BPI

Summary

BPI (bactericidal permeability increasing protein, HGNC:1095) is a protein-coding gene on chromosome 20q11.23, encoding Bactericidal permeability-increasing protein (P17213). The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope.

This gene encodes a lipopolysaccharide binding protein. It is associated with human neutrophil granules and has antimicrobial activity against gram-negative organisms.

Source: NCBI Gene 671 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_001725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1095
Approved symbol	BPI
Name	bactericidal permeability increasing protein
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	BPIFD1
Ensembl gene	ENSG00000101425
Ensembl biotype	protein_coding
OMIM	109195
Entrez	671

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262865, ENST00000417318, ENST00000418004, ENST00000451435, ENST00000489039, ENST00000489102, ENST00000490381, ENST00000642449, ENST00000716802, ENST00000948435

RefSeq mRNA: 1 — MANE Select: NM_001725 NM_001725

CCDS: CCDS13303

Canonical transcript exons

ENST00000642449 — 15 exons

Exon	Start	End
ENSE00000661935	38307567	38307681
ENSE00000661936	38308930	38309058
ENSE00000661937	38310491	38310652
ENSE00000661938	38311874	38311937
ENSE00000844629	38335598	38335674
ENSE00000906855	38323870	38324046
ENSE00001944087	38337146	38337505
ENSE00003545079	38320183	38320274
ENSE00003566212	38318413	38318476
ENSE00003614541	38334430	38334493
ENSE00003624066	38326265	38326432
ENSE00003631358	38324774	38324833
ENSE00004030758	38331048	38331090
ENSE00004030759	38304156	38304353
ENSE00004030761	38327588	38327655

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.5287 / max 2415.0122, expressed in 176 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184560	4.3336	106
184559	0.8221	115
184558	0.2944	54
184561	0.0517	4
184563	0.0167	3
184562	0.0101	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.17	gold quality
bone marrow	UBERON:0002371	98.76	gold quality
bone marrow cell	CL:0002092	97.79	gold quality
bone element	UBERON:0001474	96.15	gold quality
mononuclear cell	CL:0000842	88.27	gold quality
monocyte	CL:0000576	88.24	gold quality
leukocyte	CL:0000738	87.81	gold quality
left testis	UBERON:0004533	87.45	gold quality
right testis	UBERON:0004534	86.41	gold quality
sperm	CL:0000019	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.79	gold quality
granulocyte	CL:0000094	84.57	gold quality
testis	UBERON:0000473	84.08	gold quality
male germ cell	CL:0000015	83.68	silver quality
blood	UBERON:0000178	82.07	gold quality
spleen	UBERON:0002106	71.03	gold quality
adult organism	UBERON:0007023	67.41	gold quality
endocervix	UBERON:0000458	66.93	gold quality
right lung	UBERON:0002167	63.11	gold quality
descending thoracic aorta	UBERON:0002345	62.26	gold quality
adult mammalian kidney	UBERON:0000082	61.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.65	gold quality
ectocervix	UBERON:0012249	61.46	gold quality
right coronary artery	UBERON:0001625	61.11	gold quality
right ovary	UBERON:0002118	60.99	gold quality
left ovary	UBERON:0002119	59.78	gold quality
upper lobe of left lung	UBERON:0008952	57.75	gold quality
kidney epithelium	UBERON:0004819	57.60	silver quality
amniotic fluid	UBERON:0000173	57.32	silver quality
kidney	UBERON:0002113	57.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	6270.80
E-ANND-3	yes	5.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPE, CEBPG, IRX1, RUNX1, SP3, SPI1

miRNA regulators (miRDB)

24 targeting BPI, 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-4283	100.00	66.42	2097
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-3156-5P	96.93	67.36	800
HSA-MIR-6085	96.57	64.11	621
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-6813-5P	94.68	64.20	588

Literature-anchored findings (GeneRIF, showing 37)

• Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epithelia (PMID:11891303)
• increased levels in fetal disease, premature rupture of membranes, and preterm labor (PMID:12710851)
• Constitutive expression of BPI, which increases upon interleukin 4 stimulation, by human dermal fibroblast was demonstrated, suggesting an important role of BPI in gram-negative bacterial clearance and a dampened response to endotoxin in the skin (PMID:12738651)
• BPI and cathepsin G are the major antigenic targets of ANCA seen in patients with systemic sclerosis (PMID:12784398)
• BPI and HNP are accumulated in the synovial cavity of patients with rheumatoid arthritis (PMID:12913926)
• In conclusion, we provide evidence for AML-1, PU.1, and Sp3 cooperatively and directly mediating BPI-expression during myeloid differentiation. (PMID:14623259)
• BPI could exist in the inner root sheath cells of human and rat hair follicles, and might play a role as a barrier against anaerobic bacteria (PMID:15009116)
• The BPI stored in human neutrophil granulocytes, is cytotoxic against Gram-negative bacteria. (PMID:15590754)
• The bactericidal/permeability increasing protein (BPI) is involved in the elimination of gram-negative bacteria. A functionally relevant single nucleotide polymorphism of the BPI gene causes an amino acid exchange (Glu216Lys). (PMID:15758620)
• Studies of BPI promoter expression in intestinal epithelial cells identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. (PMID:16282362)
• findings suggest that BPI is associated with metabolic pathways (PMID:16380496)
• BPI that is functionally active against mucoid P. aeruginosa strains is expressed in the airways of Cystic Fibrosis patients but may be hampered by autoantibodies, resulting in chronic infection. (PMID:16861658)
• The present study does not give evidence for the contribution of the BPI gene to the genetic background of chronic periodontal disease. (PMID:16893388)
• BPI has unusual dual properties of promoting retinal pericytes and retinal pigment epithelial cell growth while suppressing VEGF-induced retinal epithelial cell growth and vascular permeability (PMID:17012258)
• Reduces expression of type I inetrferon by antagonizing lipopolysaccharide-binding protein. (PMID:17239348)
• the requirement for C/EBP epsilon in mediating BPI gene expression in myeloid cells in vitro and in vivo. (PMID:17483073)
• Restriction enzyme digestion and DNA sequence analysis revealed that the sequence encoding signal peptide and bioactive N-terminal fragment of BPI had six nucleotide substitutions, compared with that of the established human BPI sequence (PMID:17488601)
• a novel role of BPI in the interaction of bacterial outer membrane vesicles with dendritic cells that may help link innate immune recognition of endotoxin to Ag delivery and presentation. (PMID:17675509)
• This review article focuses on the structural and functional properties of BPI with respect to its antimicrobial contribution to host defense during GNB infections and endotoxin-induced inflammation. (PMID:17678885)
• evaluated the role of genetic polymorphisms of the bactericidal permeability increasing protein (BPI) in pediatric patients with sepsis (PMID:17898994)
• Investigated if serum and salivary anti-BPI autoantibodies appear in the course of acute pneumonia. Presence of anti-BPI IgG on admission didn’t correlate with inflammatory markers. Salivary anti-BPI IgA didn’t appear during the course of acute pneumonia. (PMID:19702878)
• Circulating BPI could constitute a biomarker of lipid metabolism in subjects with normal glucose tolerance and could help to identify those subjects with preserved endothelial function. (PMID:20174761)
• BPI is the main target antigen for ANCA in tuberculosis and BPI-ANCA increase after treatment (PMID:20412700)
• SNP Lys216Glu is associated with Crohn’s disease and ulcerative colities (PMID:21272798)
• there is a correlation between the presence of BPI-ANCA, the properties of the colonizing bacteria and the clinical conditions of the host in cystic fibrosis (PMID:21463973)
• The bactericidal/permeability-increasing protein in the innate defence of the lower airways (PMID:21787345)
• BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD…BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers. (PMID:22409502)
• Lung function and IgA-BPI-ANCA, but not Leeds criteria, were significantly associated with adverse outcome. (PMID:23346184)
• Diminished PRRs, IFN-signature, and BPI gene expression raises the possibility that impairments in these pathways contribute to the susceptibility of LBW term infants to infection. (PMID:23626859)
• MPO and BPI in CD4(+)T-lymphocytes, and PDHA1 and MRPL42 in CD8(+) T-lymphocytes might be used as specific biomarkers of severe asthma progression. (PMID:26107902)
• Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn’s disease and ulcerative colitis. (PMID:26228368)
• BPI G645A polymorphism was associated with a decreased risk of ulcerative colitis; the BPI G645A polymorphism was not associated with the risk of crohn’s disease. (PMID:28035462)
• define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections. (PMID:30581431)
• Serum BPI protein levels are associated with inflammatory status in chronic obstructive pulmonary disease patients with pulmonary Pseudomonas aeruginosa colonization. (PMID:31106488)
• Lipopolysaccharide-Binding Protein and Bactericidal/Permeability-Increasing Protein in Lipid Metabolism and Cardiovascular Diseases. (PMID:32705592)
• BPI overexpression suppresses Treg differentiation and induces exosome-mediated inflammation in systemic lupus erythematosus. (PMID:34815797)
• Molecular Evolution of the Bactericidal/Permeability-Increasing Protein (BPIFA1) Regulating the Innate Immune Responses in Mammals. (PMID:36672756)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpi	ENSMUSG00000052922
rattus_norvegicus	Bpi	ENSRNOG00000034195

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191), BPIFA1 (ENSG00000198183)

Protein

Protein identifiers

Bactericidal permeability-increasing protein — P17213 (reviewed: P17213)

Alternative names: CAP 57

All UniProt accessions (4): P17213, A0A0D9SFX6, A0A2R8YDF1, H0Y738

UniProt curated annotations — full annotation on UniProt →

Function. The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa.

Subunit / interactions. Monomer. Homodimer; disulfide-linked.

Subcellular location. Secreted. Cytoplasmic granule membrane.

Tissue specificity. Restricted to cells of the myeloid series.

Domain organisation. The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested. The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues.

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

RefSeq proteins (1): NP_001716* (*=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 (73 total): strand 28, helix 12, sequence variant 11, region of interest 6, sequence conflict 6, mutagenesis site 4, turn 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1EWF	X-RAY DIFFRACTION	1.7
1BP1	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17213-F1	92.70	0.89

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): 166–206

Glycosylation sites (1): 380

Mutagenesis-validated functional residues (4):

Position	Phenotype
49	no impairment of secretion and increased propensity for dimer formation.
163	no impairment of secretion and/or biological activity. loss of dimer formation.
166	poorly secreted. loss of lps-binding and biological activity.
206	not secreted.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-6798695	Neutrophil degranulation
R-HSA-6803157	Antimicrobial peptides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades

MSigDB gene sets: 135 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_64, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_6_PRODUCTION, MODULE_75, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (9): lipopolysaccharide-mediated signaling pathway (GO:0031663), negative regulation of interleukin-6 production (GO:0032715), negative regulation of interleukin-8 production (GO:0032717), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of macrophage activation (GO:0043031), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), immune system process (GO:0002376), defense response to bacterium (GO:0042742)

GO Molecular Function (2): lipopolysaccharide binding (GO:0001530), lipid binding (GO:0008289)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), azurophil granule lumen (GO:0035578), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	3
Toll-like Receptor Cascades	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of cytokine production	2
secretory granule lumen	2
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
negative regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
immune response	1
defense response to symbiont	1
defense response to bacterium	1
biological_process	1
defense response	1
response to bacterium	1
lipid binding	1
carbohydrate derivative binding	1
binding	1
vacuolar lumen	1
azurophil granule	1
specific granule	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPI	MPO	P05164	982
BPI	LTF	P02788	933
BPI	CTSG	P08311	917
BPI	ELANE	P08246	897
BPI	AZU1	P20160	794
BPI	AMY1B	P04745	786
BPI	AMY2A	P04746	763
BPI	PRTN3	P15637	757
BPI	BPIFA1	Q9NP55	720
BPI	CAMP	P49913	716
BPI	AMY2B	P19961	666
BPI	BPIFA2	Q96DR5	609
BPI	ALB	P02768	531
BPI	STATH	P02808	490
BPI	BPIFB1	Q8TDL5	479

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SLAMF9	BPI	psi-mi:“MI:0915”(physical association)	0.400
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
CD2BP2	PRPF4	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
ELOA2	XRCC2	psi-mi:“MI:0914”(association)	0.350
EGFL8	IGLC7	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Affinity Capture-MS), BPI (Co-fractionation)

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, P17454, Q67E05, Q6AXU0, P55065

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IRX1	“down-regulates quantity by repression”	BPI	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	8
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

1706 predictions. Top by Δscore:

Variant	Effect	Δscore
20:38304352:CGGTA:C	donor_loss	1.0000
20:38304353:GGT:G	donor_loss	1.0000
20:38304354:G:GA	donor_loss	1.0000
20:38304354:G:GG	donor_gain	1.0000
20:38304355:T:C	donor_loss	1.0000
20:38307565:A:AG	acceptor_gain	1.0000
20:38307566:G:GG	acceptor_gain	1.0000
20:38307566:GCC:G	acceptor_gain	1.0000
20:38308928:AGCAT:A	acceptor_gain	1.0000
20:38308929:GC:G	acceptor_gain	1.0000
20:38308929:GCATG:G	acceptor_gain	1.0000
20:38309038:G:GT	donor_gain	1.0000
20:38309038:G:T	donor_gain	1.0000
20:38309039:A:T	donor_gain	1.0000
20:38309054:TTCTT:T	donor_gain	1.0000
20:38309059:G:GG	donor_gain	1.0000
20:38310490:GAA:G	acceptor_gain	1.0000
20:38310490:GAAAA:G	acceptor_gain	1.0000
20:38310648:GTGGG:G	donor_gain	1.0000
20:38320178:TCTA:T	acceptor_loss	1.0000
20:38320179:CTA:C	acceptor_loss	1.0000
20:38320180:TAGT:T	acceptor_loss	1.0000
20:38320181:A:AG	acceptor_gain	1.0000
20:38320181:A:C	acceptor_loss	1.0000
20:38320182:G:A	acceptor_loss	1.0000
20:38320182:G:GT	acceptor_gain	1.0000
20:38320182:GT:G	acceptor_gain	1.0000
20:38320182:GTA:G	acceptor_gain	1.0000
20:38320182:GTAA:G	acceptor_gain	1.0000
20:38320182:GTAAT:G	acceptor_gain	1.0000

AlphaMissense

3200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:38323870:G:A	G257R	0.977
20:38323870:G:C	G257R	0.977
20:38323991:C:A	A297D	0.977
20:38309036:T:A	W122R	0.976
20:38309036:T:C	W122R	0.976
20:38326277:T:C	F340L	0.967
20:38326279:T:A	F340L	0.967
20:38326279:T:G	F340L	0.967
20:38323953:G:A	M284I	0.966
20:38323953:G:C	M284I	0.966
20:38323953:G:T	M284I	0.966
20:38323870:G:T	G257W	0.965
20:38310547:T:C	L148P	0.961
20:38309030:G:T	G120W	0.956
20:38337149:T:C	F477L	0.956
20:38337151:C:A	F477L	0.956
20:38337151:C:G	F477L	0.956
20:38323876:T:C	F259L	0.955
20:38323878:T:A	F259L	0.955
20:38323878:T:G	F259L	0.955
20:38326418:T:C	F387L	0.954
20:38326420:C:A	F387L	0.954
20:38326420:C:G	F387L	0.954
20:38307567:C:A	A48D	0.953
20:38323871:G:A	G257E	0.953
20:38335612:G:C	G455R	0.950
20:38309031:G:A	G120E	0.949
20:38310514:T:C	L137P	0.949
20:38326419:T:C	F387S	0.949
20:38304330:T:C	I40T	0.948

dbSNP variants (sampled 300 via entrez): RS1000011104 (20:38309451 T>C), RS1000046071 (20:38336442 C>T), RS1000053022 (20:38333438 G>A,T), RS1000096626 (20:38330873 A>G), RS1000229832 (20:38312873 T>C,G), RS1000426106 (20:38323506 A>G), RS1000534363 (20:38308188 G>C), RS1000553073 (20:38329688 G>A), RS1000678026 (20:38320886 G>A,C), RS1000699312 (20:38324199 A>G), RS1000860454 (20:38318655 G>A,T), RS1000910947 (20:38303238 C>A), RS1000918767 (20:38312779 G>A), RS1001283426 (20:38306439 T>C), RS1001320462 (20:38336146 G>A,C,T)

Disease associations

OMIM: gene MIM:109195 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005351_9	Carboplatin disposition in epthelial ovarian cancer	9.000000e-06
GCST90002379_161	Basophil count	2.000000e-10
GCST90002393_430	Monocyte count	1.000000e-10
GCST90002394_575	Monocyte percentage of white cells	1.000000e-10
GCST90002394_576	Monocyte percentage of white cells	7.000000e-15
GCST90002407_645	White blood cell count	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cadmium sulfate	increases expression	2
Arsenic Trioxide	increases expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
Tretinoin	increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
aflatoxin B2	decreases methylation	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cyclophosphamide	decreases expression	1
Diazinon	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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