DEFA1

Summary

DEFA1 (defensin alpha 1, HGNC:2761) is a protein-coding gene on chromosome 8p23.1, encoding Neutrophil defensin 1 (P59665). Effector molecule of the innate immune system that acts via antibiotic-like properties against a broad array of infectious agents including bacteria, fungi, and viruses or by promoting the activation and maturation of some APCs. In precision oncology, DEFA1 EXPRESSION confers sensitivity to Docetaxel in Prostate Cancer (CIViC Level B).

Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. The protein encoded by this gene, defensin, alpha 1, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. Several alpha defensin genes are clustered on chromosome 8. This gene differs from defensin, alpha 3 by only one amino acid. This gene and the gene encoding defensin, alpha 3 are both subject to copy number variation.

Source: NCBI Gene 1667 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 4 total
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_004084

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2761
Approved symbol	DEFA1
Name	defensin alpha 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	HNP-1
Ensembl gene	ENSG00000206047
Ensembl biotype	protein_coding
OMIM	125220
Entrez	1667

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000382692, ENST00000873418, ENST00000946643

RefSeq mRNA: 1 — MANE Select: NM_004084 NM_004084

CCDS: CCDS34797

Canonical transcript exons

ENST00000382692 — 3 exons

Exon	Start	End
ENSE00001493017	6980013	6980092
ENSE00001645348	6978460	6978646
ENSE00001733924	6977649	6977879

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 98.58.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	98.58	gold quality
granulocyte	CL:0000094	98.52	gold quality
monocyte	CL:0000576	97.57	gold quality
leukocyte	CL:0000738	97.56	gold quality
blood	UBERON:0000178	97.38	gold quality
bone marrow	UBERON:0002371	93.70	gold quality
spleen	UBERON:0002106	91.63	gold quality
bone marrow cell	CL:0002092	87.67	gold quality
upper lobe of left lung	UBERON:0008952	84.41	gold quality
descending thoracic aorta	UBERON:0002345	81.73	gold quality
placenta	UBERON:0001987	80.60	gold quality
lung	UBERON:0002048	80.03	gold quality
right coronary artery	UBERON:0001625	77.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.88	gold quality
right lobe of liver	UBERON:0001114	74.74	gold quality
apex of heart	UBERON:0002098	73.47	gold quality
liver	UBERON:0002107	72.49	gold quality
heart left ventricle	UBERON:0002084	72.48	gold quality
lymph node	UBERON:0000029	72.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.92	gold quality
right lobe of thyroid gland	UBERON:0001119	70.81	gold quality
substantia nigra	UBERON:0002038	70.59	gold quality
gastrocnemius	UBERON:0001388	70.54	gold quality
amygdala	UBERON:0001876	70.51	gold quality
temporal lobe	UBERON:0001871	69.87	gold quality
caudate nucleus	UBERON:0001873	69.41	gold quality
left lobe of thyroid gland	UBERON:0001120	69.39	gold quality
heart	UBERON:0000948	69.27	gold quality
gall bladder	UBERON:0002110	69.01	gold quality
right atrium auricular region	UBERON:0006631	68.33	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	233876.11
E-MTAB-7407	yes	56160.16
E-GEOD-150728	yes	24364.77
E-CURD-122	yes	13838.69
E-CURD-112	yes	6911.51
E-CURD-126	yes	4487.50
E-MTAB-8495	yes	3242.80
E-HCAD-8	yes	2905.06
E-CURD-98	yes	2811.51
E-HCAD-29	yes	2744.68
E-HCAD-1	yes	2411.81
E-GEOD-139324	yes	2116.42
E-CURD-79	yes	1770.04
E-HCAD-4	yes	1543.89
E-CURD-55	yes	201.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting DEFA1, 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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-4433A-3P	97.75	62.82	1435

Literature-anchored findings (GeneRIF, showing 40)

• ADP ribosylation 1 regulates its biological properties (PMID:12060767)
• increased levels in fetal disease, premature rupture of membranes, and preterm labor (PMID:12710851)
• results suggest that alpha-defensin-1 inhibits HIV-1 infection following viral entry but that alpha-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF. (PMID:12767998)
• Characterization of the molecular basis for the recognition between the 45-residue pro-peptide and the C-terminal functional domain of HNP-1. (PMID:12823617)
• These results indicate that neutrophil defensins HNP-1, -2, and -3 increase epithelial wound repair in vitro, which involves migration and proliferation, mucin production, epidermal growth factor receptor activation and downstream signaling pathways. (PMID:12871849)
• BPI and HNP1-3 are accumulated in the synovial cavity of patients with rheumatoid arthritis (PMID:12913926)
• HNP-1 is a potentially important regulator of neovascularizaiton, suggesting a new link between inflammation and angiogenesis. (PMID:15208269)
• Data demonstrate that, in the absence of serum, alpha-defensin-1 may act directly on the virus, but, in the presence of serum, its effects are on the cell, where it inhibits HIV-1 replication. (PMID:15719067)
• HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in anthrax-lethal-toxin-treated macrophages. (PMID:15772169)
• expression levels in human white blood cells showed clear correlation between relative proportions of DEFA1:DEFA3 mRNA and corresponding gene numbers. However, there was no relationship between total (DEFA1+DEFA3) mRNA levels and total gene copy number (PMID:15944200)
• the Arg5-Glu13 salt bridge in alpha-defensin is conserved for defensin in vivo stability (PMID:16246847)
• Subjects were genotyped for alpha-defensin-1/alpha-defensin-3, and four beta-defensin-1 polymorphisms. These polymorphisms may not be important in abnormally rapid lung function decline or susceptibility to lower respiratory infections. (PMID:16700921)
• The myeloid def1 promoter contains a weak TATA box plus one requisite and one helper site that specifically recruit GA-binding protein (def1-binding protein) and PU.1 into an active transcription site. (PMID:16709851)
• HNP1 (human neutrophil protein 1) inhibited diphtheria toxin (DT)- or Pseudomonas exotoxin A (ETA)-mediated ADP-ribosylation of eEF2 (eukaryotic elongation factor 2) and protected HeLa cells against DT- or ETA-induced cell death. (PMID:16817779)
• data suggest that alpha-defensins within lymphoid tissue are expressed by granulocytes and are prevalent in HIV-1-seronegative individuals with inflammatory processes as well as HIV-1-infected individuals (PMID:16837860)
• HNP-1 interacts with both C1q and MBL efficiently resulting in inhibition of both the classical and the lectin pathway of complement. (PMID:17448537)
• Alpha-defensins 1-3 levels are nonspecifically elevated in stools from patients with colorectal neoplasia and likely originate from white blood cells. Alpha-defensins 1-3 in stool might serve as markers of inflammatory bowel conditions. (PMID:17531545)
• HNP-1 controls afferent discharge and modulates effects of glutamine in vestibular end organs of frog. (PMID:17606342)
• human defensin alpha-1 causes membrane pore formation in a human parasite, leading to trypanosome destruction. (PMID:17635867)
• Human alpha-defensin-1 inhibited influenza virus replication and viral protein synthesis. (PMID:17703413)
• Serum alpha-defensin (-1, -2 and -3) concentrations are increased in type 1 diabetic patients with diabetic nephropathy. (PMID:18003664)
• We have found that the alpha-defensins HNP1 and HD5 have potent antiadenoviral activity. These molecules block HAdV infection by stabilizing the virus capsid, thereby preventing uncoating and virus-mediated endosome penetration. (PMID:18191790)
• These results support the hypothesis that HNPs can suppress hepatic glucose production through an intracellular mechanism distinct from the classical insulin signaling pathway. (PMID:18347011)
• Clostridium difficile toxin B interacts with high affinity with HNP-1 which may provide a defense mechanism against clostridial glucosylating cytotoxins. (PMID:18435932)
• There are increased levels of human neutrophil alpha-defensins (alpha-defensin-1, -2, and -3) in chronic venous leg ulcers. (PMID:18472248)
• The authors analyzed the sensitivities of different pneumococcal strains to HNP1-3 and found that encapsulated strains are efficiently killed at physiological concentrations (7.5 microg/ml). (PMID:18474654)
• results indicate that intracellularly expressed HNP1 induces tumor cell apoptosis, which inhibits tumor growth (PMID:18566229)
• hydrophobic forces have a dominant role in mediating the interactions between HNP1 and its propeptide–a finding largely contrasting the commonly held view that the interactions are of an electrostatic nature. (PMID:18616948)
• In African Americans, midpregnancy human neutrophil peptide 1-3 levels were more informative to preterm delivery risk than was bacterial vaginosis (PMID:18757648)
• alpha-defensin human neutrophil protein 1 (HNP1) and human alpha-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral lifecycle. (PMID:18782756)
• Upregulation of HNP1 is associated with colorectal adenomas and carcinomas. (PMID:18957723)
• Salivary HNP1, HNP-2 concentrations increased following exercise (PMID:19263072)
• HNP-1 and HBD-1 promoted the up-regulation of CD91 on the DC surface (PMID:19477909)
• HNP1 and HD5 kill E. coli by a process that is mechanistically distinct from their actions that kill S. aureus; and chiral molecular recognition is not a stringent prerequisite for other functions of the defensins (PMID:19640840)
• HNP1 mediates host immune responses to tumors in situ through the recruitment and subsequent activation of immature dendritic cells (PMID:19861439)
• A population of immature dysplastic granulocytes contributes to the chronic myelomonocytic leukemia phenotype through production of alpha-defensins HNP1-3 that suppress the differentiation capabilities of monocytes. (PMID:19864642)
• Data show that ADP-ribosylation of HNP-1 in vitro generated a product with ADP-ribose on arginine 24, and ornithine replacing arginine at position 14. (PMID:19897717)
• Combining the distance constraints from the 3d experiment and the chemical-shift-derived torsion angles, we obtained a de novo high-resolution NMR structure of HNP-1 (PMID:19963419)
• The solid-state NMR structure of HNP-1 has close similarity to the crystal structures of the HNP family, with the exception of the loop region between the first and second beta-strands. (PMID:20097206)
• The total amount of gingival crevicular fluid human neutrophil peptides 1 and 2 were not different among periodontitis, gingivitis, and health control groups; there was no correlation with clinical periodontal parameters. (PMID:20151808)

Cross-species orthologs

40 orthologs

Organism	Symbol	Gene ID
mus_musculus	Defa39	ENSMUSG00000058618
mus_musculus	Defa26	ENSMUSG00000060070
mus_musculus	Defa17	ENSMUSG00000060208
mus_musculus	Defa35	ENSMUSG00000061845
mus_musculus	Defa38	ENSMUSG00000061958
mus_musculus	Defa34	ENSMUSG00000063206
mus_musculus	Defa24	ENSMUSG00000064213
mus_musculus	Defa37	ENSMUSG00000065956
mus_musculus	Defa28	ENSMUSG00000074434
mus_musculus	Defa29	ENSMUSG00000074437
mus_musculus	Defa5	ENSMUSG00000074439
mus_musculus	Defa3	ENSMUSG00000074440
mus_musculus	Defa40	ENSMUSG00000074441
mus_musculus	Defa31	ENSMUSG00000074442
mus_musculus	Defa22	ENSMUSG00000074443
mus_musculus	Defa30	ENSMUSG00000074444
mus_musculus	Defa23	ENSMUSG00000074446
mus_musculus	Defa21	ENSMUSG00000074447
mus_musculus	Defa43	ENSMUSG00000079113
mus_musculus	Defa42	ENSMUSG00000079114
mus_musculus	Defa41	ENSMUSG00000079116
mus_musculus	AY761185	ENSMUSG00000079120
mus_musculus	Defa33	ENSMUSG00000094362
mus_musculus	Defa36	ENSMUSG00000094662
mus_musculus	Defa25	ENSMUSG00000094687
mus_musculus	Defa32	ENSMUSG00000094818
mus_musculus	Defa20	ENSMUSG00000095066
mus_musculus	Defa2	ENSMUSG00000096295
rattus_norvegicus	Np4	ENSRNOG00000028707
rattus_norvegicus	Defal1	ENSRNOG00000029462
rattus_norvegicus	Defa5	ENSRNOG00000030093
rattus_norvegicus	Defa24	ENSRNOG00000030524
rattus_norvegicus	Defa3	ENSRNOG00000038133
rattus_norvegicus	RatNP-3b	ENSRNOG00000038135
rattus_norvegicus	Defa31	ENSRNOG00000061751
rattus_norvegicus	Defa9	ENSRNOG00000068468
rattus_norvegicus	Np4	ENSRNOG00000069755
rattus_norvegicus		ENSRNOG00000078458
rattus_norvegicus	Defa8	ENSRNOG00000081022
rattus_norvegicus	Defa9	ENSRNOG00000091367

Paralogs (5): DEFA5 (ENSG00000164816), DEFA4 (ENSG00000164821), DEFA6 (ENSG00000164822), DEFA3 (ENSG00000239839), DEFA1B (ENSG00000240247)

Protein

Protein identifiers

Neutrophil defensin 1 — P59665 (reviewed: P59665)

Alternative names: Defensin, alpha 1, HNP-1

All UniProt accessions (1): P59665

UniProt curated annotations — full annotation on UniProt →

Function. Effector molecule of the innate immune system that acts via antibiotic-like properties against a broad array of infectious agents including bacteria, fungi, and viruses or by promoting the activation and maturation of some APCs. Interacts with the essential precursor of cell wall synthesis lipid II to inhibit bacterial cell wall synthesis. Inhibits adenovirus infection via inhibition of viral disassembly at the vertex region, thereby restricting the release of internal capsid protein pVI, which is required for endosomal membrane penetration during cell entry. In addition, interaction with adenovirus capsid leads to the redirection of viral particles to TLR4 thereby promoting a NLRP3-mediated inflammasome response and interleukin 1-beta (IL-1beta) release. Induces the production of proinflammatory cytokines including type I interferon (IFN) in plasmacytoid dendritic cells (pDCs) by triggering the degradation of NFKBIA and nuclear translocation of IRF1, both of which are required for activation of pDCs.

Subunit / interactions. Tetramer. Dimer. Interacts with RETN. (Microbial infection) Interacts with HIV-1 surface protein gp120. (Microbial infection) Interacts with herpes virus 1 (HHV1) envelope glycoprotein B; this interaction inhibits viral infection.

Subcellular location. Secreted.

Post-translational modifications. ADP-ribosylation drastically reduces cytotoxic and antibacterial activities, and enhances IL8 production. Phosphorylation at Tyr-85 has been found in some cancer cell lines, and interferes with ADP-ribosylation.

Similarity. Belongs to the alpha-defensin family.

RefSeq proteins (1): NP_004075* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002366	Alpha-defensin_N	Domain
IPR006080	Beta/alpha-defensin_C	Domain
IPR006081	Alpha-defensin_C	Domain
IPR016327	Alpha-defensin	Family

Pfam: PF00323, PF00879

UniProt features (15 total): disulfide bond 3, strand 3, modified residue 3, peptide 2, signal peptide 1, propeptide 1, mutagenesis site 1, chain 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
9FQB	X-RAY DIFFRACTION	1.09
3HJ2	X-RAY DIFFRACTION	1.4
3GNY	X-RAY DIFFRACTION	1.56
3LO2	X-RAY DIFFRACTION	1.56
3LO6	X-RAY DIFFRACTION	1.56
3LO9	X-RAY DIFFRACTION	1.56
3LOE	X-RAY DIFFRACTION	1.56
2PM1	X-RAY DIFFRACTION	1.6
3LO1	X-RAY DIFFRACTION	1.6
3H6C	X-RAY DIFFRACTION	1.63
3LVX	X-RAY DIFFRACTION	1.63
3HJD	X-RAY DIFFRACTION	1.65
4LBF	X-RAY DIFFRACTION	1.7
4LBB	X-RAY DIFFRACTION	1.72
3LO4	X-RAY DIFFRACTION	1.75
4DU0	X-RAY DIFFRACTION	1.9
4LB7	X-RAY DIFFRACTION	1.9
4LB1	X-RAY DIFFRACTION	2
2KHT	SOLID-STATE NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59665-F1	73.61	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 78, 85, 88

Disulfide bonds (3): 73–93, 66–94, 68–83

Mutagenesis-validated functional residues (1):

Position	Phenotype
90	almost complete loss of bactericidal activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1461973	Defensins
R-HSA-1462054	Alpha-defensins
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 105 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GOBP_CELL_CHEMOTAXIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, MATTIOLI_MGUS_VS_PCL, CHEOK_RESPONSE_TO_HD_MTX_UP, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_CHEMOTAXIS, BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (18): innate immune response in mucosa (GO:0002227), chemotaxis (GO:0006935), immune response (GO:0006955), T cell chemotaxis (GO:0010818), antibacterial humoral response (GO:0019731), estrogen receptor signaling pathway (GO:0030520), killing of cells of another organism (GO:0031640), defense response to protozoan (GO:0042832), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), defense response to fungus (GO:0050832), defense response to virus (GO:0051607), disruption of plasma membrane integrity in another organism (GO:0051673), obsolete killing by host of symbiont cells (GO:0051873), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response (GO:0006952), defense response to bacterium (GO:0042742)

GO Molecular Function (2): pore-forming activity (GO:0140911), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Antimicrobial peptides	1
Defensins	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	3
defense response	3
antimicrobial humoral response	2
mucosal immune response	1
innate immune response	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
lymphocyte chemotaxis	1
T cell migration	1
nuclear receptor-mediated steroid hormone signaling pathway	1
cell killing	1
disruption of cell in another organism	1
response to protozoan	1
defense response to other organism	1
immune response	1
defense response to symbiont	1
response to fungus	1
response to virus	1
disruption of cellular anatomical structure in another organism	1
response to stress	1
response to bacterium	1
molecular_function	1
binding	1
cellular anatomical structure	1
Golgi apparatus	1
intracellular organelle lumen	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

28 interactions, top by confidence:

A	B	Type	Score
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
DEFA1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
FBXO4	AMD1	psi-mi:“MI:0914”(association)	0.530
Dynll1		psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
ZNF16	DEFA1	psi-mi:“MI:0915”(physical association)	0.370
DEFA1	GSK3B	psi-mi:“MI:0915”(physical association)	0.370
PLB1	WDR47	psi-mi:“MI:0914”(association)	0.350
rep		psi-mi:“MI:0914”(association)	0.350
IRAK2	LTF	psi-mi:“MI:0914”(association)	0.350
ROCK2	CLTB	psi-mi:“MI:0914”(association)	0.350
TEX14	DNAJB6	psi-mi:“MI:0914”(association)	0.350
SRPK1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
ERO1A	LTF	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
ITGA5	ORC4	psi-mi:“MI:0914”(association)	0.350
P/V/C	KPNA3	psi-mi:“MI:0914”(association)	0.350
MYB	A2ML1	psi-mi:“MI:0914”(association)	0.350
DEFA1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
PFDN1	DEFA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (173): DEFA1 (Affinity Capture-MS), DEFA1B (Affinity Capture-MS), IGFBP2 (Affinity Capture-MS), PPP3CC (Affinity Capture-MS), DAK (Affinity Capture-MS), CTBS (Affinity Capture-MS), PPP3R1 (Affinity Capture-MS), LIFR (Affinity Capture-MS), SUSD1 (Affinity Capture-MS), CTSF (Affinity Capture-MS), PPP3CA (Affinity Capture-MS), ARSB (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), PXDN (Affinity Capture-MS), TMEM2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2I6EDM5, A0A3G3C7S6, A1Z0M0, A6YB85, B2KJ30, D2Y2M4, D2Y2N3, D6C4K9, D6C4L2, P0CB11, P0DUJ6, P18512, P18513, P28312, P50705, P50708, P50714, P56714, P59665, P59666, P60030, P60031, P60032, P61516, P69751, P69754, P82106, P82951, Q01524, Q3L180, Q4JEI2, Q5G860, Q5G863, Q5G864, Q7T273, Q801Y3, Q80T19, Q99MH3, Q9BP89, Q9BP99

Diamond homologs: A6YB85, B6ULW4, B6ULW5, B6ULW7, P01376, P01377, P07466, P07467, P07469, P0C8A2, P11477, P11478, P12838, P28309, P28310, P28311, P28312, P49112, P50704, P50705, P50707, P50708, P50709, P50711, P50712, P50713, P50714, P59665, P59666, P60030, P60031, P60032, P81465, P81467, P82270, P82271, P82319, P82320, Q01523, Q01524

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

101 predictions. Top by Δscore:

Variant	Effect	Δscore
8:6978455:CTCA:C	donor_loss	1.0000
8:6978456:TCA:T	donor_loss	1.0000
8:6978457:CAC:C	donor_loss	1.0000
8:6978458:ACCT:A	donor_loss	1.0000
8:6978510:T:TA	donor_gain	0.9900
8:6977886:C:CT	acceptor_gain	0.9800
8:6978449:G:A	donor_gain	0.9800
8:6978503:A:AT	donor_gain	0.9800
8:6978505:C:CT	donor_gain	0.9800
8:6977887:A:T	acceptor_gain	0.9700
8:6978458:A:AC	donor_gain	0.9700
8:6978459:C:CC	donor_gain	0.9700
8:6977880:C:CC	acceptor_gain	0.9600
8:6977895:C:CT	acceptor_gain	0.9600
8:6977896:A:C	acceptor_gain	0.9600
8:6977878:GCC:G	acceptor_loss	0.9500
8:6977881:T:A	acceptor_loss	0.9500
8:6977878:GC:G	acceptor_gain	0.9400
8:6977878:GCCT:G	acceptor_gain	0.9400
8:6977879:CC:C	acceptor_gain	0.9400
8:6977877:AGCC:A	acceptor_gain	0.9300
8:6977879:CCTG:C	acceptor_gain	0.9200
8:6978564:G:A	donor_gain	0.9200
8:6977876:GAGCC:G	acceptor_gain	0.9100
8:6977877:AGC:A	acceptor_gain	0.9100
8:6977880:C:T	acceptor_gain	0.9100
8:6977875:TGAGC:T	acceptor_gain	0.8900
8:6978459:CCTGG:C	donor_gain	0.8900
8:6977876:GAGC:G	acceptor_gain	0.8800
8:6977880:C:G	acceptor_gain	0.8800

AlphaMissense

598 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000450787 (8:6979988 A>G), RS1000742250 (8:6981886 C>G,T), RS1009966938 (8:6979735 T>G), RS1020397770 (8:6979765 G>C), RS1024332274 (8:6980357 G>A), RS1034976112 (8:6980151 G>A), RS1041487159 (8:6981831 C>G), RS1051454839 (8:6979613 A>G), RS1051849879 (8:6981772 G>A), RS111758096 (8:6977324 G>T), RS112771638 (8:6977323 G>T), RS113515472 (8:6978295 C>T), RS1156978650 (8:6980948 C>T), RS1157445227 (8:6980873 C>A,T), RS1157757670 (8:6979920 C>T)

Disease associations

OMIM: gene MIM:125220 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002136_14	Periodontitis (PAL4Q3)	6.000000e-06
GCST002136_5	Periodontitis (PAL4Q3)	7.000000e-06
GCST002929_16	Chromium levels	1.000000e-06
GCST004368_5	Endometriosis	1.000000e-06
GCST006585_102	Blood protein levels	3.000000e-12
GCST009269_9	Dental caries (decayed and filled deciduous teeth)	5.000000e-06
GCST90002380_52	Basophil percentage of white cells	4.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3885531 (PROTEIN-PROTEIN INTERACTION)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
DEFA1 EXPRESSION	Docetaxel	Prostate Cancer	Sensitivity/Response	CIViC B	EID808

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression	2
Tretinoin	increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases activity, increases phosphorylation, decreases phosphorylation, decreases reaction	1
SB 203580	decreases reaction, increases activity, increases phosphorylation, decreases phosphorylation	1
Irinotecan	decreases expression	1
Progesterone	increases expression	1
Quercetin	decreases phosphorylation, decreases reaction, increases activity, increases expression, increases secretion	1
Valproic Acid	increases methylation	1
Mifepristone	decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3820562	Binding	Inhibition of CCL5 (unknown origin)-HNP1 (unknown origin) interaction in HUVEC assessed as reduction in CCL5-HNP1-driven human monocyte adhesion at 100 ug/ml pre-incubated for 5 mins before human monocyte addition	Structure-Based Design of Peptidic Inhibitors of the Interaction between CC Chemokine Ligand 5 (CCL5) and Human Neutrophil Peptides 1 (HNP1). — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 cancer cell line, 2 factor-dependent cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C6XB	32D/HNP	Factor-dependent cell line	Male
CVCL_C6XC	32Dcl3/HNP	Factor-dependent cell line	Male
CVCL_C6XD	AtT-20/HNP	Cancer cell line	Sex unspecified
CVCL_C6XE	J774.1/HNP	Cancer cell line	Female
CVCL_C6XF	NIH 3T3/HNP	Spontaneously immortalized cell line	Male
CVCL_C6XG	RAW264.7/HNP	Cancer cell line	Male

Clinical trials (associated diseases)

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