DEFB131A

Chr 4

defensin beta 131A

Also known as: DEFB-31, DEFB131

NCBI Gene: 644414ENSG00000186146UniProt: P59861

The protein encoded by this gene is a secreted antimicrobial beta defensin that has antibacterial activity and promotes cytokine and chemokine production in response to bacterial stimulation. No Mendelian diseases have been definitively associated with mutations in DEFB131A. The gene shows minimal constraint against loss-of-function variants, suggesting that complete loss of function may be tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
66
P/LP submissions
0%
P/LP missense
1.94
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DEFB131A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 unique Pathogenic / Likely Pathogenic· 26 VUS of 95 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.94LOEUF
pLI 0.013
Z-score -0.94
OE 2.01 (0.52–1.94)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.49Z-score
OE missense 2.25 (1.68–1.99)
71 obs / 31.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE2.01 (0.52–1.94)
0≤0.351.4
Missense OE2.25 (1.68–1.99)
0≤0.61.4
Synonymous OE2.50
0≤1.21.6
LoF obs/exp: 2 / 1.0Missense obs/exp: 71 / 31.6Syn Z: -3.87
DN
0.95top 5%
GOF
0.7029th %ile
LOF
0.03100th %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

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic2
VUS26
Likely Benign3
64
Pathogenic
2
Likely Pathogenic
26
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
64
0
64
Likely Pathogenic
0
0
2
0
2
VUS
0
20
6
0
26
Likely Benign
0
1
2
0
3
Benign
0
0
0
0
0
Total02174095

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DEFB131A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients