DEFA6

Chr 8

defensin alpha 6

Also known as: DEF6, HD-6

NCBI Gene: 1671ENSG00000164822UniProt: Q01524

The protein is an antimicrobial peptide highly expressed in Paneth cells of the small intestine that forms fibril-like structures to entangle bacteria and fungi, preventing microbial invasion across the intestinal epithelial barrier. Currently, no Mendelian diseases have been definitively associated with DEFA6 mutations in humans. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF ~2.0), suggesting it may be tolerant to complete loss of function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
103
P/LP submissions
0%
P/LP missense
1.97
LOEUF
DN
Mechanism· predicted
Clinical Summary— DEFA6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
102 unique Pathogenic / Likely Pathogenic· 32 VUS of 141 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
1.97LOEUF
pLI 0.000
Z-score -2.41
OE 2.77 (1.01–1.97)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.86Z-score
OE missense 1.73 (1.45–1.95)
89 obs / 51.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE2.77 (1.01–1.97)
0≤0.351.4
Missense OE1.73 (1.45–1.95)
0≤0.61.4
Synonymous OE1.87
0≤1.21.6
LoF obs/exp: 6 / 2.2Missense obs/exp: 89 / 51.5Syn Z: -3.08
DN
0.83top 10%
GOF
0.4480th %ile
LOF
0.1895th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic98
Likely Pathogenic4
VUS32
Likely Benign1
Benign4
98
Pathogenic
4
Likely Pathogenic
32
VUS
1
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
98
0
98
Likely Pathogenic
0
0
4
0
4
VUS
0
21
11
0
32
Likely Benign
0
1
0
0
1
Benign
0
1
3
0
4
Total0231160139

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

View in ClinVar →

Protein Context — Lollipop Plot

DEFA6 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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