BPIFA2

Summary

BPIFA2 (BPI fold containing family A member 2, HGNC:16203) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family A member 2 (Q96DR5). Has strong antibacterial activity against P.aeruginosa.

This gene encodes a member of the palate, lung and nasal epithelium clone (Plunc) family of proteins. Members of this family have been proposed to play a role in the local antibacterial response in nose, mouth and upper respiratory pathways. The encoded soluble salivary protein binds bacterial lipopolysaccharide (LPS) and inhibits bacterial growth. This gene is present in a gene cluster on chromosome 20. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 140683 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_080574

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16203
Approved symbol	BPIFA2
Name	BPI fold containing family A member 2
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	bA49G10.1, SPLUNC2, PSP
Ensembl gene	ENSG00000131050
Ensembl biotype	protein_coding
OMIM	621166
Entrez	140683

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000253362, ENST00000354932

RefSeq mRNA: 2 — MANE Select: NM_080574 NM_001319164, NM_080574

CCDS: CCDS13214

Canonical transcript exons

ENST00000354932 — 9 exons

Exon	Start	End
ENSE00000898449	33169131	33169302
ENSE00000898450	33175407	33175559
ENSE00000991603	33172932	33173076
ENSE00000991604	33174079	33174186
ENSE00000991605	33178147	33178228
ENSE00000991606	33179604	33179667
ENSE00000991607	33180520	33180597
ENSE00001467180	33181224	33181412
ENSE00001530670	33168159	33168209

Expression profiles

Bgee: expression breadth broad, 66 present calls, max score 99.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 46.0587 / max 47635.0429, expressed in 20 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184096	45.1446	11
184097	0.2140	3
184093	0.1438	3
184100	0.1210	6
184101	0.0861	3
184095	0.0719	3
184102	0.0703	4
184099	0.0446	4
184120	0.0422	10
184094	0.0328	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.97	gold quality
nasal cavity epithelium	UBERON:0005384	85.57	silver quality
left ventricle myocardium	UBERON:0006566	84.37	gold quality
cardiac muscle of right atrium	UBERON:0003379	84.35	gold quality
pancreatic ductal cell	CL:0002079	81.34	silver quality
tongue	UBERON:0001723	75.74	gold quality
kidney epithelium	UBERON:0004819	75.64	gold quality
body of tongue	UBERON:0011876	74.66	gold quality
myocardium	UBERON:0002349	73.36	gold quality
ileal mucosa	UBERON:0000331	71.34	gold quality
tibialis anterior	UBERON:0001385	70.81	silver quality
sperm	CL:0000019	69.89	silver quality
upper arm skin	UBERON:0004263	69.78	gold quality
superior surface of tongue	UBERON:0007371	69.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	68.11	gold quality
epithelial cell of pancreas	CL:0000083	67.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.02	gold quality
buccal mucosa cell	CL:0002336	65.70	gold quality
quadriceps femoris	UBERON:0001377	64.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.13	gold quality
vastus lateralis	UBERON:0001379	62.78	gold quality
deltoid	UBERON:0001476	62.04	silver quality
cerebellar vermis	UBERON:0004720	62.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.46	gold quality
nasal cavity mucosa	UBERON:0001826	60.45	gold quality
epithelium of nasopharynx	UBERON:0001951	60.20	gold quality
vena cava	UBERON:0004087	59.65	gold quality
cardia of stomach	UBERON:0001162	59.36	gold quality
superficial temporal artery	UBERON:0001614	57.55	gold quality
trachea	UBERON:0003126	55.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	11.54
E-ANND-3	yes	3.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting BPIFA2, 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-5193	100.00	67.26	1744
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-4784	99.15	67.41	1733
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 2)

• multiple SPLUNC2 isoforms are found in the oral cavity and suggest that these proteins may be differentially regulated in distinct tissues where they may function in the innate immune response. (PMID:19499239)
• PSP is a lipopolysaccharide-binding protein that is functionally related to lipopolysaccharide-binding protein, as suggested by their predicted structural similarities (PMID:21833535)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifa2	ENSMUSG00000042459
rattus_norvegicus	Bpifa2	ENSRNOG00000013540
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

BPI fold-containing family A member 2 — Q96DR5 (reviewed: Q96DR5)

Alternative names: Parotid secretory protein, Short palate, lung and nasal epithelium carcinoma-associated protein 2

All UniProt accessions (1): Q96DR5

UniProt curated annotations — full annotation on UniProt →

Function. Has strong antibacterial activity against P.aeruginosa.

Subcellular location. Secreted.

Tissue specificity. Detected in submandibular gland. Secreted into saliva.

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

RefSeq proteins (2): NP_001306093, NP_542141* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017942	Lipid-bd_serum_glycop_N	Domain
IPR017943	Bactericidal_perm-incr_a/b_dom	Homologous_superfamily
IPR052507	BPI_fold-antibacterial	Family

Pfam: PF01273

UniProt features (9 total): sequence variant 3, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DR5-F1	65.37	0.05

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): 174–217

Glycosylation sites (2): 124, 132

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: 50 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, TGACCTY_ERR1_Q2, COUP_01, HNF4_DR1_Q3, chr20q11, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_5, GOCC_SECRETORY_VESICLE, GOMF_LIPOPOLYSACCHARIDE_BINDING, COUP_DR1_Q6, GOBP_RESPONSE_TO_BACTERIUM, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_LIPID_BINDING, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS

GO Biological Process (1): defense response to bacterium (GO:0042742)

GO Molecular Function (3): lipopolysaccharide binding (GO:0001530), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), secretory granule (GO:0030141), extracellular exosome (GO:0070062)

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	2
defense response	1
response to bacterium	1
lipid binding	1
carbohydrate derivative binding	1
cellular anatomical structure	1
endomembrane system	1
secretory vesicle	1
extracellular vesicle	1

Protein interactions and networks

STRING

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFA2	CA6	P23280	770
BPIFA2	BPIFB4	P59827	734
BPIFA2	BPIFB1	Q8TDL5	697
BPIFA2	LBP	P18428	642
BPIFA2	BPI	P17213	609
BPIFA2	BPIFA3	Q9BQP9	608
BPIFA2	BPIFB2	Q8N4F0	582
BPIFA2	BPIFB3	P59826	582
BPIFA2	BPIFB6	Q8NFQ5	538
BPIFA2	PIP	P12273	507
BPIFA2	CST1	P01037	475
BPIFA2	KIF22	Q14807	453
BPIFA2	BPIFA1	Q9NP55	450
BPIFA2	CST4	P01036	419
BPIFA2	CLDND2	Q8NHS1	415

IntAct

152 interactions, top by confidence:

A	B	Type	Score
UQCRQ	COX7A2L	psi-mi:“MI:0914”(association)	0.640
BPIFA2	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	BPIFA2	psi-mi:“MI:0915”(physical association)	0.560
BPIFA2	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
RHOBTB1	CST4	psi-mi:“MI:0914”(association)	0.530
PLEKHG6	CST4	psi-mi:“MI:0914”(association)	0.530
ZNF491	CST4	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
ACAD9	PPL	psi-mi:“MI:0914”(association)	0.530
KIR2DS2	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
BPIFA2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	BPIFA2	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
DLG4	BPIFA2	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (39): BPIFA2 (Two-hybrid), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), BPIFA2 (Two-hybrid), AGTRAP (Two-hybrid), BPIFA2 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS)

ESM2 similar proteins: A0JPN3, A2BGH0, E9Q414, F6KSY2, G3HIK4, O42273, P04114, P07743, P11597, P17454, P22687, P25914, P47896, P55058, P55065, P59826, P59827, P79124, P79125, P82615, P97361, Q05701, Q05704, Q10011, Q2TBI0, Q3V6R6, Q61114, Q61805, Q63313, Q63471, Q63751, Q67E05, Q6AXU0, Q7TMA5, Q80ZU7, Q865V1, Q86YQ2, Q8BU51, Q8C186, Q8C1E1

Diamond homologs: P07743, P79124, Q63471, Q96DR5, P79125

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	40.2×	9e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	38.3×	9e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	38.3×	9e-06
Assembly and cell surface presentation of NMDA receptors	10	35.7×	2e-11
Dopamine Neurotransmitter Release Cycle	5	35.0×	1e-05
Long-term potentiation	5	33.5×	1e-05
Neurexins and neuroligins	11	30.5×	2e-11
Protein-protein interactions at synapses	7	26.2×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	51.8×	5e-11
protein localization to synapse	6	45.5×	8e-07
receptor clustering	7	43.3×	8e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	29.4×	1e-05
cell-cell adhesion	8	8.0×	7e-04
protein-containing complex assembly	7	7.9×	2e-03
chemical synaptic transmission	8	6.1×	3e-03
protein transport	10	4.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

946 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33169298:TAAAG:T	donor_loss	1.0000
20:33169299:AAAG:A	donor_loss	1.0000
20:33169300:AAGGT:A	donor_loss	1.0000
20:33169302:GGT:G	donor_loss	1.0000
20:33169303:GTAA:G	donor_loss	1.0000
20:33169304:T:G	donor_loss	1.0000
20:33172926:TGGCA:T	acceptor_loss	1.0000
20:33172927:GGCA:G	acceptor_loss	1.0000
20:33172928:GCA:G	acceptor_loss	1.0000
20:33172929:CAGG:C	acceptor_loss	1.0000
20:33172930:A:AG	acceptor_gain	1.0000
20:33172930:A:AT	acceptor_loss	1.0000
20:33172931:G:GA	acceptor_loss	1.0000
20:33172931:G:GG	acceptor_gain	1.0000
20:33172931:GGC:G	acceptor_gain	1.0000
20:33173012:G:GT	donor_gain	1.0000
20:33173077:G:GG	donor_gain	1.0000
20:33174182:GCCGG:G	donor_gain	1.0000
20:33174184:CGGG:C	donor_loss	1.0000
20:33174185:GG:G	donor_gain	1.0000
20:33174185:GGGTG:G	donor_loss	1.0000
20:33174186:GG:G	donor_gain	1.0000
20:33174186:GGTG:G	donor_loss	1.0000
20:33174187:GTGA:G	donor_loss	1.0000
20:33174188:T:A	donor_loss	1.0000
20:33175401:CTGCA:C	acceptor_loss	1.0000
20:33175402:TGCA:T	acceptor_loss	1.0000
20:33175403:GCA:G	acceptor_loss	1.0000
20:33175404:CAG:C	acceptor_loss	1.0000
20:33175405:A:AG	acceptor_gain	1.0000

AlphaMissense

1630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33175516:T:A	C174S	0.964
20:33175517:G:C	C174S	0.964
20:33179607:T:C	C217R	0.962
20:33175516:T:C	C174R	0.961
20:33174167:G:C	A131P	0.960
20:33175463:T:A	V156D	0.947
20:33175433:T:C	L146P	0.933
20:33174162:T:A	V129D	0.932
20:33179609:T:G	C217W	0.932
20:33179608:G:A	C217Y	0.928
20:33175451:T:C	L152P	0.927
20:33174174:T:A	V133D	0.925
20:33179607:T:A	C217S	0.925
20:33179608:G:C	C217S	0.925
20:33174150:T:C	L125P	0.922
20:33175441:T:C	S149P	0.905
20:33175518:C:G	C174W	0.892
20:33175517:G:A	C174Y	0.886
20:33169176:T:C	C11R	0.881
20:33172987:G:C	W71C	0.870
20:33172987:G:T	W71C	0.870
20:33178194:T:C	L204P	0.867
20:33174144:T:C	L123P	0.865
20:33175439:C:A	A148D	0.862
20:33175451:T:A	L152H	0.860
20:33174168:C:A	A131E	0.859
20:33174150:T:A	L125Q	0.858
20:33169158:T:A	W5R	0.854
20:33169158:T:C	W5R	0.854
20:33175451:T:G	L152R	0.848

dbSNP variants (sampled 300 via entrez): RS1000008062 (20:33163458 G>T), RS1000027593 (20:33169165 T>C), RS1000173478 (20:33171897 C>A,T), RS1000364907 (20:33160125 T>C), RS1000393755 (20:33166131 T>G), RS1000510873 (20:33170405 T>C), RS1000612025 (20:33164551 C>T), RS1000818803 (20:33180854 G>A), RS1000890183 (20:33161206 C>T), RS1000932944 (20:33181144 A>G), RS1001009282 (20:33175781 A>G), RS1001119951 (20:33170574 TG>T), RS1001164377 (20:33173012 G>A,C), RS1001403893 (20:33161452 G>A,T), RS1001566152 (20:33175971 G>A)

Disease associations

OMIM: gene MIM:621166 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000853_7	Ulcerative colitis	4.000000e-06
GCST002361_12	Smooth-surface caries	3.000000e-06
GCST006585_2457	Blood protein levels	2.000000e-08
GCST90002390_695	Mean corpuscular hemoglobin	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

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	decreases expression, increases methylation	2
Calcitriol	decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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