DEFB118

Summary

DEFB118 (defensin beta 118, HGNC:16196) is a protein-coding gene on chromosome 20q11.21, encoding Defensin beta 118 (Q96PH6). Host defense peptide that exhibits antimicrobial activity against both Gram-negative bacteria, such as E.coli and S.typhimurium, and Gram-positive bacteria, such as S.aureus and B.subtilis.

This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. Expression of this gene is regulated by androgen, and the encoded protein binds to sperm and exhibits antibacterial activity against E. coli. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20.

Source: NCBI Gene 117285 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_054112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16196
Approved symbol	DEFB118
Name	defensin beta 118
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ1018D12.3, DEFB-18, ESC42
Ensembl gene	ENSG00000131068
Ensembl biotype	protein_coding
OMIM	607650
Entrez	117285

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000253381

RefSeq mRNA: 1 — MANE Select: NM_054112 NM_054112

CCDS: CCDS13177

Canonical transcript exons

ENST00000253381 — 2 exons

Exon	Start	End
ENSE00000898434	31368601	31368708
ENSE00001301255	31372857	31373923

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 99.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4443 / max 782.1952, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183958	0.4443	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.29	gold quality
lateral globus pallidus	UBERON:0002476	84.12	gold quality
cardia of stomach	UBERON:0001162	83.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.21	gold quality
vena cava	UBERON:0004087	83.20	gold quality
epididymis	UBERON:0001301	82.63	gold quality
subthalamic nucleus	UBERON:0001906	81.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	81.50	gold quality
substantia nigra pars compacta	UBERON:0001965	80.80	gold quality
dorsal plus ventral thalamus	UBERON:0001897	80.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	80.30	gold quality
inferior vagus X ganglion	UBERON:0005363	79.15	gold quality
ventral tegmental area	UBERON:0002691	79.00	gold quality
body of tongue	UBERON:0011876	78.74	gold quality
tongue	UBERON:0001723	78.41	gold quality
superior surface of tongue	UBERON:0007371	78.41	gold quality
cerebellar vermis	UBERON:0004720	78.37	gold quality
thymus	UBERON:0002370	78.06	gold quality
medulla oblongata	UBERON:0001896	78.03	gold quality
superior vestibular nucleus	UBERON:0007227	78.00	gold quality
pericardium	UBERON:0002407	77.81	gold quality
trachea	UBERON:0003126	77.61	gold quality
pons	UBERON:0000988	77.58	gold quality
pylorus	UBERON:0001166	77.49	gold quality
saphenous vein	UBERON:0007318	77.33	gold quality
pharyngeal mucosa	UBERON:0000355	77.20	gold quality
superficial temporal artery	UBERON:0001614	76.73	gold quality
nipple	UBERON:0002030	76.62	gold quality
renal medulla	UBERON:0000362	76.54	gold quality
epithelium of nasopharynx	UBERON:0001951	76.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.13
E-HCAD-38	no	3024.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting DEFB118, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-8066	99.05	68.66	1532

Literature-anchored findings (GeneRIF, showing 2)

• DEFB118 may contribute to epididymal innate immunity and provide antimicrobial activity against microorganisms attacking sperm in the male and female reproductive tracts. (PMID:15033915)
• The truncated human beta-defensin 118 can modulate lipopolysaccharide mediated inflammatory response in RAW264.7 macrophages. (PMID:33181266)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Defb21	ENSMUSG00000056544
rattus_norvegicus	Defb21	ENSRNOG00000023154

Paralogs (19): DEFB127 (ENSG00000088782), DEFB129 (ENSG00000125903), DEFB104A (ENSG00000176782), 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

Defensin beta 118 — Q96PH6 (reviewed: Q96PH6)

Alternative names: Beta-defensin 18, Epididymal secretory protein 13.6

All UniProt accessions (2): Q96PH6, A0A384MTK2

UniProt curated annotations — full annotation on UniProt →

Function. Host defense peptide that exhibits antimicrobial activity against both Gram-negative bacteria, such as E.coli and S.typhimurium, and Gram-positive bacteria, such as S.aureus and B.subtilis. Inhibits cell adhesion of E.coli on intestinal epithelial enterocytes. Causes rapid permeabilization of both the outer and inner membrane of E.coli, leading to morphological alterations on the bacterial surface. Binds to bacterial lipopolysaccharides (LPS) with high affinity, and may thereby be involved in immunoregulation through LPS neutralization. May contribute to epididymal innate immunity and protect the sperm against attack by microorganisms.

Subcellular location. Secreted.

Tissue specificity. High-level and epididymis-specific expression. Most abundant in the epithelium of the caput and present in the epididymis lumen and bound to sperm. Also expressed in pancreas.

Post-translational modifications. The three-dimensional structure formed by the three intramolecular disulfide bridges is indispensable for antimicrobial activity.

Similarity. Belongs to the beta-defensin family.

RefSeq proteins (1): NP_473453* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025933	Beta_defensin_dom	Domain
IPR050544	Beta-defensin	Family

Pfam: PF13841

UniProt features (10 total): disulfide bond 3, compositionally biased region 2, signal peptide 1, peptide 1, propeptide 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PH6-F1	63.26	0.18

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): 27–54, 34–48, 38–55

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 60 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_LIPOPOLYSACCHARIDE_MEDIATED_SIGNALING_PATHWAY, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_RESPONSE_TO_LIPID, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_LIPOPOLYSACCHARIDE_MEDIATED_SIGNALING_PATHWAY

GO Biological Process (11): cell-matrix adhesion (GO:0007160), negative regulation of cell adhesion (GO:0007162), spermatogenesis (GO:0007283), killing of cells of another organism (GO:0031640), negative regulation of lipopolysaccharide-mediated signaling pathway (GO:0031665), defense response to bacterium (GO:0042742), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response (GO:0006952)

GO Molecular Function (3): lipopolysaccharide binding (GO:0001530), membrane destabilizing activity (GO:0140912), protein binding (GO:0005515)

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
cell-substrate adhesion	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
developmental process involved in reproduction	1
male gamete generation	1
cell killing	1
disruption of cell in another organism	1
negative regulation of response to biotic stimulus	1
negative regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
negative regulation of response to external stimulus	1
defense response	1
response to bacterium	1
immune response	1
defense response to symbiont	1
antimicrobial humoral response	1
response to stress	1
lipid binding	1
carbohydrate derivative binding	1
molecular_function	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFB118	DEFB126	Q9BYW3	749
DEFB118	DEFB129	Q9H1M3	726
DEFB118	DEFB114	Q30KQ6	710
DEFB118	DEFB127	Q9H1M4	665
DEFB118	DEFB116	Q30KQ4	652
DEFB118	DEFB115	Q30KQ5	611
DEFB118	DEFB132	Q7Z7B7	607
DEFB118	DEFB1	P60022	580
DEFB118	DEFB131A	P59861	576
DEFB118	A0A0G2JN59	A0A0G2JN59	518
DEFB118	DEFB108B	Q8NET1	506
DEFB118	EGF	P01133	492
DEFB118	WFDC9	Q8NEX5	480
DEFB118	DEFB104A	Q8WTQ1	475
DEFB118	DEFB105A	Q8NG35	470

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GUCA1A	DEFB118	psi-mi:“MI:0915”(physical association)	0.560
DEFB118	IFI30	psi-mi:“MI:0914”(association)	0.350
GUCA1A	DEFB118	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): DEFB118 (Two-hybrid), THOP1 (Affinity Capture-MS), IFI30 (Affinity Capture-MS)

ESM2 similar proteins: A4H220, A4H221, A4H222, A4H223, A4H225, A4H227, A4H228, A4H238, A4H240, A4H253, A4H254, A4H255, A4H257, A4H258, A4H259, A4H262, A4H263, A4H264, A4H265, P0C8A8, P0DY26, P0DY27, Q29RT9, Q30KJ7, Q30KK0, Q30KK1, Q30KK9, Q30KL1, Q30KL7, Q30KP3, Q30KP5, Q30KQ4, Q30KQ5, Q30KQ8, Q30KR1, Q30KT5, Q32P86, Q32ZH2, Q32ZH6, Q3UW43

Diamond homologs: A4H220, A4H221, A4H222, A4H223, P0C8A5, Q30KK6, Q30KK9, Q30KQ5, Q5J5C9, Q95LI0, Q96PH6, P0C8A6, A4H225, A4H226, A4H227, A4H228, A4H235, A4H236, Q30KK5, Q30KP9, Q5J5D0, Q5J600, Q5J602, Q8K3I8, Q8N688, Q8N690

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

235 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31369170:G:GG	donor_gain	0.9800
20:31369178:C:G	donor_gain	0.9800
20:31372855:A:AG	acceptor_gain	0.9800
20:31372856:G:GG	acceptor_gain	0.9800
20:31368707:AGGTA:A	donor_loss	0.9700
20:31368708:G:GA	donor_loss	0.9700
20:31368709:GTAAT:G	donor_loss	0.9700
20:31368710:T:G	donor_loss	0.9700
20:31372856:GC:G	acceptor_gain	0.9700
20:31369169:A:AG	donor_gain	0.9600
20:31369178:C:CG	donor_gain	0.9600
20:31371306:G:T	donor_gain	0.9600
20:31372856:GCCT:G	acceptor_gain	0.9600
20:31370105:GG:G	donor_gain	0.9400
20:31370106:GG:G	donor_gain	0.9400
20:31372848:A:AG	acceptor_gain	0.9300
20:31371306:G:GT	donor_gain	0.9200
20:31368725:G:T	donor_gain	0.9100
20:31369204:T:G	donor_gain	0.9100
20:31372853:TCAGC:T	acceptor_gain	0.9100
20:31372854:CAG:C	acceptor_gain	0.9100
20:31369204:T:TG	donor_gain	0.9000
20:31372852:TTCAG:T	acceptor_gain	0.9000
20:31372853:TCA:T	acceptor_loss	0.9000
20:31372855:AGC:A	acceptor_loss	0.9000
20:31372855:A:T	acceptor_gain	0.8900
20:31372856:GCCTA:G	acceptor_gain	0.8900
20:31372856:G:C	acceptor_gain	0.8700
20:31372856:GCC:G	acceptor_gain	0.8500
20:31372849:T:G	acceptor_gain	0.8400

AlphaMissense

800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31372910:T:A	C38S	0.989
20:31372911:G:C	C38S	0.989
20:31372961:T:A	C55S	0.986
20:31372962:G:C	C55S	0.986
20:31372877:T:A	C27S	0.985
20:31372878:G:C	C27S	0.985
20:31372898:T:A	C34S	0.985
20:31372899:G:C	C34S	0.985
20:31372958:T:A	C54S	0.983
20:31372959:G:C	C54S	0.983
20:31372940:T:A	C48S	0.974
20:31372941:G:C	C48S	0.974
20:31372893:G:A	G32E	0.973
20:31372959:G:A	C54Y	0.973
20:31372962:G:A	C55Y	0.973
20:31372910:T:C	C38R	0.972
20:31372958:T:C	C54R	0.972
20:31372961:T:C	C55R	0.972
20:31372941:G:A	C48Y	0.971
20:31372960:C:G	C54W	0.971
20:31372877:T:C	C27R	0.969
20:31372963:C:G	C55W	0.967
20:31372899:G:A	C34Y	0.966
20:31372911:G:A	C38Y	0.965
20:31372903:G:C	R35S	0.963
20:31372903:G:T	R35S	0.963
20:31372959:G:T	C54F	0.962
20:31372942:C:G	C48W	0.961
20:31372911:G:T	C38F	0.960
20:31372962:G:T	C55F	0.960

dbSNP variants (sampled 300 via entrez): RS1000512055 (20:31373794 T>A), RS1000828890 (20:31374094 A>G), RS1000946528 (20:31374073 C>T), RS1001019272 (20:31367793 A>G), RS1001154415 (20:31367575 C>A,T), RS1001159530 (20:31367599 G>A), RS1001438614 (20:31367756 G>C), RS1003023050 (20:31370781 C>T), RS1003361641 (20:31372105 G>A), RS1003369371 (20:31372123 G>T), RS1003977606 (20:31367271 T>C), RS1004332886 (20:31367025 G>C), RS1005048606 (20:31373683 G>A,T), RS1005159533 (20:31373302 T>C), RS1005444631 (20:31370053 A>C,G)

Disease associations

OMIM: gene MIM:607650 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004639_6	Prudent dietary pattern	2.000000e-06
GCST010346_28	TPE interval (resting)	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004644	TPE interval measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Cadmium	decreases expression, increases abundance	1
Folic Acid	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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