064494:C:A	F230L	0.969
20:33064494:C:G	F230L	0.969
20:33055521:G:C	R33P	0.946
20:33073579:G:C	A469P	0.934
20:33073583:T:A	V470D	0.929
20:33072735:T:C	I448T	0.922
20:33064757:A:C	Q279P	0.920
20:33068897:T:A	V358D	0.918
20:33073589:T:C	L472P	0.918
20:33064781:T:C	F287S	0.912
20:33064493:T:C	F230S	0.904
20:33055518:C:A	A32D	0.894
20:33064538:T:C	L245P	0.893
20:33068870:T:A	V349D	0.893
20:33069931:T:C	L398P	0.886
20:33072744:C:A	P451H	0.883
20:33072764:T:C	F458L	0.883
20:33072766:T:A	F458L	0.883
20:33072766:T:G	F458L	0.883
20:33063618:T:C	C199R	0.875
20:33063618:T:A	C199S	0.871
20:33063619:G:C	C199S	0.871
20:33068921:T:A	V366E	0.869
20:33068966:T:C	L381P	0.868
20:33072126:T:C	L428P	0.868
20:33064766:T:A	V282E	0.865
20:33072124:G:C	W427C	0.859
20:33072124:G:T	W427C	0.859
20:33069931:T:G	L398R	0.857

dbSNP variants (sampled 300 via entrez): RS1000021762 (20:33069449 C>T), RS1000096673 (20:33065241 A>C,T), RS1000546398 (20:33053277 T>C), RS1000611793 (20:33054346 C>T), RS1000912701 (20:33063516 A>G), RS1001049521 (20:33069660 A>T), RS1001081063 (20:33054680 A>G,T), RS1001584581 (20:33060840 C>T), RS1001700652 (20:33061014 C>G), RS1001921747 (20:33059717 C>T), RS1001927833 (20:33066756 C>G,T), RS1002086819 (20:33055968 C>T), RS1002265378 (20:33060962 T>C), RS1002570143 (20:33053208 C>T), RS1002585895 (20:33061887 C>G,T)

Disease associations

OMIM: gene MIM:615717 | 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
GCST90013410_65	Basal cell carcinoma	2.000000e-12

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
Benzo(a)pyrene	affects methylation	2
bisphenol A	decreases methylation	1
aflatoxin B2	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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