DEFB121

Chr 20

defensin beta 121

Also known as: DEFB21, ESC42RELC

This gene encodes a beta-defensin, an antimicrobial peptide that has antibacterial activity and protects tissues from microbial infections. The gene shows low constraint to loss-of-function variation (pLI 0.10, LOEUF 1.88), and no established Mendelian diseases have been associated with DEFB121 mutations. Current evidence does not support a role for this gene in pediatric neurogenetic disorders.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.88
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryDEFB121
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.88LOEUF
pLI 0.097
Z-score 0.09
OE 0.90 (0.251.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.06Z-score
OE missense 1.03 (0.791.35)
38 obs / 36.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.90 (0.251.88)
00.351.4
Missense OE1.03 (0.791.35)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 1 / 1.1Missense obs/exp: 38 / 36.9Syn Z: -0.51
DN
0.74top 25%
GOF
0.6443th %ile
LOF
0.1399th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DEFB121 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found