DEFB103A

Summary

DEFB103A (defensin beta 103A, HGNC:15967) is a protein-coding gene on chromosome 8p23.1, encoding Beta-defensin 103 (P81534). Exhibits antimicrobial activity against Gram-positive bacteria S.aureus and S.pyogenes, Gram-negative bacteria P.aeruginosa and E.coli and the yeast C.albicans.

Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 103, an antibiotic peptide which is induced by bacteria and interferon gamma, and which displays antimicrobial activity against S. aureus, S. pyogenes, P. aeruginosa, E. coli, and C. albicans.

Source: NCBI Gene 414325 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_001081551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15967
Approved symbol	DEFB103A
Name	defensin beta 103A
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	HBD-3, HBP-3, HBD3, HBP3, DEFB-3
Ensembl gene	ENSG00000176797
Ensembl biotype	protein_coding
Entrez	414325

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000314357

RefSeq mRNA: 2 — MANE Select: NM_001081551 NM_001081551, NM_001422090

CCDS: CCDS43701

Canonical transcript exons

ENST00000314357 — 2 exons

Exon	Start	End
ENSE00001621000	7882423	7882663
ENSE00001750653	7881392	7881479

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 86.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0204 / max 9.8523, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
205059	0.0204	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.16	silver quality
skin of leg	UBERON:0001511	60.80	gold quality
zone of skin	UBERON:0000014	58.78	gold quality
skin of abdomen	UBERON:0001416	55.84	gold quality
esophagus mucosa	UBERON:0002469	52.69	gold quality
tonsil	UBERON:0002372	50.20	gold quality
ectocervix	UBERON:0012249	49.17	gold quality
mucosa of transverse colon	UBERON:0004991	48.34	gold quality
vagina	UBERON:0000996	40.54	gold quality
sural nerve	UBERON:0015488	39.56	gold quality
esophagus	UBERON:0001043	38.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	38.24	gold quality
uterine cervix	UBERON:0000002	37.25	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
minor salivary gland	UBERON:0001830	36.20	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	36.10	gold quality
saliva-secreting gland	UBERON:0001044	35.57	gold quality
islet of Langerhans	UBERON:0000006	35.53	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
monocyte	CL:0000576	33.71	gold quality
leukocyte	CL:0000738	33.16	gold quality
muscle tissue	UBERON:0002385	33.06	gold quality
cortex of kidney	UBERON:0001225	31.79	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
vermiform appendix	UBERON:0001154	31.73	gold quality
kidney	UBERON:0002113	31.35	gold quality
adult mammalian kidney	UBERON:0000082	31.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	2.40
E-ANND-3	no	0.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG, TNF

Literature-anchored findings (GeneRIF, showing 22)

• The encoded peptide displays antimicrobial activity against S. aureus and E. faecium. (PMID:11085990)
• Inducibility of HBD3 influences the severity of Gram-positive skin infection in humans in vivo. (PMID:20404083)
• 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)
• Human pulmonary cells produce hBD-3 upon L. pneumophila infection via a TLR-JNK-AP-1-dependent pathway which may contribute to an efficient innate immune defense. (PMID:20615218)
• The beta-defensin antimicrobial peptides hBD1, hBD2 and hBD3 were expressed by immature dendritic cells as well as gingival epithelial cells. (PMID:20618959)
• PPARgamma regulates the 1,25D-induced hBD-3 and cathelicidin expression in keratinocytes through the regulation of AP-1 and p38 activity. (PMID:20970965)
• hBD3 represents a novel NF-kappaB-regulated mediator of CCR7 expression and anti-apoptotic pathways. (PMID:21071608)
• extraplacental membranes can react differentialy to the arrival of E. coli, secreting HBD2 and HBD3 mainly in the choriodecidua region. (PMID:21122132)
• hBD-1 might function as a tumor suppressor gene in oral squamous cell carcinoma, while hBD-2 and -3 might be protooncogenes. (PMID:21280982)
• Data show that high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes. (PMID:21442129)
• Human beta-defensin 3 exhibits further functions than antimicrobial peptide activity in cultured bone cells, including stimulation of proliferation and differentiation. (PMID:21520074)
• Using a large, unique cohort of pediatric CA-SAB, this study found no significant association between DEFB1 genetic variation or DEFB4/DEFB103 gene copy number and susceptibility for Staphylococcus aureus bacteremia (PMID:22384213)
• These results suggest an important role for hBD3 in inducing dendritic cell activation, migration, and polarization. (PMID:22951718)
• these observations suggest that there may be an interracial difference in DEFB4/103A copy numbers between admixed populations and a relationship between DEFB1 single nucleotide polymorphisms and DEFB4/103A copy number variation (PMID:23194186)
• Human beta-defensin 3 peptide is increased and redistributed in Crohn’s ileitis (PMID:23511030)
• Mapping of key residues in the interaction between human Beta-defensin 3 and CXCR4 reveals key defensin motifs involved in protein binding. (PMID:23659571)
• study demonstrates that HBD2 and 3 activate plasmacytoid dendritic cells by enhancing the intracellular uptake of CpG and self DNA and promote DNA-induced IFN-alpha production in a TLR9-dependent manner (PMID:23776172)
• It may be concluded hepatitis B virus up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of hepatitis B. (PMID:25196417)
• the role of DEFB103 gene copy number variation (CNV) in ankylosing spondylitis (AS) susceptibility, was investigated. (PMID:26224324)
• this study shows that hBD3 amplifies the response to bacterial DNA in both mouse and human immune cells in a TLR9-dependent manner (PMID:28102569)
• Results from study in human monocytic cell line THP-1 and murine macrophage-like cell line RAW264.7 demonstrate a novel immune defense activity of BD2 and BD3, which promotes clearance of Pseudomonas aeruginosa by inhibiting macrophage autophagy through down-regulation of EGR1 and c-FOS. (PMID:29487594)
• In aged skin the relative paucity of Langerhans cells not only results in diminished immunosurveillance, but could also reduce the epidermal pool of HBD3, potentially contributing to impaired cutaneous immunity to microbes and reduced efficacy of tumor cell lysis. (PMID:29758092)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Defb14	ENSMUSG00000046354
rattus_norvegicus	Defb14	ENSRNOG00000032304

Paralogs (1): DEFB103B (ENSG00000177243)

Protein

Protein identifiers

Beta-defensin 103 — P81534 (reviewed: P81534)

Alternative names: Beta-defensin 3, Defensin, beta 103, Defensin-like protein

All UniProt accessions (2): P81534, A0A894JZ42

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits antimicrobial activity against Gram-positive bacteria S.aureus and S.pyogenes, Gram-negative bacteria P.aeruginosa and E.coli and the yeast C.albicans. Kills multiresistant S.aureus and vancomycin-resistant E.faecium. No significant hemolytic activity was observed.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in skin and tonsils, and to a lesser extent in trachea, uterus, kidney, thymus, adenoid, pharynx and tongue. Low expression in salivary gland, bone marrow, colon, stomach, polyp and larynx. No expression in small intestine.

Induction. By bacterial infection and by IFNG/IFN-gamma.

Similarity. Belongs to the beta-defensin family.

RefSeq proteins (2): NP_001075020, NP_001409019 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001855	Defensin_beta-like	Domain

Pfam: PF00711

UniProt features (12 total): strand 4, disulfide bond 3, signal peptide 1, peptide 1, sequence conflict 1, turn 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1KJ6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P81534-F1	85.23	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): 33–62, 40–55, 45–63

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 38 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELL_CHEMOTAXIS, GOBP_TAXIS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_SYMBIONT, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_CELL_KILLING, GOBP_POSITIVE_CHEMOTAXIS, GOCC_GOLGI_LUMEN

GO Biological Process (9): killing of cells of another organism (GO:0031640), defense response to bacterium (GO:0042742), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), obsolete killing by host of symbiont cells (GO:0051873), cell chemotaxis (GO:0060326), defense response (GO:0006952), positive chemotaxis (GO:0050918), defense response to symbiont (GO:0140546)

GO Molecular Function (3): CCR6 chemokine receptor binding (GO:0031731), chemoattractant activity (GO:0042056), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796)

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
chemotaxis	2
cell killing	1
disruption of cell in another organism	1
defense response	1
response to bacterium	1
cell migration	1
cellular response to chemical stimulus	1
response to stress	1
defense response to other organism	1
CCR chemokine receptor binding	1
receptor ligand activity	1
positive chemotaxis	1
binding	1
cellular anatomical structure	1
Golgi apparatus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFB103A	CCR6	P51684	976
DEFB103A	CCR2	P41597	971
DEFB103A	DEFB104A	Q8WTQ1	967
DEFB103A	CCRL2	O00421	967
DEFB103A	DEFB1	P60022	953
DEFB103A	CXCR4	P30991	912
DEFB103A	DEFB105A	Q8NG35	880
DEFB103A	CAMP	P49913	873
DEFB103A	DEFB106A	Q8N104	861
DEFB103A	S100A7	P31151	849
DEFB103A	SLPI	P03973	837
DEFB103A	A0A0G2JN59	A0A0G2JN59	823
DEFB103A	ASIP	P42127	800
DEFB103A	RNASE7	P80927	790
DEFB103A	LCN2	P30150	770
DEFB103A	DEFB107A	Q8IZN7	770

IntAct

34 interactions, top by confidence:

A	B	Type	Score
DEFB103A	SPATA31A7	psi-mi:“MI:0915”(physical association)	0.560
	DEFB103A	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	DEFB103A	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	B3GALT5	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	EBP	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	ODF4	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
DEFB103A	AQP6	psi-mi:“MI:0915”(physical association)	0.560
SPATA31A7	DEFB103A	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A		psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	TMPRSS2	psi-mi:“MI:0915”(physical association)	0.000
B3GALT5	DEFB103A	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	EBP	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	SSMEM1	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	SCN3B	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	ODF4	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
DEFB103A	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): DEFB103A (Reconstituted Complex), DEFB103B (Reconstituted Complex), XOG1 (Reconstituted Complex), XOG1 (Reconstituted Complex), DEFB103A (Two-hybrid), DEFB103B (Two-hybrid), DEFB103A (Two-hybrid), DEFB103B (Two-hybrid), DEFB103A (Two-hybrid), DEFB103B (Two-hybrid), DEFB103A (Two-hybrid), DEFB103B (Two-hybrid), DEFB103A (Two-hybrid), DEFB103B (Two-hybrid), DEFB103A (Two-hybrid)

ESM2 similar proteins: A0A7G6KN55, A3RJ36, A4H1Z9, A4H200, A4H202, A4H203, A4H204, O02775, O15263, O19038, O19039, O62697, O88514, O89117, O97946, P0C8A6, P0C8A7, P25068, P46156, P46157, P46161, P46162, P46163, P46165, P46167, P46168, P46169, P56386, P80391, P81534, P82019, P83943, Q0E4V3, Q28880, Q32ZH7, Q32ZI0, Q32ZI3, Q32ZI4, Q6IV23, Q6IV26

Diamond homologs: A3RJ36, A4H200, O02775, O15263, O18815, O19038, O19039, O62697, O88514, O97946, P25068, P46159, P46160, P46161, P46162, P46163, P46164, P46165, P46166, P46167, P46168, P46169, P46170, P46171, P81534, P83943, P85150, Q0W9P9, Q28880, Q32ZI3, Q32ZI4, Q6QLR1, Q91V70, Q91V82, Q91VD6, Q95JD2, Q9BDS9, Q9TT12, Q9WTL0, A4H1Z9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	93

Top pathogenic / likely-pathogenic (0)

SpliceAI

78 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7881475:TCCAG:T	donor_loss	0.9800
8:7881476:CCAG:C	donor_loss	0.9800
8:7881477:CAG:C	donor_loss	0.9800
8:7881478:AGG:A	donor_loss	0.9800
8:7881479:GGTAA:G	donor_loss	0.9800
8:7881481:T:G	donor_loss	0.9800
8:7882419:GCAG:G	acceptor_loss	0.9800
8:7882421:A:AG	acceptor_gain	0.9800
8:7882421:AGG:A	acceptor_loss	0.9800
8:7882422:G:GG	acceptor_gain	0.9800
8:7882422:GGTC:G	acceptor_gain	0.9700
8:7882412:T:TA	acceptor_gain	0.9600
8:7882416:A:AG	acceptor_gain	0.9600
8:7882422:GGT:G	acceptor_gain	0.9600
8:7881420:C:G	donor_gain	0.9400
8:7882407:T:A	acceptor_gain	0.9300
8:7882422:GGTCA:G	acceptor_gain	0.9300
8:7882421:AG:A	acceptor_gain	0.9200
8:7882422:GG:G	acceptor_gain	0.9200
8:7882418:T:TA	acceptor_gain	0.9100
8:7881427:G:GT	donor_gain	0.9000
8:7882416:ATT:A	acceptor_gain	0.8900
8:7882417:T:G	acceptor_gain	0.8300
8:7881480:G:GG	donor_gain	0.8100
8:7882404:T:TA	acceptor_gain	0.7800
8:7881407:TG:T	donor_gain	0.7200
8:7882422:G:T	acceptor_gain	0.6200
8:7882421:A:G	acceptor_gain	0.6000
8:7882419:GCA:G	acceptor_gain	0.5900
8:7882420:CAGG:C	acceptor_gain	0.5700

AlphaMissense

420 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7882521:G:T	G53C	0.989
8:7882522:G:T	G53V	0.985
8:7882551:T:A	C63S	0.984
8:7882552:G:C	C63S	0.984
8:7882461:T:A	C33S	0.982
8:7882462:G:C	C33S	0.982
8:7882482:T:A	C40S	0.981
8:7882483:G:C	C40S	0.981
8:7882552:G:A	C63Y	0.979
8:7882462:G:A	C33Y	0.978
8:7882497:T:C	C45R	0.978
8:7882548:T:C	C62R	0.978
8:7882548:T:A	C62S	0.977
8:7882549:G:C	C62S	0.977
8:7882553:C:G	C63W	0.977
8:7882550:C:G	C62W	0.975
8:7882497:T:A	C45S	0.974
8:7882498:G:A	C45Y	0.974
8:7882498:G:C	C45S	0.974
8:7882527:T:A	C55S	0.974
8:7882527:T:C	C55R	0.974
8:7882528:G:C	C55S	0.974
8:7882463:C:G	C33W	0.973
8:7882521:G:C	G53R	0.973
8:7882551:T:C	C63R	0.973
8:7882461:T:C	C33R	0.972
8:7882482:T:C	C40R	0.969
8:7882462:G:T	C33F	0.968
8:7882552:G:T	C63F	0.967
8:7882476:G:T	G38C	0.966

dbSNP variants (sampled 300 via entrez): RS1005042169 (8:7879896 C>A), RS1009123684 (8:7880803 C>A,G), RS1019127165 (8:7880933 A>G,T), RS1028643476 (8:7880412 A>C), RS1036077680 (8:7879914 C>T), RS1036602312 (8:7883092 C>A), RS1046259478 (8:7883002 C>A), RS1056196764 (8:7879819 C>A,T), RS112876614 (8:7882748 C>A,T), RS1157528662 (8:7880479 T>A), RS1157531922 (8:7879557 T>A), RS1158160436 (8:7882894 T>C), RS1159076134 (8:7882905 C>A), RS1159290429 (8:7879627 T>C), RS1159325040 (8:7881109 G>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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Phenobarbital	affects expression	1
Rotenone	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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