KBTBD3

Chr 11

kelch repeat and BTB domain containing 3

Also known as: BKLHD3

NCBI Gene: 143879 ENSG00000182359 UniProt: Q8NAB2

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.88

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?

0.88LOEUF

pLI 0.000

Z-score 2.01

OE 0.54 (0.34–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.87 (0.78–0.96)

269 obs / 310.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.34–0.88)

0≤0.351.4

Missense OE?0.87 (0.78–0.96)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 12 / 22.2Missense obs/exp: 269 / 310.8Syn Z: 0.29

Background carrier burden — how many people carry a rare variant somewhere in KBTBD3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

711 rare PASS variants

Rare truncating (LoF)

1 in 1,400

105 rare PASS variants

Rare synonymous (reference)

1 in 150

248 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KBTBD3. 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 140	1 in 1,500
South Asian	~43k	1 in 88	1 in 940
Remaining (unassigned)	~30k	1 in 92	1 in 2,000
European (Finnish)	~27k	1 in 160	1 in 1,800
Admixed American	~22k	1 in 63	1 in 1,100
African / African American	~21k	1 in 120	1 in 2,100
East Asian	~20k	1 in 140	1 in 610
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 120	none seen

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 3 marginal. Genomes: all 2.? see exons ↓