DEFB123

Summary

DEFB123 (defensin beta 123, HGNC:18103) is a protein-coding gene on chromosome 20q11.21, encoding Beta-defensin 123 (Q8N688). Has antibacterial activity.

Defensins are cysteine-rich cationic polypeptides that are important in the host immunologic response to invading microorganisms. This antimicrobial protein is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20q11.1. Two transcript variants, one protein-coding and the other not, have been found for this gene.

Source: NCBI Gene 245936 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_153324

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18103
Approved symbol	DEFB123
Name	defensin beta 123
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	DEFB-23
Ensembl gene	ENSG00000180424
Ensembl biotype	protein_coding
OMIM	616076
Entrez	245936

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000376309

RefSeq mRNA: 1 — MANE Select: NM_153324 NM_153324

CCDS: CCDS13180

Canonical transcript exons

ENST00000376309 — 2 exons

Exon	Start	End
ENSE00001470131	31450029	31450257
ENSE00001906646	31440632	31440756

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 99.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1833 / max 224.1892, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183959	0.1833	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.24	gold quality
left testis	UBERON:0004533	99.21	gold quality
testis	UBERON:0000473	96.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.15	gold quality
adult organism	UBERON:0007023	83.78	gold quality
corpus epididymis	UBERON:0004359	80.87	gold quality
ileal mucosa	UBERON:0000331	76.21	silver quality
tibialis anterior	UBERON:0001385	65.37	silver quality
caput epididymis	UBERON:0004358	60.25	gold quality
deltoid	UBERON:0001476	57.42	gold quality
pancreatic ductal cell	CL:0002079	57.11	silver quality
quadriceps femoris	UBERON:0001377	54.37	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
epithelial cell of pancreas	CL:0000083	54.30	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
vastus lateralis	UBERON:0001379	52.79	gold quality
skin of hip	UBERON:0001554	50.64	silver quality
buccal mucosa cell	CL:0002336	50.27	gold quality
myocardium	UBERON:0002349	50.25	gold quality
biceps brachii	UBERON:0001507	49.02	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
skeletal muscle tissue	UBERON:0001134	45.94	gold quality
muscle tissue	UBERON:0002385	45.13	gold quality
cauda epididymis	UBERON:0004360	43.95	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
jejunum	UBERON:0002115	42.77	gold quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	1394.21
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

Literature-anchored findings (GeneRIF, showing 1)

• The protein encoded by this gene is thought to display antimicrobial activity. (PMID:15772680)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Defb36	ENSMUSG00000044863
rattus_norvegicus	Defb36	ENSRNOG00000088915

Paralogs (19): DEFB127 (ENSG00000088782), DEFB129 (ENSG00000125903), DEFB118 (ENSG00000131068), DEFB104A (ENSG00000176782), DEFB104B (ENSG00000177023), DEFB125 (ENSG00000178591), DEFB124 (ENSG00000180383), 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 123 — Q8N688 (reviewed: Q8N688)

Alternative names: Beta-defensin 23, Defensin, beta 123

All UniProt accessions (1): Q8N688

UniProt curated annotations — full annotation on UniProt →

Function. Has antibacterial activity.

Subcellular location. Secreted.

Tissue specificity. Abundant expression in the male reproductive tract only. Abundant expressed in testis and the caput region of epididymis, but low in the corpus region.

Similarity. Belongs to the beta-defensin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N688-1	1	yes
Q8N688-2	2

RefSeq proteins (1): NP_697019* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025933	Beta_defensin_dom	Domain
IPR050544	Beta-defensin	Family

Pfam: PF13841

UniProt features (7 total): disulfide bond 3, splice variant 2, signal peptide 1, peptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N688-F1	83.83	0.49

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): 25–52, 32–46, 36–53

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 15 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, chr20q11, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_CELL_KILLING, GOBP_RESPONSE_TO_BACTERIUM, REACTOME_ANTIMICROBIAL_PEPTIDES, GSE13738_RESTING_VS_BYSTANDER_ACTIVATED_CD4_TCELL_UP, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERSPECIES_INTERACTION_BETWEEN_ORGANISMS, GOBP_DISRUPTION_OF_ANATOMICAL_STRUCTURE_IN_ANOTHER_ORGANISM, GOMF_MEMBRANE_DESTABILIZING_ACTIVITY, REACTOME_DEFENSINS, REACTOME_BETA_DEFENSINS, GSE16385_IFNG_TNF_VS_ROSIGLITAZONE_STIM_MACROPHAGE_DN

GO Biological Process (4): innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response (GO:0006952), defense response to bacterium (GO:0042742)

GO Molecular Function (0):

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
immune response	1
defense response to symbiont	1
defense response to bacterium	1
response to stress	1
defense response	1
response to bacterium	1
cellular anatomical structure	1

Protein interactions and networks

STRING

355 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFB123	DEFB116	Q30KQ4	672
DEFB123	DEFB125	Q8N687	628
DEFB123	DEFB115	Q30KQ5	585
DEFB123	CHCT1	Q86WR6	571
DEFB123	DEFB124	Q8NES8	559
DEFB123	DEFB108B	Q8NET1	528
DEFB123	DEFB128	Q7Z7B8	511
DEFB123	DEFB129	Q9H1M3	507
DEFB123	CT45A10	P0DMU9	506
DEFB123	CCDC160	A6NGH7	449
DEFB123	DEFB131A	P59861	433
DEFB123	DEFB126	Q9BYW3	427
DEFB123	SPATA4	Q8NEY3	411
DEFB123	SLC25A53	Q5H9E4	405
DEFB123	ZCCHC3	Q9NUD5	400

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DEFB123	PFDN6	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): CACNA2D1 (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PFDN2 (Affinity Capture-MS), PFDN4 (Affinity Capture-MS), PFDN5 (Affinity Capture-MS), PFDN6 (Affinity Capture-MS), CTBS (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), LDLR (Affinity Capture-MS), LRP4 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), VBP1 (Affinity Capture-MS)

ESM2 similar proteins: A3RJ36, A4H1Z9, A4H200, A4H235, A4H236, O02775, O15263, O19038, O19039, O62697, O88514, O97946, P25068, P46156, P46157, P46158, P46165, P46168, P61261, P61262, P80391, P80392, P81534, P83943, Q0E4V3, Q0W9P9, Q28880, Q30KK5, Q30KP9, Q32ZF7, Q32ZF8, Q32ZH7, Q32ZI3, Q32ZI4, Q5J5D0, Q6QLR1, Q6QLR3, Q7JGL8, Q7TNV7, Q7TNV9

Diamond homologs: A4H235, A4H236, Q30KK5, Q30KK6, Q30KL1, Q30KQ4, Q5J5C9, Q5J5D0, Q5J5Z9, Q5J600, Q8K3U4, Q8N688, A4H220, A4H221, A4H222, A4H223, A4H225, A4H226, A4H227, A4H228, Q30KK9, Q30KP9, Q5J602, Q8K3I8, Q8N690, Q95LI0, Q96PH6, Q32ZG3, Q8BGW9, A4H211, A4H212, A4H213, A4H253, A4H254, A4H255, Q30KJ4, Q30KN8, Q32ZG7, Q5IAB3, Q7Z7B8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

199 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31440752:TCCAG:T	donor_loss	0.9800
20:31440753:CCAGG:C	donor_loss	0.9800
20:31440754:CAGGT:C	donor_loss	0.9800
20:31440755:AG:A	donor_loss	0.9800
20:31440756:GGTAA:G	donor_loss	0.9800
20:31440757:GTA:G	donor_loss	0.9800
20:31440758:T:G	donor_loss	0.9800
20:31450025:TCA:T	acceptor_loss	0.9700
20:31450026:CAGGT:C	acceptor_loss	0.9700
20:31450027:A:C	acceptor_loss	0.9700
20:31450028:G:C	acceptor_loss	0.9700
20:31450016:T:TA	acceptor_gain	0.9600
20:31450016:T:A	acceptor_loss	0.9500
20:31450028:GGT:G	acceptor_gain	0.9400
20:31450023:T:TA	acceptor_gain	0.9300
20:31440978:G:GT	donor_gain	0.9200
20:31450021:T:A	acceptor_gain	0.9200
20:31450027:A:AG	acceptor_gain	0.9200
20:31450028:G:GG	acceptor_gain	0.9200
20:31450021:T:TA	acceptor_loss	0.9000
20:31450027:AGGT:A	acceptor_gain	0.9000
20:31450028:GGTG:G	acceptor_gain	0.9000
20:31440777:G:GT	donor_gain	0.7800
20:31448808:TTC:T	donor_gain	0.7300
20:31440759:A:C	donor_loss	0.6900
20:31450027:AGGTG:A	acceptor_gain	0.6900
20:31450028:GGTGG:G	acceptor_gain	0.6900
20:31450025:TCAGG:T	acceptor_gain	0.6800
20:31449995:T:TG	acceptor_loss	0.6700
20:31450026:CAGG:C	acceptor_gain	0.6500

AlphaMissense

426 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31450048:G:C	W26C	0.994
20:31450048:G:T	W26C	0.994
20:31450058:G:T	G30C	0.992
20:31450124:T:A	C52S	0.988
20:31450125:G:C	C52S	0.988
20:31450043:T:A	C25S	0.984
20:31450044:G:C	C25S	0.984
20:31450059:G:T	G30V	0.984
20:31450064:T:A	C32S	0.983
20:31450065:G:C	C32S	0.983
20:31450059:G:A	G30D	0.981
20:31450126:C:G	C52W	0.978
20:31450106:T:A	C46S	0.975
20:31450107:G:C	C46S	0.975
20:31450108:C:G	C46W	0.975
20:31450107:G:A	C46Y	0.974
20:31450076:T:A	C36S	0.973
20:31450077:G:C	C36S	0.973
20:31450124:T:C	C52R	0.973
20:31450127:T:A	C53S	0.973
20:31450128:G:C	C53S	0.973
20:31450045:C:G	C25W	0.972
20:31450125:G:A	C52Y	0.971
20:31450043:T:C	C25R	0.968
20:31450064:T:C	C32R	0.965
20:31450106:T:C	C46R	0.965
20:31450125:G:T	C52F	0.965
20:31450128:G:A	C53Y	0.964
20:31450066:C:G	C32W	0.962
20:31450044:G:A	C25Y	0.961

dbSNP variants (sampled 300 via entrez): RS1000418481 (20:31439989 A>T), RS1000534735 (20:31438870 T>G), RS1001215043 (20:31448706 C>CAT), RS1001464290 (20:31446339 A>C), RS1001578778 (20:31446582 T>C), RS1001690792 (20:31441251 C>T), RS1001796608 (20:31447815 C>G,T), RS1001807452 (20:31440088 G>A), RS1002089520 (20:31439897 T>A), RS1002099744 (20:31442697 C>T), RS1002550961 (20:31441432 G>A), RS1002871271 (20:31449636 C>T), RS1004034425 (20:31444512 T>C), RS1004107870 (20:31442765 C>T), RS1004588352 (20:31439364 A>G)

Disease associations

OMIM: gene MIM:616076 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004639_6	Prudent dietary pattern	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

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 S	affects cotreatment, decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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