DEFB108B

Chr 11

defensin beta 108B

Also known as: DEFB-8, hBD-8

NCBI Gene: 245911 ENSG00000184276 UniProt: Q8NET1

DEFB108B encodes a beta-defensin antimicrobial peptide with antibacterial activity that is part of the innate immune system. This gene shows very low constraint against loss-of-function variants (pLI = 0.002, LOEUF = 1.96), and no Mendelian diseases have been established for mutations in this gene. The clinical significance of DEFB108B variants in pediatric patients remains unclear.

ResearchSummary from RefSeq, UniProt

Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. A pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Oct 2014]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.96

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.96LOEUF

pLI 0.002

Z-score -1.86

OE 3.01 (0.74–1.96)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.09Z-score

OE missense 1.49 (1.21–1.84)

57 obs / 38.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?3.01 (0.74–1.96)

0≤0.351.4

Missense OE?1.49 (1.21–1.84)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 1.0Missense obs/exp: 57 / 38.1Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in DEFB108B?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

111 rare PASS variants

Rare truncating (LoF)

1 in 520

18 rare PASS variants

Rare synonymous (reference)

1 in 3,400

26 rare PASS variants

Rare missense and truncating variants are carried at similar rates in DEFB108B; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 320	1 in 840
South Asian	~43k	1 in 140	1 in 5,300
Remaining (unassigned)	~30k	1 in 640	1 in 450
European (Finnish)	~27k	1 in 610	1 in 5,300
Admixed American	~22k	1 in 700	1 in 1,800
African / African American	~21k	1 in 330	1 in 420
East Asian	~20k	1 in 220	1 in 680
Ashkenazi Jewish	~13k	≈ 1 in 3,200	1 in 690
Middle Eastern	~2,067	1 in 340	≈ 1 in 2,100

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓