KBTBD12

Chr 3

kelch repeat and BTB domain containing 12

Also known as: KLHDC6

NCBI Gene: 166348 ENSG00000187715 UniProt: Q3ZCT8

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. 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

1.23

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?

1.23LOEUF

pLI 0.000

Z-score 0.62

OE 0.87 (0.63–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.28Z-score

OE missense 0.96 (0.87–1.05)

316 obs / 330.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.63–1.23)

0≤0.351.4

Missense OE?0.96 (0.87–1.05)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 23 / 26.4Missense obs/exp: 316 / 330.2Syn Z: 1.01

Background carrier burden — how many people carry a rare variant somewhere in KBTBD12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

756 rare PASS variants

Rare truncating (LoF)

1 in 570

116 rare PASS variants

Rare synonymous (reference)

1 in 360

246 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KBTBD12. 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 83	1 in 760
South Asian	~43k	1 in 63	1 in 390
Remaining (unassigned)	~30k	1 in 71	1 in 360
European (Finnish)	~27k	1 in 250	1 in 1,400
Admixed American	~22k	1 in 62	1 in 320
African / African American	~21k	1 in 78	1 in 940
East Asian	~20k	1 in 140	1 in 230
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 120	1 in 410

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓