DEFA4

Chr 8

defensin alpha 4

Also known as: DEF4, HNP-4, HP-4, HP4

Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several alpha defensin genes are clustered on chromosome 8. This gene differs from other genes of this family by an extra 83-base segment that is apparently the result of a recent duplication within the coding region. The protein encoded by this gene, defensin, alpha 4, is found in the neutrophils; it exhibits corticostatic activity and inhibits corticotropin stimulated corticosterone production. [provided by RefSeq, Oct 2014]

0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.38
LOEUF
DN
Mechanism· predicted
Clinical SummaryDEFA4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.38LOEUF
pLI 0.498
Z-score 1.28
OE 0.00 (0.001.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.34Z-score
OE missense 1.84 (1.561.98)
112 obs / 60.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.001.38)
00.351.4
Missense OE1.84 (1.561.98)
00.61.4
Synonymous OE1.48
01.21.6
LoF obs/exp: 0 / 1.9Missense obs/exp: 112 / 60.8Syn Z: -1.76
DN
0.7229th %ile
GOF
0.4875th %ile
LOF
0.2680th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DEFA4 · 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