DEFB104B

Summary

DEFB104B (defensin beta 104B, HGNC:26165) 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, DEFB104B, represents the more telomeric copy.

Source: NCBI Gene 503618 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_001040702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26165
Approved symbol	DEFB104B
Name	defensin beta 104B
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177023
Ensembl biotype	protein_coding
Entrez	503618

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000316169

RefSeq mRNA: 1 — MANE Select: NM_001040702 NM_001040702

CCDS: CCDS34812

Canonical transcript exons

ENST00000316169 — 2 exons

Exon	Start	End
ENSE00001676217	7475011	7475082
ENSE00001885132	7470308	7470516

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 85.53.

Top tissues by expression

119 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	85.53	silver quality
lower esophagus mucosa	UBERON:0035834	58.71	gold quality
esophagus mucosa	UBERON:0002469	42.86	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
ectocervix	UBERON:0012249	36.45	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
esophagus	UBERON:0001043	32.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
uterine cervix	UBERON:0000002	31.83	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
endometrium	UBERON:0001295	30.88	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.26	gold quality
vagina	UBERON:0000996	29.20	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
monocyte	CL:0000576	28.54	gold quality
leukocyte	CL:0000738	28.46	silver quality
urinary bladder	UBERON:0001255	28.18	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
saliva-secreting gland	UBERON:0001044	26.67	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Beta-defensin 104 displays antimicrobial activity against S. carnosus, E. coli, S. cerevisiae, and P. aeruginosa (strong). (PMID:11481241)
• 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)

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), DEFB104A (ENSG00000176782), 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_001035792, NP_001409020 (=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: 35 (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
DEFB104B	DEFB103A	P81534	967
DEFB104B	DEFB1	P60022	916
DEFB104B	DEFB105A	Q8NG35	914
DEFB104B	DEFB4A	O15263	909
DEFB104B	DEFB106A	Q8N104	893
DEFB104B	DEFB107A	Q8IZN7	831
DEFB104B	A0A0G2JN59	A0A0G2JN59	771
DEFB104B	DEFB108B	Q8NET1	754
DEFB104B	DEFA1	P11479	712
DEFB104B	CAMP	P49913	623
DEFB104B	LTF	P02788	597
DEFB104B	HBD	P02042	579
DEFB104B	DEFA5	Q01523	532
DEFB104B	CCR6	P51684	526
DEFB104B	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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

117 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7475005:TTTTA:T	donor_loss	0.9500
8:7475006:TTTA:T	donor_loss	0.9500
8:7475007:TTA:T	donor_loss	0.9500
8:7475008:TA:T	donor_loss	0.9500
8:7475009:A:T	donor_loss	0.9500
8:7475010:CCT:C	donor_loss	0.9500
8:7470517:C:CC	acceptor_gain	0.8800
8:7470515:CA:C	acceptor_gain	0.8600
8:7470513:CTCA:C	acceptor_gain	0.8100
8:7475001:C:A	donor_gain	0.8000
8:7475011:C:A	donor_loss	0.6900
8:7475009:A:AC	donor_gain	0.6800
8:7475010:C:CC	donor_gain	0.6800
8:7470512:TCTCA:T	acceptor_gain	0.5600
8:7470513:CTCAC:C	acceptor_gain	0.5600
8:7470514:TCACT:T	acceptor_gain	0.5600
8:7473767:T:TA	donor_gain	0.5500
8:7470514:TCA:T	acceptor_gain	0.5100
8:7470514:TCAC:T	acceptor_loss	0.5100
8:7470515:CAC:C	acceptor_gain	0.5100
8:7470516:ACTA:A	acceptor_loss	0.5100
8:7470517:C:CA	acceptor_loss	0.5100
8:7470518:T:G	acceptor_loss	0.5100
8:7470525:CAGGA:C	acceptor_loss	0.5100
8:7470526:A:T	acceptor_loss	0.5100
8:7470529:A:C	acceptor_loss	0.5100
8:7470519:A:C	acceptor_loss	0.5000
8:7470521:A:C	acceptor_loss	0.4900
8:7470531:A:C	acceptor_loss	0.4900
8:7474868:CCAA:C	acceptor_gain	0.4900

AlphaMissense

457 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1003460471 (8:7473220 G>A,C), RS1003491319 (8:7471807 C>G), RS1007296524 (8:7473887 C>T), RS1007349215 (8:7474374 A>G), RS1011220113 (8:7477072 C>G), RS1011662962 (8:7476282 A>C,G), RS1012894308 (8:7471679 A>G), RS1017221705 (8:7473895 A>G,T), RS1017274230 (8:7474378 G>C), RS1021799599 (8:7475051 C>A,T), RS1021853592 (8:7476375 G>A,T), RS1022991304 (8:7471786 G>T), RS1027511518 (8:7473805 A>T), RS1027785080 (8:7472173 A>C,G), RS1031360526 (8:7474649 A>C)

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
bisphenol F	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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