BPIFB6

Summary

BPIFB6 (BPI fold containing family B member 6, HGNC:16504) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family B member 6 (Q8NFQ5).

Predicted to enable lipid binding activity. Predicted to be located in extracellular region.

Source: NCBI Gene 128859 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_174897

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16504
Approved symbol	BPIFB6
Name	BPI fold containing family B member 6
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	LPLUNC6
Ensembl gene	ENSG00000167104
Ensembl biotype	protein_coding
OMIM	614110
Entrez	128859

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000349552, ENST00000542375, ENST00000850977

RefSeq mRNA: 1 — MANE Select: NM_174897 NM_174897

CCDS: CCDS13211

Canonical transcript exons

ENST00000349552 — 15 exons

Exon	Start	End
ENSE00001254403	33032984	33033083
ENSE00003459574	33039347	33039520
ENSE00003472775	33034186	33034290
ENSE00003486352	33040251	33040318
ENSE00003539403	33043291	33043367
ENSE00003539818	33036445	33036536
ENSE00003565157	33037562	33037738
ENSE00003567763	33041970	33042015
ENSE00003575819	33035081	33035144
ENSE00003608611	33035612	33035672
ENSE00003625357	33042815	33042878
ENSE00003657279	33034763	33034912
ENSE00003663822	33038909	33038962
ENSE00004283115	33044015	33044047
ENSE00004283117	33031648	33031744

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 58.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2310 / max 120.1050, expressed in 31 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184081	0.0979	26
184083	0.0643	21
184085	0.0304	6
184078	0.0139	5
184079	0.0075	4
184080	0.0067	3
184082	0.0053	4
184084	0.0051	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	58.79	gold quality
superior surface of tongue	UBERON:0007371	56.87	gold quality
minor salivary gland	UBERON:0001830	52.10	gold quality
nasal cavity mucosa	UBERON:0001826	51.41	gold quality
mouth mucosa	UBERON:0003729	50.54	gold quality
saliva-secreting gland	UBERON:0001044	49.64	gold quality
tongue	UBERON:0001723	49.22	silver quality
trachea	UBERON:0003126	47.14	gold quality
body of tongue	UBERON:0011876	43.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
pharyngeal mucosa	UBERON:0000355	42.32	gold quality
colonic epithelium	UBERON:0000397	42.01	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.12

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• BPIL3 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)
• study reports on the cellular function of BPIFB6 in the regulation of secretory pathway trafficking and Golgi complex morphology; in addition, findings show that BPIFB6 functions as a positive regulator of enterovirus replication via its regulation of the secretory pathway (PMID:26962226)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifb6	ENSMUSG00000068009
rattus_norvegicus	Bpifb6	ENSRNOG00000013371
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

BPI fold-containing family B member 6 — Q8NFQ5 (reviewed: Q8NFQ5)

Alternative names: Bactericidal/permeability-increasing protein-like 3

All UniProt accessions (2): Q8NFQ5, F5H8I3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Detected at very low levels in normal tonsils, and at higher levels in hypertrophic tonsils.

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

RefSeq proteins (1): NP_777557* (*=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 (10 total): sequence variant 5, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFQ5-F1	88.20	0.63

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): 137–174

Glycosylation sites (2): 114, 190

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: 16 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, chr20q11, GOMF_LIPID_BINDING, MARTENS_TRETINOIN_RESPONSE_UP, REACTOME_ANTIMICROBIAL_PEPTIDES, ZFP91_TARGET_GENES, GSE15659_NAIVE_VS_PTPRC_NEG_CD4_TCELL_UP, GSE15659_NAIVE_CD4_TCELL_VS_NONSUPPRESSIVE_TCELL_UP, GSE15659_CD45RA_NEG_CD4_TCELL_VS_NONSUPPRESSIVE_TCELL_UP, GSE15659_RESTING_TREG_VS_NONSUPPRESSIVE_TCELL_UP, GSE15659_RESTING_VS_ACTIVATED_TREG_UP, GSE18791_UNSTIM_VS_NEWCATSLE_VIRUS_DC_1H_UP, TTF1_Q6, GSE18281_PERIMEDULLARY_CORTICAL_REGION_VS_WHOLE_MEDULLA_THYMUS_DN, GSE21546_UNSTIM_VS_ANTI_CD3_STIM_SAP1A_KO_AND_ELK1_KO_DP_THYMOCYTES_DN

GO Biological Process (0):

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

GO Cellular Component (1): extracellular region (GO:0005576)

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
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFB6	BPIFA3	Q9BQP9	676
BPIFB6	BPIFA1	Q9NP55	647
BPIFB6	BPIFB1	Q8TDL5	601
BPIFB6	BPIFA2	Q96DR5	538
BPIFB6	CIB4	A0PJX0	497
BPIFB6	A0A2R8Y455	A0A2R8Y455	488
BPIFB6	COMMD7	Q86VX2	473
BPIFB6	TTLL9	Q3SXZ7	408
BPIFB6	CCM2L	Q9NUG4	407
BPIFB6	BPIFB2	Q8N4F0	388
BPIFB6	SLX4IP	Q5VYV7	380
BPIFB6	LY86	O95711	364
BPIFB6	OTOP3	Q7RTS5	341
BPIFB6	GKN2	Q86XP6	337
BPIFB6	OBP2B	Q9NPH6	330

IntAct

2 interactions, top by confidence:

A	B	Type	Score
BPIFB6	HSPA5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): HSPA5 (Affinity Capture-MS), BPIFB6 (Cross-Linking-MS (XL-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2252 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33032982:A:AG	acceptor_gain	1.0000
20:33032983:G:GG	acceptor_gain	1.0000
20:33033080:CCAA:C	donor_gain	1.0000
20:33033083:AGT:A	donor_loss	1.0000
20:33033084:GTGA:G	donor_gain	1.0000
20:33033085:T:A	donor_loss	1.0000
20:33033086:GAG:G	donor_loss	1.0000
20:33034184:A:AG	acceptor_gain	1.0000
20:33034184:AGTTT:A	acceptor_gain	1.0000
20:33034185:G:GA	acceptor_gain	1.0000
20:33034185:GT:G	acceptor_gain	1.0000
20:33034185:GTT:G	acceptor_gain	1.0000
20:33034185:GTTT:G	acceptor_gain	1.0000
20:33034185:GTTTG:G	acceptor_gain	1.0000
20:33034288:GAG:G	donor_gain	1.0000
20:33034289:AGGT:A	donor_loss	1.0000
20:33034292:T:A	donor_loss	1.0000
20:33034859:GA:G	donor_gain	1.0000
20:33034861:G:GG	donor_gain	1.0000
20:33034865:GGGCT:G	donor_gain	1.0000
20:33034866:GGCTG:G	donor_gain	1.0000
20:33034909:GCAA:G	donor_gain	1.0000
20:33034913:G:GG	donor_gain	1.0000
20:33035026:A:AG	acceptor_gain	1.0000
20:33035027:A:G	acceptor_gain	1.0000
20:33035611:GATGT:G	acceptor_gain	1.0000
20:33035670:GTG:G	donor_gain	1.0000
20:33035671:TGG:T	donor_loss	1.0000
20:33035673:G:A	donor_loss	1.0000
20:33035673:G:GG	donor_gain	1.0000

AlphaMissense

2971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33034809:G:C	A117P	0.988
20:33034278:T:A	V97D	0.972
20:33034284:G:A	G99D	0.969
20:33035615:T:A	C174S	0.967
20:33035616:G:C	C174S	0.967
20:33035615:T:C	C174R	0.962
20:33035657:T:A	W188R	0.962
20:33035657:T:C	W188R	0.962
20:33039434:A:C	S330R	0.961
20:33039436:C:A	S330R	0.961
20:33039436:C:G	S330R	0.961
20:33034289:A:C	S101R	0.960
20:33034763:C:A	S101R	0.960
20:33034763:C:G	S101R	0.960
20:33034786:T:C	I109T	0.958
20:33034869:T:A	C137S	0.956
20:33034870:G:C	C137S	0.956
20:33034870:G:A	C137Y	0.951
20:33034869:T:C	C137R	0.949
20:33034764:T:C	F102L	0.948
20:33034766:C:A	F102L	0.948
20:33034766:C:G	F102L	0.948
20:33035107:T:C	F160S	0.939
20:33034786:T:G	I109S	0.938
20:33034244:G:C	G86R	0.936
20:33035106:T:C	F160L	0.936
20:33035108:C:A	F160L	0.936
20:33035108:C:G	F160L	0.936
20:33034855:T:C	F132S	0.935
20:33034810:C:A	A117D	0.934

dbSNP variants (sampled 300 via entrez): RS1000032714 (20:33030392 A>G), RS1000071650 (20:33038001 C>T), RS1000319663 (20:33035270 T>A,C), RS1000650197 (20:33034175 T>G), RS1000711242 (20:33042599 C>G), RS1000774404 (20:33043941 G>A,T), RS1001222259 (20:33042355 G>A,T), RS1002593096 (20:33031988 A>C,G), RS1003115236 (20:33033774 G>T), RS1003273375 (20:33040884 T>C), RS1003313642 (20:33032730 C>G,T), RS1003320821 (20:33041067 G>C,T), RS1003367264 (20:33030572 C>A), RS1003502233 (20:33036772 A>G), RS1003691080 (20:33042485 G>A)

Disease associations

OMIM: gene MIM:614110 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Fonofos	increases methylation	1
Formaldehyde	decreases expression	1
Parathion	increases methylation	1

Clinical trials (associated diseases)

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