DEFB104A

Summary

DEFB104A (defensin beta 104A, HGNC:18115) is a protein-coding gene on chromosome 8p23.1, encoding Beta-defensin 104 (Q8WTQ1). Has antimicrobial activity.

Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 104, DEFB104A and DEFB104B, in head-to-head orientation. This gene, DEFB104A, represents the more centromeric copy.

Source: NCBI Gene 140596 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_080389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18115
Approved symbol	DEFB104A
Name	defensin beta 104A
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	DEFB4, DEFB-4
Ensembl gene	ENSG00000176782
Ensembl biotype	protein_coding
Entrez	140596

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000314265

RefSeq mRNA: 1 — MANE Select: NM_080389 NM_080389

CCDS: CCDS34834

Canonical transcript exons

ENST00000314265 — 2 exons

Exon	Start	End
ENSE00001674976	7836436	7836542
ENSE00001946329	7841034	7841242

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 71.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0089 / max 15.4890, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
205056	0.0089	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	71.14	gold quality
esophagus mucosa	UBERON:0002469	46.05	gold quality
endometrium	UBERON:0001295	40.01	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
esophagus	UBERON:0001043	33.66	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	30.20	gold quality
leukocyte	CL:0000738	29.96	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
vagina	UBERON:0000996	27.63	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
blood	UBERON:0000178	26.52	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
kidney	UBERON:0002113	24.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 14)

• Beta-defensin 104 displays antimicrobial activity against S. carnosus, E. coli, S. cerevisiae, and P. aeruginosa (strong). (PMID:11481241)
• There is an association of four common DEFB104 haplotypes with the risk of prostate cancer in two independent patient cohorts. (PMID:18515986)
• elevated DEFB4 copy number is a risk factor for Crohn’s disease (PMID:19809410)
• This study demonstrates, the involvement of NOD1 and DEFB4 in direct killing of Helicobacter pylori bacteria by epithelial cells and confirms the importance of NOD1 in host defence mechanisms against cagPAI(+)Helicobacter pylori infection. (PMID:20039881)
• The mRNA level of the beta defensin 4 did not differ significantly between the two subgroups. (PMID:20128731)
• Analysis of the DEFB4 promoter region shows remarkably high density of sequence variabilities. (PMID:20445567)
• Data show that beta-defensin cluster (DEFB4, DEFB103 and DEFB104) varied between 2 and 9 copies per genome, and high copy numbers (>4) were underrepresented among patients, suggesting that increased copy numbers could protect from CD. (PMID:20483368)
• We report here the application of small ubiquitin-related modifier (SUMO) fusion technology to the expression and purification of cationic antibacterial peptide hBD4. (PMID:20526896)
• The variations in the genes encoding human beta-defensin-1 and -2 may be associated with the risk of severe acute pancreatitis. (PMID:20720450)
• Our results suggest that copy number variation of DEFB4 may not contribute to the pathogenesis of Behcet’s disease. (PMID:21385545)
• Data suggest an activation of b-defensin-4 induction, in human knee meniscus by the osteoarthritis inflammatory process as a result of an endogenous antibiotic defense mechanism accompanied by an intrinsic effort of tissue remodeling. (PMID:21879330)
• TFF3 activated the epithelial cells in culture to produce beta defensins 2 (hBD2) and beta defensins 4 (PMID:23198942)
• there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer. (PMID:26038828)
• Expression of hBD-1, hBD-2, hBD-3, and hBD-4 in healthy and chronic periodontitis gingiva. (PMID:26874342)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Defb22	ENSMUSG00000027468
rattus_norvegicus	Defb22	ENSRNOG00000007525

Paralogs (19): DEFB127 (ENSG00000088782), DEFB129 (ENSG00000125903), DEFB118 (ENSG00000131068), DEFB104B (ENSG00000177023), DEFB125 (ENSG00000178591), DEFB124 (ENSG00000180383), DEFB123 (ENSG00000180424), DEFB119 (ENSG00000180483), DEFB108B (ENSG00000184276), DEFB128 (ENSG00000185982), DEFB131A (ENSG00000186146), DEFB132 (ENSG00000186458), DEFB121 (ENSG00000204548), DEFB134 (ENSG00000205882), DEFB135 (ENSG00000205883), DEFB108C (ENSG00000215371), DEFB116 (ENSG00000215545), DEFB115 (ENSG00000215547), DEFB131B (ENSG00000225805)

Protein

Protein identifiers

Beta-defensin 104 — Q8WTQ1 (reviewed: Q8WTQ1)

Alternative names: Beta-defensin 4, Defensin, beta 104

All UniProt accessions (1): Q8WTQ1

UniProt curated annotations — full annotation on UniProt →

Function. Has antimicrobial activity. Synergistic effects with lysozyme and DEFB103.

Subcellular location. Secreted.

Tissue specificity. High expression in the testis. Gastric antrum exhibited relatively high levels. A lower expression is observed in uterus and neutrophils thyroid gland, lung, and kidney. No detectable expression in other tissues tested.

Induction. Antimicrobial activity is decreased when the sodium chloride concentration is increased.

Similarity. Belongs to the beta-defensin family.

RefSeq proteins (2): NP_001409020, NP_525128* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025933	Beta_defensin_dom	Domain

Pfam: PF13841

UniProt features (11 total): strand 3, disulfide bond 3, signal peptide 1, peptide 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5KI9	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTQ1-F1	80.79	0.42

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): 30–57, 37–51, 41–58

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1461957	Beta defensins
R-HSA-1461973	Defensins

MSigDB gene sets: 37 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RESPONSE_TO_KETONE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_RESPONSE_TO_LIPID, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_CELLULAR_RESPONSE_TO_KETONE

GO Biological Process (8): monocyte chemotaxis (GO:0002548), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), positive chemotaxis (GO:0050918), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), defense response (GO:0006952), defense response to bacterium (GO:0042742)

GO Molecular Function (1): chemoattractant activity (GO:0042056)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Defensins	1
Antimicrobial peptides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	2
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
immune response	1
defense response to symbiont	1
chemotaxis	1
cellular response to lipid	1
cellular response to alcohol	1
cellular response to ketone	1
response to phorbol 13-acetate 12-myristate	1
response to stress	1
defense response	1
response to bacterium	1
receptor ligand activity	1
positive chemotaxis	1
cellular anatomical structure	1

Protein interactions and networks

STRING

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFB104A	DEFB103A	P81534	967
DEFB104A	DEFB1	P60022	916
DEFB104A	DEFB105A	Q8NG35	914
DEFB104A	DEFB4A	O15263	909
DEFB104A	DEFB106A	Q8N104	893
DEFB104A	DEFB107A	Q8IZN7	831
DEFB104A	A0A0G2JN59	A0A0G2JN59	771
DEFB104A	DEFB108B	Q8NET1	754
DEFB104A	DEFA1	P11479	712
DEFB104A	CAMP	P49913	623
DEFB104A	LTF	P02788	597
DEFB104A	HBD	P02042	579
DEFB104A	DEFA5	Q01523	532
DEFB104A	CCR6	P51684	526
DEFB104A	RNASE7	P80927	525

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DEFB104A	IFI30	psi-mi:“MI:0914”(association)	0.530
DEFB104A	HRAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): DEFB104B (Affinity Capture-MS), RMND1 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), IFI30 (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), HRAS (Affinity Capture-MS), PTPRG (Affinity Capture-MS), RMND1 (Affinity Capture-MS), IFI30 (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), DEFB104A (Affinity Capture-MS)

ESM2 similar proteins: A0A7G6KN55, A3RJ36, A4H202, A4H203, A4H204, O02775, O18794, O19038, O19039, O62697, O88514, O89117, O97946, P0C8A6, P0C8A7, P25068, P46162, P46163, P46165, P46168, P56386, P60022, P61261, P61262, P61263, P82019, Q28880, Q32ZI0, Q32ZI2, Q32ZI3, Q32ZI4, Q5IAB9, Q6GXJ1, Q6IV23, Q6QLQ9, Q6QLR3, Q7JGL8, Q7JGL9, Q7JGM0, Q7JGM1

Diamond homologs: A4H202, A4H203, A4H204, Q5IAB9, Q8WTQ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

121 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7836538:TCCAG:T	donor_loss	0.9400
8:7836539:CCAG:C	donor_loss	0.9400
8:7836540:CAGG:C	donor_loss	0.9400
8:7836541:AG:A	donor_loss	0.9400
8:7836542:GGTAA:G	donor_loss	0.9400
8:7836544:T:G	donor_loss	0.9300
8:7841032:A:AG	acceptor_gain	0.8800
8:7841033:G:GG	acceptor_gain	0.8800
8:7841033:GT:G	acceptor_gain	0.8600
8:7841033:GTGA:G	acceptor_gain	0.8100
8:7836552:G:T	donor_gain	0.8000
8:7836551:G:GT	donor_gain	0.6500
8:7836543:G:GG	donor_gain	0.6300
8:7836681:ATT:A	acceptor_gain	0.6300
8:7836681:ATTG:A	acceptor_gain	0.6000
8:7841031:TAGTG:T	acceptor_gain	0.5900
8:7841032:AGTGA:A	acceptor_gain	0.5900
8:7841033:GTGAG:G	acceptor_gain	0.5900
8:7837786:G:GT	donor_gain	0.5300
8:7841020:ATCCT:A	acceptor_loss	0.5300
8:7841021:T:G	acceptor_loss	0.5300
8:7841024:T:A	acceptor_loss	0.5300
8:7841029:TCTAG:T	acceptor_loss	0.5300
8:7841030:CTAGT:C	acceptor_loss	0.5300
8:7841032:A:AT	acceptor_loss	0.5300
8:7841032:AGT:A	acceptor_gain	0.5300
8:7841033:GTG:G	acceptor_gain	0.5300
8:7841019:T:G	acceptor_loss	0.5200
8:7841028:ATCT:A	acceptor_loss	0.5000
8:7836635:G:GT	donor_gain	0.4900

AlphaMissense

457 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7841063:T:A	C30S	0.956
8:7841064:G:C	C30S	0.956
8:7841084:T:A	C37S	0.956
8:7841085:G:C	C37S	0.956
8:7841126:T:A	C51S	0.953
8:7841127:G:C	C51S	0.953
8:7841161:G:C	W62C	0.952
8:7841161:G:T	W62C	0.952
8:7841126:T:C	C51R	0.949
8:7841064:G:A	C30Y	0.945
8:7841084:T:C	C37R	0.942
8:7841096:T:A	C41S	0.937
8:7841097:G:C	C41S	0.937
8:7841147:T:A	C58S	0.936
8:7841148:G:C	C58S	0.936
8:7841063:T:C	C30R	0.933
8:7841096:T:C	C41R	0.920
8:7841064:G:T	C30F	0.919
8:7841144:T:A	C57S	0.917
8:7841145:G:C	C57S	0.917
8:7841147:T:C	C58R	0.914
8:7841065:T:G	C30W	0.913
8:7841149:T:G	C58W	0.913
8:7841144:T:C	C57R	0.905
8:7841128:T:G	C51W	0.904
8:7841146:C:G	C57W	0.895
8:7841148:G:A	C58Y	0.895
8:7841086:C:G	C37W	0.892
8:7841145:G:A	C57Y	0.891
8:7841085:G:A	C37Y	0.882

dbSNP variants (sampled 300 via entrez): RS1003059324 (8:7837446 T>C), RS1007372848 (8:7840029 C>A,T), RS10089608 (8:7836263 T>A), RS1012549410 (8:7837274 G>A,T), RS1013599467 (8:7835728 C>A,T), RS1015730633 (8:7837510 T>C), RS1019624825 (8:7840378 A>G,T), RS1023184917 (8:7835915 T>C), RS1026994796 (8:7837941 C>T), RS1027565840 (8:7839915 C>T), RS1031558062 (8:7840610 C>G,T), RS1037207812 (8:7839802 C>G,T), RS1040228564 (8:7835052 G>C), RS1040259432 (8:7836741 G>A,C), RS1044089743 (8:7839684 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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