DEFB121

Summary

DEFB121 (defensin beta 121, HGNC:18101) is a protein-coding gene on chromosome 20q11.21, encoding Beta-defensin 121 (Q5J5C9). Has antibacterial activity.

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. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 245934 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_001011878

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18101
Approved symbol	DEFB121
Name	defensin beta 121
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	DEFB-21
Ensembl gene	ENSG00000204548
Ensembl biotype	protein_coding
OMIM	616075
Entrez	245934

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000376312, ENST00000376314

RefSeq mRNA: 2 — MANE Select: NM_001011878 NM_001011878, NM_001171832

CCDS: CCDS33456

Canonical transcript exons

ENST00000376314 — 2 exons

Exon	Start	End
ENSE00001470143	31404845	31405085
ENSE00001470144	31406095	31406215

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 85.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1930 / max 351.2239, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186822	0.1930	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	85.35	gold quality
right testis	UBERON:0004534	71.89	gold quality
left testis	UBERON:0004533	71.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.85	gold quality
testis	UBERON:0000473	69.79	gold quality
sperm	CL:0000019	65.19	gold quality
pancreatic ductal cell	CL:0002079	59.51	silver quality
epithelial cell of pancreas	CL:0000083	54.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	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
endothelial cell	CL:0000115	53.20	gold quality
myocardium	UBERON:0002349	50.25	gold quality
tibialis anterior	UBERON:0001385	47.50	silver quality
deltoid	UBERON:0001476	47.48	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
ileal mucosa	UBERON:0000331	46.51	silver quality
quadriceps femoris	UBERON:0001377	46.43	gold quality
granulocyte	CL:0000094	45.61	silver quality
vastus lateralis	UBERON:0001379	45.40	gold quality
adult organism	UBERON:0007023	44.86	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
middle temporal gyrus	UBERON:0002771	43.32	gold quality
lower lobe of lung	UBERON:0008949	43.24	silver quality
secondary oocyte	CL:0000655	42.57	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
inferior vagus X ganglion	UBERON:0005363	41.30	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• This gene is thought to encode a peptide that displays antimicrobial activity. (PMID:15772680)

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), DEFB104B (ENSG00000177023), DEFB125 (ENSG00000178591), DEFB124 (ENSG00000180383), DEFB123 (ENSG00000180424), DEFB119 (ENSG00000180483), DEFB108B (ENSG00000184276), DEFB128 (ENSG00000185982), DEFB131A (ENSG00000186146), DEFB132 (ENSG00000186458), DEFB134 (ENSG00000205882), DEFB135 (ENSG00000205883), DEFB108C (ENSG00000215371), DEFB116 (ENSG00000215545), DEFB115 (ENSG00000215547), DEFB131B (ENSG00000225805)

Protein

Protein identifiers

Beta-defensin 121 — Q5J5C9 (reviewed: Q5J5C9)

Alternative names: Beta-defensin 21, Defensin, beta 121

All UniProt accessions (2): Q5J5C9, A0A384MDM0

UniProt curated annotations — full annotation on UniProt →

Function. Has antibacterial activity.

Subcellular location. Secreted.

Tissue specificity. Abundant expression in the male reproductive tract only.

Similarity. Belongs to the beta-defensin family.

RefSeq proteins (1): NP_001011878* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025933	Beta_defensin_dom	Domain
IPR050544	Beta-defensin	Family

Pfam: PF13841

UniProt features (5 total): disulfide bond 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5J5C9-F1	85.01	0.51

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): 23–50, 30–44, 34–51

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): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, 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, 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, GSE21063_WT_VS_NFATC1_KO_16H_ANTI_IGM_STIM_BCELL_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 (1): 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
immune response	1
defense response to symbiont	1
defense response to bacterium	1
response to stress	1
defense response	1
response to bacterium	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEFB121	DEFB113	Q30KQ7	626
DEFB121	DEFB115	Q30KQ5	621
DEFB121	DEFB129	Q9H1M3	620
DEFB121	DEFB135	Q30KP9	571
DEFB121	DEFB108B	Q8NET1	570
DEFB121	DEFB126	Q9BYW3	543
DEFB121	DEFB131A	P59861	530
DEFB121	DEFB116	Q30KQ4	507
DEFB121	UNC5CL	Q8IV45	471
DEFB121	A0A0G2JN59	A0A0G2JN59	468
DEFB121	DEFB110	Q30KQ9	465
DEFB121	DEFB112	Q30KQ8	434
DEFB121	WFDC10A	Q9H1F0	431
DEFB121	CCDC63	Q8NA47	371
DEFB121	LRFN2	Q9ULH4	370

IntAct

33 interactions, top by confidence:

A	B	Type	Score
DEFB121	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	DEFB121	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	CLEC2D	psi-mi:“MI:0915”(physical association)	0.560
CD40	DEFB121	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	IL27RA	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	LAYN	psi-mi:“MI:0915”(physical association)	0.560
GJA8	DEFB121	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	NECTIN4	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	COL6A2	psi-mi:“MI:0914”(association)	0.530
DEFB121	CLEC2D	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	LRRC25	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	IL27RA	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	SSMEM1	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	LAYN	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	GJA8	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	CD40	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	FAM209A	psi-mi:“MI:0915”(physical association)	0.000
DEFB121	NECTIN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): DEFB121 (Two-hybrid), TCTEX1D2 (Affinity Capture-MS), VWDE (Affinity Capture-MS), CPS1 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), OS9 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), DEFB121 (Affinity Capture-MS), DEFB121 (Two-hybrid), DEFB121 (Two-hybrid), DEFB121 (Two-hybrid), DEFB121 (Two-hybrid), DEFB121 (Two-hybrid)

ESM2 similar proteins: A4H202, A4H203, A4H204, A4H206, A4H209, A4H211, A4H212, A4H213, A4H225, A4H227, A8MXU0, O19039, O89117, P0C8A5, P0C8A6, P0C8A7, Q30KJ3, Q30KK4, Q30KK6, Q30KL6, Q30KN8, Q30KP6, Q30KP8, Q32P86, Q32ZF3, Q32ZG3, Q32ZG7, Q32ZH5, Q32ZH6, Q32ZH9, Q32ZI2, Q4QY38, Q5IAB3, Q5IAB9, Q5J5C9, Q5J5Z9, Q5J600, Q5J602, Q6GXJ1, Q6IV23

Diamond homologs: A4H220, A4H221, A4H222, A4H223, P0C8A5, Q30KK6, Q30KK9, Q30KQ5, Q5J5C9, Q95LI0, Q96PH6, A4H225, A4H226, A4H227, A4H228, Q30KK8, Q30KL1, Q30KQ4, Q30KT5, Q32P86, Q5J600, Q5J602, Q8K3I8, Q8N690, Q9BEE3, A4H235, A4H236, Q30KK5, Q5J5D0, Q5J5Z9, Q8K3U4, Q8N688, A4H238, A4H239, A4H240, A4H241, Q30KK3, Q30KK4, Q32ZG7, Q8N687

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	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

82 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31405086:C:CC	acceptor_gain	0.9800
20:31405081:CATGA:C	acceptor_gain	0.9700
20:31405083:TGA:T	acceptor_gain	0.9700
20:31406090:TTTA:T	donor_loss	0.9700
20:31406093:ACCTG:A	donor_loss	0.9700
20:31406094:CCTGG:C	donor_loss	0.9700
20:31406191:A:C	donor_gain	0.9600
20:31405084:GA:G	acceptor_gain	0.9500
20:31405093:C:CT	acceptor_gain	0.9400
20:31405082:ATGA:A	acceptor_gain	0.9100
20:31405084:GAC:G	acceptor_loss	0.9000
20:31405086:CT:C	acceptor_loss	0.9000
20:31405094:A:T	acceptor_gain	0.8700
20:31406149:T:TA	donor_gain	0.8500
20:31406102:G:T	donor_gain	0.7700
20:31406067:C:CA	donor_gain	0.7500
20:31406085:T:TA	donor_gain	0.7000
20:31405534:TAGGG:T	donor_gain	0.6900
20:31405552:C:CA	donor_gain	0.6700
20:31405810:TCCA:T	donor_gain	0.6500
20:31406016:A:AT	donor_gain	0.6400
20:31406100:G:C	donor_gain	0.6200
20:31406093:A:AC	donor_gain	0.6000
20:31406094:C:CC	donor_gain	0.6000
20:31405513:A:AC	donor_gain	0.5700
20:31405970:C:CT	donor_gain	0.5600
20:31405971:T:TT	donor_gain	0.5600
20:31405811:CCAT:C	donor_gain	0.5500
20:31406101:TG:T	donor_gain	0.5500
20:31406013:C:CA	donor_gain	0.5300

AlphaMissense

476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31404995:C:G	C50S	0.983
20:31404996:A:T	C50S	0.983
20:31405062:C:A	G28C	0.981
20:31405072:C:A	W24C	0.980
20:31405072:C:G	W24C	0.980
20:31405076:C:G	C23S	0.975
20:31405077:A:T	C23S	0.975
20:31404996:A:G	C50R	0.974
20:31405055:C:G	C30S	0.974
20:31405056:A:T	C30S	0.974
20:31404992:C:G	C51S	0.973
20:31404993:A:T	C51S	0.973
20:31405013:C:G	C44S	0.967
20:31405014:A:T	C44S	0.967
20:31405077:A:G	C23R	0.967
20:31405043:C:G	C34S	0.965
20:31405044:A:T	C34S	0.965
20:31405061:C:T	G28D	0.965
20:31404993:A:G	C51R	0.961
20:31404994:G:C	C50W	0.957
20:31405043:C:T	C34Y	0.956
20:31405056:A:G	C30R	0.956
20:31404992:C:T	C51Y	0.955
20:31405014:A:G	C44R	0.953
20:31405044:A:G	C34R	0.952
20:31405013:C:T	C44Y	0.949
20:31405075:A:C	C23W	0.947
20:31404995:C:T	C50Y	0.941
20:31404995:C:A	C50F	0.940
20:31405055:C:T	C30Y	0.939

dbSNP variants (sampled 300 via entrez): RS1000213770 (20:31412781 T>C), RS1000389393 (20:31418302 A>G), RS1000548691 (20:31414599 C>T), RS1001007928 (20:31406898 C>T), RS1001033506 (20:31407743 T>C), RS1001035769 (20:31408142 T>C), RS1001122037 (20:31407132 C>A,T), RS1001172209 (20:31414973 G>A,C), RS1001339725 (20:31408308 C>G,T), RS1001376864 (20:31409370 T>TA), RS1001764351 (20:31409065 G>A), RS1002165331 (20:31415461 G>A), RS1002951311 (20:31416431 G>A), RS1003008738 (20:31410606 A>G,T), RS1003127823 (20:31409978 G>A)

Disease associations

OMIM: gene MIM:616075 | 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
GCST90013406_38	Liver enzyme levels (alkaline phosphatase)	8.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004533	alkaline phosphatase 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
Benzo(a)pyrene	affects methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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