DEFB4B

Summary

DEFB4B (defensin beta 4B, HGNC:30193) is a protein-coding gene on chromosome 8p23.1, encoding Defensin beta 4A (O15263). Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria, with highest activity against Gram-negative bacteria.

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 4, an antibiotic peptide which is locally regulated by inflammation.

Source: NCBI Gene 100289462 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_001205266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30193
Approved symbol	DEFB4B
Name	defensin beta 4B
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177257
Ensembl biotype	protein_coding
Entrez	100289462

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000318157

RefSeq mRNA: 1 — MANE Select: NM_001205266 NM_001205266

CCDS: CCDS55193

Canonical transcript exons

ENST00000318157 — 2 exons

Exon	Start	End
ENSE00001646530	7414855	7415097
ENSE00001753483	7416770	7416863

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 70.31.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	70.31	gold quality
tonsil	UBERON:0002372	41.59	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
muscle tissue	UBERON:0002385	34.66	gold quality
esophagus mucosa	UBERON:0002469	34.66	gold quality
right uterine tube	UBERON:0001302	34.12	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
sural nerve	UBERON:0015488	30.93	gold quality
islet of Langerhans	UBERON:0000006	30.28	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
urinary bladder	UBERON:0001255	29.20	silver quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
esophagus	UBERON:0001043	29.00	gold quality
liver	UBERON:0002107	28.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	28.64	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	28.01	gold quality
leukocyte	CL:0000738	27.97	gold quality
lymph node	UBERON:0000029	27.57	gold quality
blood	UBERON:0000178	26.88	gold quality
pancreas	UBERON:0001264	26.73	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
endometrium	UBERON:0001295	26.07	gold quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, RELA

Literature-anchored findings (GeneRIF, showing 3)

• DEFB4B expression is significantly downregulated in healthy palatal mucosa of smokers (PMID:31682009)
• Human beta-Defensin 2 Mutations Are Associated With Asthma and Atopy in Children and Its Application Prevents Atopic Asthma in a Mouse Model. (PMID:33717182)
• The encoded peptide has antimicrobial activity against E.coli, S. aureus, and P. aeruginosa. (PMID:9727055)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Defb3	ENSMUSG00000039775
mus_musculus	Defb4	ENSMUSG00000059230
rattus_norvegicus	Defb4	ENSRNOG00000013939
rattus_norvegicus	Defb3	ENSRNOG00000038126

Paralogs (6): DEFB4A (ENSG00000171711), DEFB109C (ENSG00000205989), DEFB109B (ENSG00000206034), DEFB130A (ENSG00000232948), DEFB130B (ENSG00000233050), DEFB109D (ENSG00000254866)

Protein

Protein identifiers

Defensin beta 4A — O15263 (reviewed: O15263)

Alternative names: Beta-defensin 2, Defensin, beta 2, Skin-antimicrobial peptide 1

All UniProt accessions (1): O15263

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria, with highest activity against Gram-negative bacteria. Antimicrobial activity against P.aruginosa seems to be salt-sensitive and is reduced with high salt concentrations greater than 25 mM. Also exhibits antimicrobial activity against the yeast C.albicans. Permeabilizes C.albicans cell membranes via targeting plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), thereby leading to cell fragmentation and cell death. Acts as a ligand for C-C chemokine receptor CCR6. Binds to CCR6 and induces chemotactic activity of CCR6-expressing cells, such as immature dendritic cells and memory T cells.

Subunit / interactions. Monomer. Homodimer.

Subcellular location. Secreted.

Tissue specificity. Expressed in lung epithelial cells (at protein level). Expressed in foreskin, lung and trachea. Lower expression in kidney, uterus and salivary gland tissue. Expressed in epithelial cells of the respiratory tract, with higher expression in distal parenchyma of the lung, trachea, and tonsils, and lower expression in pharynx and adenoid, and low expression in tongue and larynx.

Induction. Up-regulated by TNF, IL1B, Gram-negative and Gram-positive bacteria, C.albicans and bacterial lipopolysaccharides (LPS). Up-regulated by inflammation in skin keratinocytes in epidermal tissue.

Similarity. Belongs to the beta-defensin family. LAP/TAP subfamily.

RefSeq proteins (1): NP_001192195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001855	Defensin_beta-like	Domain
IPR006080	Beta/alpha-defensin_C	Domain

Pfam: PF00711

UniProt features (18 total): mutagenesis site 6, strand 5, disulfide bond 3, signal peptide 1, peptide 1, helix 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1FD3	X-RAY DIFFRACTION	1.35
1FD4	X-RAY DIFFRACTION	1.7
6CS9	X-RAY DIFFRACTION	1.85
1E4Q	SOLUTION NMR
1FQQ	SOLUTION NMR
8YD6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15263-F1	78.53	0.00

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): 31–60, 38–53, 43–61

Mutagenesis-validated functional residues (6):

Position	Phenotype
48	loss of pip2 binding and reduced liposomal lysis activity. impaired antifungal activity. decrease in fungal cell permeab
59	no impact on pip binding and liposomal lysis activity. lack of antifungal activity. lack of fungal cell permeabilization
33	loss of pip2 binding and loss of liposomal lysis activity. decrease in fungal cell permeabilization. impaired antifungal
45	loss of pip2 binding and loss of liposomal lysis activity. decrease in fungal cell permeabilization. impaired antifungal
46	no impact on fungal cell permeabilization. impaired antifungal activity.
47	no impact on fungal cell permeabilization. no impact on antifungal activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 9 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, YOSHIMURA_MAPK8_TARGETS_UP, REACTOME_ANTIMICROBIAL_PEPTIDES, WP_NONGENOMIC_ACTIONS_OF_125DIHYDROXYVITAMIN_D3, WP_VITAMIN_D_RECEPTOR_PATHWAY, WP_IL26_SIGNALING, REACTOME_DEFENSINS, REACTOME_BETA_DEFENSINS, chr8p23

GO Biological Process (14): chemotaxis (GO:0006935), immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), 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), defense response to fungus (GO:0050832), cell chemotaxis (GO:0060326), antifungal innate immune response (GO:0061760), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response (GO:0006952), positive chemotaxis (GO:0050918), defense response to symbiont (GO:0140546)

GO Molecular Function (4): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), 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	2
defense response to bacterium	2
chemotaxis	2
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
cell killing	1
disruption of cell in another organism	1
response to bacterium	1
response to fungus	1
cell migration	1
cellular response to chemical stimulus	1
innate immune response	1
defense response to fungus	1
antimicrobial humoral response	1
response to stress	1
defense response to other organism	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	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

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFB4B	CCR6	P51684	995
DEFB4B	CCRL2	O00421	994
DEFB4B	TLR4	O00206	986
DEFB4B	DEFB1	P60022	980
DEFB4B	CAMP	P49913	921
DEFB4B	CCR2	P41597	910
DEFB4B	DEFB104A	Q8WTQ1	909
DEFB4B	S100A7	P31151	889
DEFB4B	DEFA1	P11479	884
DEFB4B	DEFA5	Q01523	820
DEFB4B	DEFA1	P11479	796
DEFB4B	A0A0G2JN59	A0A0G2JN59	784
DEFB4B	RNASE7	P80927	782
DEFB4B	DEFA6	Q01524	774
DEFB4B	TLR2	O60603	758

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DEFB4A	ZMPSTE24	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (5): DEFB4A (Affinity Capture-Western), DEFB4A (Reconstituted Complex), ZMPSTE24 (Affinity Capture-MS), DEFB4A (Co-crystal Structure), ZMPSTE24 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

109 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7415097:CCTAA:C	acceptor_loss	0.9900
8:7415098:C:CA	acceptor_loss	0.9900
8:7416764:TCTCA:T	donor_loss	0.9900
8:7416765:CTCA:C	donor_loss	0.9900
8:7416766:TCAC:T	donor_loss	0.9900
8:7416768:ACCTG:A	donor_loss	0.9900
8:7416769:C:A	donor_loss	0.9900
8:7415094:ACAC:A	acceptor_gain	0.9800
8:7415095:CAC:C	acceptor_gain	0.9800
8:7415095:CACC:C	acceptor_gain	0.9800
8:7415098:C:CC	acceptor_gain	0.9700
8:7415095:CACCT:C	acceptor_gain	0.9600
8:7415096:AC:A	acceptor_gain	0.9600
8:7415096:ACC:A	acceptor_gain	0.9600
8:7415097:CC:C	acceptor_gain	0.9600
8:7415097:CCTA:C	acceptor_gain	0.9600
8:7415098:CT:C	acceptor_gain	0.9600
8:7415099:T:A	acceptor_gain	0.9600
8:7415094:ACACC:A	acceptor_gain	0.9500
8:7415093:AACAC:A	acceptor_gain	0.9400
8:7415102:C:CT	acceptor_gain	0.9400
8:7415103:A:T	acceptor_gain	0.9200
8:7415098:C:T	acceptor_gain	0.8900
8:7416391:T:C	donor_gain	0.8800
8:7416768:A:AC	donor_gain	0.8800
8:7416769:C:CC	donor_gain	0.8800
8:7416395:CAAG:C	donor_gain	0.8700
8:7415115:C:CT	acceptor_gain	0.8600
8:7416334:A:C	donor_gain	0.8200
8:7416818:AG:A	donor_gain	0.8200

AlphaMissense

413 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000616016 (8:7416389 T>C), RS1000756681 (8:7417368 G>A), RS1001216156 (8:7894039 G>A), RS1001248955 (8:7894898 C>T), RS1005780999 (8:7895050 T>C,G), RS1005815140 (8:7896809 G>A), RS1008132089 (8:7416008 G>A,T), RS1008578167 (8:7414469 A>C,G), RS10089609 (8:7415612 T>C), RS10089746 (8:7415725 T>A,C,G), RS1011403267 (8:7893646 C>G), RS1011989519 (8:7417515 A>C,T), RS1012452326 (8:7418748 A>C,T), RS1014609180 (8:7417926 G>A,C), RS1018454619 (8:7895175 C>A)

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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases reaction, decreases expression	1
Cadmium	decreases expression, increases abundance	1
Smoke	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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