DEFA5

Summary

DEFA5 (defensin alpha 5, HGNC:2764) is a protein-coding gene on chromosome 8p23.1, encoding Defensin alpha 5 (Q01523). Host-defense peptide that maintains sterility in the urogenital system.

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. Several of the alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 5, is highly expressed in the secretory granules of Paneth cells of the ileum.

Source: NCBI Gene 1670 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 43 total — 1 pathogenic
• MANE Select transcript: NM_021010

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2764
Approved symbol	DEFA5
Name	defensin alpha 5
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	HD-5
Ensembl gene	ENSG00000164816
Ensembl biotype	protein_coding
OMIM	600472
Entrez	1670

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000330590

RefSeq mRNA: 1 — MANE Select: NM_021010 NM_021010

CCDS: CCDS5963

Canonical transcript exons

ENST00000330590 — 2 exons

Exon	Start	End
ENSE00001087773	7056526	7056739
ENSE00001314734	7055304	7055543

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 99.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 19.4229 / max 12261.5345, expressed in 23 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91726	19.4229	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	99.97	gold quality
small intestine	UBERON:0002108	98.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.01	gold quality
vermiform appendix	UBERON:0001154	68.15	gold quality
intestine	UBERON:0000160	63.05	gold quality
mucosa of stomach	UBERON:0001199	56.50	gold quality
right lung	UBERON:0002167	53.71	gold quality
transverse colon	UBERON:0001157	50.68	gold quality
colon	UBERON:0001155	50.37	gold quality
lymph node	UBERON:0000029	48.00	gold quality
rectum	UBERON:0001052	47.94	gold quality
blood	UBERON:0000178	46.14	gold quality
descending thoracic aorta	UBERON:0002345	45.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	44.65	gold quality
body of pancreas	UBERON:0001150	43.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	43.29	gold quality
body of stomach	UBERON:0001161	43.28	gold quality
Ammon’s horn	UBERON:0001954	42.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	41.69	gold quality
stomach	UBERON:0000945	41.46	gold quality
adenohypophysis	UBERON:0002196	41.35	gold quality
right ovary	UBERON:0002118	41.33	gold quality
minor salivary gland	UBERON:0001830	41.21	gold quality
bone marrow	UBERON:0002371	41.18	gold quality
body of uterus	UBERON:0009853	41.09	gold quality
right frontal lobe	UBERON:0002810	40.79	gold quality
saliva-secreting gland	UBERON:0001044	40.13	gold quality
spleen	UBERON:0002106	40.13	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	76708.71
E-MTAB-9801	yes	4.78
E-ANND-3	yes	3.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, TCF4

miRNA regulators (miRDB)

14 targeting DEFA5, 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-9-5P	100.00	72.28	2361
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-203B-3P	97.82	66.27	979

Literature-anchored findings (GeneRIF, showing 40)

• By acting as a prodefensin convertase in human Paneth cells, trypsin is involved in the regulation of innate immunity in the small intestine. (PMID:12021776)
• Defensin 5 transgenic mice were resistant to oral challenge with virulent Salmonella typhimurium; support for a critical in vivo role of epithelial-derived defensins in mammalian host defence (PMID:12660734)
• DEFA5 displays antimicrobial activity against E. coli, E. aerogenes, B. cereus, and S. aureus. (PMID:15616305)
• Crystal structure of HD-5. (PMID:17088326)
• HD-5 binds to the cell membrane of intestinal epithelial cells and induces secretion of the chemokine interleukin (IL)-8 (PMID:17250830)
• 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)
• The persistence of HD5-chymotrypsinogen-trypsin complex in Crohn disease may be attributable to increased luminal levels of proteinase inhibitors such as alpha1-anti-trypsin. (PMID:18258845)
• Single nucleotide polymorphism in defensin alpha 5 Paneth cell associated with inflammatory bowel diseases in caucasoid population. (PMID:18394979)
• Clostridium difficile toxin B interacts with high affinity with HD5 which may provide a defense mechanism against clostridial glucosylating cytotoxins. (PMID:18435932)
• the primary function of the conserved salt bridge in HD5 is to ensure correct processing of proHD5 and subsequent stabilization of mature alpha-defensin in vivo (PMID:18499668)
• HBD-2 and HD-5 may be involved in defending against invasion by BV-related microorganisms and the decrease in IL-4 concentration may increase susceptibility to bacterial vaginosis (PMID:18635180)
• 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)
• The concentrations of human defensin 5, HBD1, and HBD2 in vulvovaginal candidiasis patients were higher than in controls. (PMID:19080508)
• Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. (PMID:19250512)
• Self-association and multivalent binding may play integral roles in the ability of alpha-defensin 5 (HD5) to protect against infections caused by viruses and other infectious agents. (PMID:19542459)
• Results report on the antibacterial properties and cellular interaction of Human Defensin 5 as a function of its positive charge and hydrophobicity. (PMID:19589339)
• 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)
• Data show that DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. (PMID:19855381)
• The authors provide direct evidence that human alpha-defensins block adenovirus infection by preventing uncoating during cell entry. (PMID:20130047)
• This study demonstrated the multifunctional roles of the activation process in human defensin-5. (PMID:20375624)
• HalphaD-5 and HbetaD-2 may protect fallopian tubes during microbial infection. (PMID:20629326)
• To respond to LPS stimulation, human primary endocervical epithelial cells may function in the mucosal immune defense through TLR4 activation and HD5 secretion. (PMID:20819643)
• Statistical analysis of gene expression showed a distinction between regions 1 and 2 of the small intestin for HD5. (PMID:21125297)
• Defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment. (PMID:21672195)
• The hydrophobicity of regions 2, 9 & 10 was higher than in other regions. It was difficult for the HD molecule to have many conformations because of its 3 S-S bridges; however, it responds to various external factors by restricting conformation. (PMID:21873175)
• Several arginine residues and tyrosine 27 are important for HD-5 antibacterial activity. (PMID:22354633)
• structural analysis of human enteric alpha-defensin HD5 shows a crucial role for hydrophobicity at the dimer interface (PMID:22573326)
• study demonstrate that binding of integrin alphavbeta5 and alpha defensin 5 have opposite effects on the elastic response of adenovirus type 35, revealing a direct link between virus-host interactions and the mechanical properties of the capsid (PMID:23269786)
• Subnanometer resolution cryo-electron microscopy structures of HD5 complexed with both neutralization-sensitive and -resistant human adenovirus chimeras, were determined. (PMID:23620768)
• This study considers the redox properties of HD-5 and reports that the reduced form, HD-5 red, is a zinc-ion chelator. (PMID:23841778)
• E-cadherin expression in squamous cells is reduced by HD-5 (PMID:23958301)
• Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum-deprived conditions is a consequence of defensin-mediated cytotoxicity. (PMID:24086683)
• human alpha defensin 5 increases LGR stem cell migration into wound beds, leading to enhanced healing, bacterial reduction, and hair production through the augmentation of key Wnt and wound healing transcripts. (PMID:24165598)
• HD5 neutralizes JC polyomavirus infection by stabilizing the viral capsid and disrupting virus trafficking. (PMID:24198413)
• Data indicate that cellular effects of defensin 5 involve interactions with the extra-cellular domain of tumor necrosis Factor 1. (PMID:24681099)
• our results highlight the potential contribution of altered alpha-defensin HD-5 expression in the formation of a viral/tumour-permissive environment in high-risk HPV infection and progression to cancer of the uterine cervix (PMID:25196670)
• The study reports the screening of human defensin 5 against the Keio Collection of E. coli strains and shows how this important hostdefense peptide kills bacteria and how bacteria protect themselves against the attack from the human host. (PMID:25430675)
• Authors show that although NOD2 by itself can slightly up-regulate expression of HD5 and HD6, it can strongly down-regulates their expression during differentiation of the Paneth cell lineage mainly by inhibiting activation of the MAPK pathway. (PMID:25433720)
• Enteric alpha-defensin HD5 and beta-defensin hBD2 shared similar toxin-unfolding effects with HNP1, albeit to different degrees. (PMID:25517613)
• These data support a model in which HD5 prevents furin from accessing human papillomavirus 16 L2 by occluding the furin cleavage site via direct binding to the viral capsid. (PMID:25540379)

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): DEFA4 (ENSG00000164821), DEFA6 (ENSG00000164822), DEFA1 (ENSG00000206047), DEFA3 (ENSG00000239839), DEFA1B (ENSG00000240247)

Protein

Protein identifiers

Defensin alpha 5 — Q01523 (reviewed: Q01523)

Alternative names: Defensin-5, HD5(20-94)

All UniProt accessions (1): Q01523

UniProt curated annotations — full annotation on UniProt →

Function. Host-defense peptide that maintains sterility in the urogenital system. Has antimicrobial activity against a wide range of bacteria, including Gram-negative E.coli, P.aeruginosa and S.typhimurium, and Gram-positive E.aerogenes, S.aureus, B.cereus, E.faecium and L.monocytogenes. Confers resistance to intestinal infection by S.typhimurium. Exhibits antimicrobial activity against enteric commensal bacteria such as B.adolescentis, L.acidophilus, B.breve, L.fermentum, B.longum and S.thermophilus. Binds to bacterial membranes and causes membrane disintegration. Induces the secretion of the chemokine IL-8 by intestinal epithelial cells. Binds to B.antracis lef/lethal factor, a major virulence factor from B.anthracis, and neutralizes its enzymatic activity. (Microbial infection) Acts as a target for S.flexneri infection by binding to the bacterium, possibly via bacterial surface proteins, and thereby augmenting infectivity via enhanced bacterial adhesion and invasion of epithelial cells and tissues.

Subunit / interactions. Homodimer. Homotetramer. Interacts with B.antracis lef/lethal factor.

Subcellular location. Secreted. Cytoplasmic vesicle. Secretory vesicle.

Tissue specificity. Expressed in the gastrointestinal, reproductive, and urinary tracts (at protein level). Expressed in Paneth cells of the small intestine (at protein level). Expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney (at protein level). Expressed in stratified squamous epithelial cells of the female genital tract epithelia, such as in vagina, ectocervix, endocervix, endometrium, and fallopian tube (at protein level). Endometrial expression correlates with stages of the menstrual cycle: Expression is low during the early proliferative phase, increased during the mid- to late proliferative phase, peaks during the early secretory phase of the cycle, and decreases during the mid- to late secretory phase.

Post-translational modifications. Glycosylated. Proteolytically cleaved at Arg-62 by trypsin. Both the propeptide form proHD5/HD5(20-94) and HD5(56-94) are cleaved into the lumenal peptide form HD5(63-94) by trypsin. Unprocessed proHD5 exerts antimicrobial activities, but peptide potency is enhanced by peptide processing. Proteolytically cleaved in duodenal fluid; derived fragments are antimicrobially active against commensal bacteria (in vitro). (Microbial infection) The disulfide bridges and homodimerization are a prerequisite for the enhancement of S.flexneri adhesion and invasion.

Induction. Up-regulated in fallopian tubes upon infection. Increased expression in kidneys with pyelonephritis.

Similarity. Belongs to the alpha-defensin family.

RefSeq proteins (1): NP_066290* (*=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 (33 total): mutagenesis site 20, peptide 5, strand 3, disulfide bond 3, signal peptide 1, sequence variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4RBX	X-RAY DIFFRACTION	1.1
4RBW	X-RAY DIFFRACTION	1.5
3I5W	X-RAY DIFFRACTION	1.63
1ZMP	X-RAY DIFFRACTION	1.65
4E82	X-RAY DIFFRACTION	1.7
5CUM	X-RAY DIFFRACTION	1.75
4E83	X-RAY DIFFRACTION	1.9
5CUJ	X-RAY DIFFRACTION	2.08
5CUI	X-RAY DIFFRACTION	2.4
4E86	X-RAY DIFFRACTION	2.75
2LXZ	SOLUTION NMR
2MIT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01523-F1	70.95	0.34

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 (3): 65–93, 67–82, 72–92

Mutagenesis-validated functional residues (20):

Position	Phenotype
67	prohibits tetramer formation; when associated with s-93.
69	enhanced antibacterial activity against both e.coli and s.aureus. enhanced membrane binding and membrane disintegration
71	reduced killing of s.aureus and e.coli. impairs antimicrobial activity against e.coli, e.aerogenes, s.aureus and b.cereu
71	impairs antimicrobial activity against s. aureus; when associated with k-90. reduced induction of il-8 secretion; when a
72	prohibits tetramer formation; when associated with s-92.
75	impairs antimicrobial activity against e.coli, e.aerogenes, s.aureus and b.cereus; when associated with a-94. reduced in
75	does not impair antimicrobial activity against e.coli, e.aerogenes, s.aureus and b.cereus; when associated with k-94. re
77	increased interaction with b.antracis lef/lethal factor.
83	enhanced antibacterial activity against both e.coli and s.aureus. disrupts homodimerization. enhanced membrane binding a
85	enhanced antibacterial activity against both e.coli and s.aureus.
86	enhanced antibacterial activity against both e.coli and s.aureus.
88	reduced interaction with b.antracis lef/lethal factor. reduced enhancement of s.flexneri infection.
89	disrupts homodimer-formation. reduced interaction with b.antracis lef/lethal factor and reduced killing of s.aureus. red
90	does not disrupt homodimer-formation. reduced enhancement of s.flexneri infection. impairs antimicrobial activity agains
90	impairs antimicrobial activity against s. aureus; when associated with k-71. reduced induction of il-8 secretion; when a
91	reduced interaction with b.antracis lef/lethal factor and decreased bactericidal activity against e.coli and s.aureus. r
92	prohibits tetramer formation; when associated with s-72.
93	prohibits tetramer formation; when associated with s-67.
94	impairs antimicrobial activity against e.coli, e.aerogenes, s.aureus and b.cereus; when associated with a-75. reduced in
94	does not impair antimicrobial activity against e.coli, e.aerogenes, s.aureus and b.cereus; when associated with k-75. re

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1461973	Defensins
R-HSA-1462054	Alpha-defensins
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)

MSigDB gene sets: 80 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MODULE_75, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CYTOKINE_PRODUCTION, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_SYMBIONT, GOBP_RESPONSE_TO_FUNGUS

GO Biological Process (15): antibacterial humoral response (GO:0019731), killing of cells of another organism (GO:0031640), positive regulation of interleukin-8 production (GO:0032757), 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), protein homotetramerization (GO:0051289), 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), positive regulation of membrane permeability (GO:1905710), immune system process (GO:0002376), defense response (GO:0006952), defense response to bacterium (GO:0042742)

GO Molecular Function (3): protein homodimerization activity (GO:0042803), pore-forming activity (GO:0140911), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), transport vesicle (GO:0030133), secretory granule (GO:0030141), midbody (GO:0030496), secretory granule lumen (GO:0034774), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Antimicrobial peptides	1
Defensins	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	3
antimicrobial humoral response	2
defense response	2
cellular anatomical structure	2
endomembrane system	2
cell killing	1
disruption of cell in another organism	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
immune response	1
defense response to symbiont	1
response to fungus	1
protein homooligomerization	1
protein tetramerization	1
disruption of cellular anatomical structure in another organism	1
regulation of membrane permeability	1
biological_process	1
response to stress	1
response to bacterium	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
cytoplasmic vesicle	1
secretory vesicle	1
secretory granule	1
cytoplasmic vesicle lumen	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFA5	ACE2	Q9BYF1	895
DEFA5	DEFB1	P60022	861
DEFA5	DEFB4A	O15263	820
DEFA5	REG3A	Q06141	695
DEFA5	CAMP	P49913	685
DEFA5	MMP7	P09237	670
DEFA5	DEFB103A	P81534	669
DEFA5	REG1B	P48304	619
DEFA5	MUC2	Q02817	606
DEFA5	REG1A	P05451	587
DEFA5	PLA2G2A	P14555	565
DEFA5	DEFB105A	Q8NG35	546
DEFA5	DEFB104A	Q8WTQ1	532
DEFA5	DEFB106A	Q8N104	527
DEFA5	DEFB107A	Q8IZN7	519

IntAct

12 interactions, top by confidence:

A	B	Type	Score
DEFA5	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
BCAR3	GAST	psi-mi:“MI:0914”(association)	0.530
DTX1	DEFA5	psi-mi:“MI:0915”(physical association)	0.370
DEFA5	PDE2A	psi-mi:“MI:0914”(association)	0.350
DEFA5	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (125): ARHGAP19 (Affinity Capture-MS), FAM35A (Affinity Capture-MS), WAPAL (Affinity Capture-MS), SUSD5 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), CILP2 (Affinity Capture-MS), GLCE (Affinity Capture-MS), IP6K1 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), CEP170B (Affinity Capture-MS), PC (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), KLHDC10 (Affinity Capture-MS), TMEM132A (Affinity Capture-MS)

ESM2 similar proteins: A6YB85, P01376, P01377, P07466, P07467, P07469, P0C8A1, P0C8A2, P0C8A4, P11477, P11478, P28309, P28310, P28311, P28312, P49112, P50704, P50705, P50707, P50708, P50709, P50711, P50712, P50713, P50714, P59665, P59666, P60030, P60031, P60032, P82106, P82319, P82320, Q01523, Q3L180, Q45VN2, Q5G859, Q5G861, Q5G863, Q5G864

Diamond homologs: A6YB85, B6ULW4, B6ULW5, B6ULW7, P01376, P01377, P07466, P07467, P07469, P0C8A2, P0C8A3, P11477, P12838, P28309, P28310, P28311, P28312, P50704, P50705, P50706, P50707, P50708, P50709, P50711, P50712, P50713, P50714, P50716, P60030, P60031, P60032, P82106, P82271, P82319, P82320, Q01523, Q01524, Q3L180, Q45VN2, Q4JEI2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815066	GRCh37/hg19 8p23.3-23.1(chr8:158048-9025197)x1	Pathogenic

SpliceAI

56 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7056554:T:TA	donor_gain	1.0000
8:7056589:C:A	donor_gain	1.0000
8:7055542:ACC:A	acceptor_loss	0.9900
8:7055544:C:CC	acceptor_gain	0.9900
8:7055544:C:G	acceptor_loss	0.9900
8:7056520:TCCTA:T	donor_loss	0.9900
8:7056521:CCTAC:C	donor_loss	0.9900
8:7056522:CTA:C	donor_loss	0.9900
8:7056523:TACCT:T	donor_loss	0.9900
8:7056524:A:AT	donor_loss	0.9900
8:7056525:CCTGA:C	donor_loss	0.9900
8:7056588:T:TA	donor_gain	0.9900
8:7055540:GAAC:G	acceptor_gain	0.9700
8:7055542:AC:A	acceptor_gain	0.9700
8:7055543:CC:C	acceptor_gain	0.9700
8:7056576:T:TA	donor_gain	0.9700
8:7056627:T:A	donor_gain	0.9700
8:7055541:AAC:A	acceptor_gain	0.9600
8:7055541:AACCT:A	acceptor_gain	0.9600
8:7055542:ACCTG:A	acceptor_gain	0.9600
8:7055543:CCTGT:C	acceptor_gain	0.9600
8:7055539:AGAAC:A	acceptor_gain	0.9500
8:7055544:CTGTG:C	acceptor_gain	0.9500
8:7055546:G:C	acceptor_gain	0.9500
8:7055546:G:GC	acceptor_gain	0.9500
8:7056434:A:C	donor_gain	0.9500
8:7055540:GAACC:G	acceptor_gain	0.9400
8:7055545:T:A	acceptor_gain	0.9300
8:7056641:AG:A	donor_gain	0.9100
8:7056433:A:AC	donor_gain	0.8900

AlphaMissense

588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7055471:C:G	C82S	0.936
8:7055472:A:T	C82S	0.936
8:7055516:C:G	C67S	0.935
8:7055517:A:T	C67S	0.935
8:7055501:C:G	C72S	0.926
8:7055502:A:T	C72S	0.926
8:7055513:C:G	R68P	0.922
8:7055441:C:G	C92S	0.920
8:7055442:A:T	C92S	0.920
8:7055471:C:T	C82Y	0.919
8:7055438:C:G	C93S	0.907
8:7055439:A:T	C93S	0.907
8:7055516:C:T	C67Y	0.907
8:7055522:C:G	C65S	0.900
8:7055523:A:T	C65S	0.900
8:7055515:G:C	C67W	0.899
8:7055522:C:T	C65Y	0.890
8:7055472:A:G	C82R	0.887
8:7055521:G:C	C65W	0.885
8:7055502:A:G	C72R	0.883
8:7055489:T:A	E76V	0.881
8:7055523:A:G	C65R	0.879
8:7055441:C:T	C92Y	0.878
8:7055438:C:T	C93Y	0.877
8:7055440:G:C	C92W	0.877
8:7055460:C:A	G86C	0.877
8:7055500:A:C	C72W	0.874
8:7055517:A:G	C67R	0.871
8:7055437:A:C	C93W	0.869
8:7055470:A:C	C82W	0.868

dbSNP variants (sampled 300 via entrez): RS1000136641 (8:7058723 T>G), RS1000578510 (8:7055786 A>G), RS1000617017 (8:7055692 A>T), RS1002027800 (8:7058648 G>A,C,T), RS1002196002 (8:7057770 C>T), RS1002222395 (8:7054909 G>A), RS1002252991 (8:7055156 A>G), RS1004835296 (8:7057921 G>T), RS1004888167 (8:7055199 A>G), RS1004961124 (8:7054959 A>G), RS1005025198 (8:7056246 C>G), RS1005550948 (8:7056011 CTCCTTTTTTT>C), RS1005586229 (8:7058155 A>C,G), RS1005802265 (8:7058410 A>G), RS1007261984 (8:7057369 G>A)

Disease associations

OMIM: gene MIM:600472 | 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
GCST002927_15	Mercury levels	4.000000e-07
GCST003078_2	Cerebrospinal fluid p-Tau181p:AB1-42 ratio	9.000000e-07
GCST006585_858	Blood protein levels	7.000000e-06
GCST90002379_113	Basophil count	7.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007709	p-tau:beta-amyloid 1-42 ratio measurement
EFO:0005090	basophil count

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
entinostat	decreases expression	1
clothianidin	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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