DEFB121

Chr 20

defensin beta 121

Also known as: DEFB21, ESC42RELC

NCBI Gene: 245934 ENSG00000204548 UniProt: Q5J5C9

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.097

Z-score 0.09

OE 0.90 (0.25–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.03 (0.79–1.35)

38 obs / 36.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.90 (0.25–1.88)

0≤0.351.4

Missense OE?1.03 (0.79–1.35)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 1 / 1.1Missense obs/exp: 38 / 36.9Syn Z: -0.51

Background carrier burden — how many people carry a rare variant somewhere in DEFB121?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,200

91 rare PASS variants

Rare truncating (LoF)

1 in 2,700

17 rare PASS variants

Rare synonymous (reference)

1 in 910

40 rare PASS variants

Rare missense and truncating variants are carried at similar rates in DEFB121; 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 1,400	1 in 2,600
South Asian	~43k	1 in 610	1 in 7,200
Remaining (unassigned)	~30k	1 in 1,800	1 in 3,400
European (Finnish)	~27k	≈ 1 in 27,000	none seen
Admixed American	~22k	1 in 2,800	1 in 4,500
African / African American	~21k	1 in 380	≈ 1 in 6,300
East Asian	~20k	1 in 580	1 in 2,800
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 360	1 in 480

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓