BPIFC

Summary

BPIFC (BPI fold containing family C, HGNC:16503) is a protein-coding gene on chromosome 22q12.3, encoding BPI fold-containing family C protein (Q8NFQ6).

Predicted to enable lipopolysaccharide binding activity and phospholipid binding activity. Predicted to be involved in defense response to Gram-negative bacterium and innate immune response. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 254240 — RefSeq curated summary.

At a glance

• Gene–disease (curated): trichilemmal cyst (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_174932

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16503
Approved symbol	BPIFC
Name	BPI fold containing family C
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	dJ149A16.7
Ensembl gene	ENSG00000184459
Ensembl biotype	protein_coding
OMIM	614109
Entrez	254240

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000300399, ENST00000397450, ENST00000397452, ENST00000534972

RefSeq mRNA: 1 — MANE Select: NM_174932 NM_174932

CCDS: CCDS13906

Canonical transcript exons

ENST00000300399 — 17 exons

Exon	Start	End
ENSE00001109430	32432373	32432543
ENSE00001109432	32419362	32419404
ENSE00001109433	32431347	32431414
ENSE00001308590	32417085	32417148
ENSE00001315950	32415915	32415991
ENSE00001324245	32433719	32433772
ENSE00001528718	32461574	32461661
ENSE00003497126	32445841	32445996
ENSE00003606192	32453383	32453503
ENSE00003688112	32445635	32445698
ENSE00003691364	32447212	32447340
ENSE00003716064	32442671	32442731
ENSE00003719159	32437760	32437851
ENSE00003721370	32435704	32435880
ENSE00003757955	32457263	32457386
ENSE00003927119	32413845	32414425
ENSE00003938421	32464374	32464446

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 95.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0668 / max 18.3021, expressed in 21 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193748	0.0668	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	95.14	gold quality
skin of abdomen	UBERON:0001416	91.32	gold quality
zone of skin	UBERON:0000014	90.86	gold quality
skin of leg	UBERON:0001511	90.32	gold quality
mammalian vulva	UBERON:0000997	88.78	gold quality
skin of hip	UBERON:0001554	88.29	gold quality
gingival epithelium	UBERON:0001949	86.51	gold quality
gingiva	UBERON:0001828	86.42	gold quality
penis	UBERON:0000989	84.89	gold quality
sperm	CL:0000019	84.00	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.48	gold quality
nipple	UBERON:0002030	79.19	gold quality
islet of Langerhans	UBERON:0000006	78.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.91	gold quality
body of tongue	UBERON:0011876	63.77	silver quality
tongue	UBERON:0001723	59.16	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.88	gold quality
lateral globus pallidus	UBERON:0002476	57.46	gold quality
left testis	UBERON:0004533	55.94	gold quality
right testis	UBERON:0004534	55.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	55.42	gold quality
testis	UBERON:0000473	55.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	54.89	gold quality
pharyngeal mucosa	UBERON:0000355	53.68	gold quality
superior surface of tongue	UBERON:0007371	53.63	gold quality
buccal mucosa cell	CL:0002336	53.51	gold quality
dorsal plus ventral thalamus	UBERON:0001897	53.04	gold quality
ventral tegmental area	UBERON:0002691	52.86	gold quality
subthalamic nucleus	UBERON:0001906	52.82	gold quality
layer of synovial tissue	UBERON:0007616	52.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting BPIFC, 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-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-499B-5P	98.35	68.39	988

Literature-anchored findings (GeneRIF, showing 3)

• BPIL2maps to Chr 22q13. AA sequence is reported. (PMID:12185532)
• BPIFC c.3G>C mutation segregates with hereditary trichilemmal cysts in a large Chinese family. (PMID:31033252)
• Transcriptomic Analyses and Experimental Validation Identified Immune-Related lncRNA-mRNA Pair MIR210HG-BPIFC Regulating the Progression of Hypertrophic Cardiomyopathy. (PMID:38474063)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifc	ENSMUSG00000050108
rattus_norvegicus	Bpifc	ENSRNOG00000022937

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

BPI fold-containing family C protein — Q8NFQ6 (reviewed: Q8NFQ6)

Alternative names: Bactericidal/permeability-increasing protein-like 2

All UniProt accessions (3): Q8NFQ6, A0A8C8NLL8, Q5TI88

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Detected in the basal layer of the epidermis from inflammatory skin from psoriasis patients, but not in normal skin.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NFQ6-1	1	yes
Q8NFQ6-2	2

RefSeq proteins (1): NP_777592* (*=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
IPR017954	Lipid-bd_serum_glycop_CS	Conserved_site
IPR030675	BPI/LBP	Family
IPR032942	BPI/LBP/Plunc	Family

Pfam: PF01273, PF02886

UniProt features (19 total): glycosylation site 10, sequence variant 4, splice variant 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFQ6-F1	82.60	0.51

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): 161–200

Glycosylation sites (10): 372, 415, 79, 92, 113, 213, 225, 257, 301, 355

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_LIPOPOLYSACCHARIDE_BINDING, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, MIKKELSEN_MCV6_LCP_WITH_H3K27ME3, CHYLA_CBFA2T3_TARGETS_UP, LHX9_TARGET_GENES, MIR570_3P, MIR5688, MIR495_3P, MIR4755_5P, MIR5006_3P, MIR513B_5P, MIR6783_3P

GO Biological Process (4): innate immune response (GO:0045087), immune system process (GO:0002376), defense response to bacterium (GO:0042742), defense response to Gram-negative bacterium (GO:0050829)

GO Molecular Function (3): lipopolysaccharide binding (GO:0001530), phospholipid binding (GO:0005543), lipid binding (GO:0008289)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid binding	2
immune response	1
defense response to symbiont	1
biological_process	1
defense response	1
response to bacterium	1
defense response to bacterium	1
carbohydrate derivative binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFC	TMEM239	Q8WW34	591
BPIFC	WFDC12	Q8WWY7	498
BPIFC	DEFB115	Q30KQ5	492
BPIFC	DRC10	Q96DY2	478
BPIFC	DEFB128	Q7Z7B8	471
BPIFC	PGLYRP3	Q96LB9	428
BPIFC	BPIFA1	Q9NP55	410
BPIFC	CALHM4	Q5JW98	400
BPIFC	FHIP2B	Q86V87	385
BPIFC	PLEKHA4	Q9H4M7	383
BPIFC	RFPL3	O75679	370
BPIFC	INKA1	Q96EL1	354
BPIFC	BPIFA2	Q96DR5	350
BPIFC	RFPL2	O75678	349
BPIFC	BPIFB1	Q8TDL5	343

IntAct

4 interactions, top by confidence:

A	B	Type	Score
BPIFC	METTL21C	psi-mi:“MI:0915”(physical association)	0.400
BPIFC	HSPA2	psi-mi:“MI:0915”(physical association)	0.400
	POLRMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): METTL21C (Affinity Capture-MS), HSPA2 (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: A0A481NSZ4, P17213, P17453, P18428, Q28739, Q2TBI0, Q61805, Q63313, Q8NFQ6, Q8C186

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1792 predictions. Top by Δscore:

Variant	Effect	Δscore
22:32417147:ACCTA:A	acceptor_loss	1.0000
22:32417148:CCTAA:C	acceptor_loss	1.0000
22:32417149:C:CA	acceptor_loss	1.0000
22:32417149:C:CC	acceptor_gain	1.0000
22:32417150:T:A	acceptor_loss	1.0000
22:32432371:A:AC	donor_gain	1.0000
22:32432372:C:CT	donor_gain	1.0000
22:32432549:C:CT	acceptor_gain	1.0000
22:32432549:C:T	acceptor_gain	1.0000
22:32432552:A:C	acceptor_gain	1.0000
22:32432556:C:CT	acceptor_gain	1.0000
22:32432556:C:T	acceptor_gain	1.0000
22:32432557:G:T	acceptor_gain	1.0000
22:32435877:CACC:C	acceptor_gain	1.0000
22:32435879:CC:C	acceptor_gain	1.0000
22:32435880:CCTG:C	acceptor_gain	1.0000
22:32437847:TAAAA:T	acceptor_gain	1.0000
22:32437852:C:CC	acceptor_gain	1.0000
22:32437862:A:T	acceptor_gain	1.0000
22:32447210:A:AC	donor_gain	1.0000
22:32447211:C:CC	donor_gain	1.0000
22:32453381:A:AC	donor_gain	1.0000
22:32453382:C:CC	donor_gain	1.0000
22:32453500:ACAC:A	acceptor_gain	1.0000
22:32453501:CAC:C	acceptor_gain	1.0000
22:32453501:CACC:C	acceptor_gain	1.0000
22:32453502:AC:A	acceptor_gain	1.0000
22:32453502:ACCT:A	acceptor_loss	1.0000
22:32453503:CC:C	acceptor_gain	1.0000
22:32453503:CCTG:C	acceptor_loss	1.0000

AlphaMissense

3333 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:32432437:G:T	A362D	0.966
22:32432449:A:G	L358P	0.964
22:32432435:A:G	S363P	0.960
22:32431366:A:G	C400R	0.955
22:32431410:G:T	A385D	0.953
22:32431398:A:T	V389D	0.950
22:32432438:C:G	A362P	0.947
22:32419401:G:C	F407L	0.927
22:32419401:G:T	F407L	0.927
22:32419403:A:G	F407L	0.927
22:32445973:A:G	L133P	0.926
22:32417090:G:T	A440D	0.923
22:32435743:G:C	F295L	0.922
22:32435743:G:T	F295L	0.922
22:32435745:A:G	F295L	0.922
22:32435880:C:G	G250R	0.922
22:32447234:A:G	W118R	0.919
22:32447234:A:T	W118R	0.919
22:32419402:A:G	F407S	0.917
22:32431411:C:G	A385P	0.915
22:32447252:C:G	A112P	0.915
22:32442727:C:G	C200S	0.914
22:32442728:A:T	C200S	0.914
22:32414418:A:G	L470P	0.909
22:32435763:A:G	S289P	0.907
22:32431359:A:G	L402S	0.900
22:32435750:G:T	A293D	0.898
22:32435759:G:T	A290E	0.898
22:32442728:A:G	C200R	0.898
22:32432449:A:C	L358R	0.895

dbSNP variants (sampled 300 via entrez): RS1000126898 (22:32454912 G>T), RS1000129456 (22:32437909 T>C), RS1000156191 (22:32433194 C>A,G), RS1000180088 (22:32416834 C>A,G), RS1000183670 (22:32438285 A>T), RS1000232617 (22:32417169 G>A,C), RS1000388931 (22:32419195 T>C), RS1000426214 (22:32444245 G>T), RS1000508269 (22:32454326 A>G), RS1000614540 (22:32459807 T>A,C), RS1000790726 (22:32432752 G>A,T), RS1000844502 (22:32464914 C>T), RS1000881881 (22:32443943 A>G), RS1000897198 (22:32460776 G>A,T), RS1000961418 (22:32454053 G>A,C)

Disease associations

OMIM: gene MIM:614109 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
trichilemmal cyst	Limited	Autosomal dominant

Mondo (1): trichilemmal cyst (MONDO:0012328)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_81	Refractive error	6.000000e-13

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
sodium arsenate	increases abundance, decreases expression	1
hydroquinone	increases expression	1
abrine	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Tetrachlorodibenzodioxin	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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