KBTBD11

Chr 8

kelch repeat and BTB domain containing 11

Also known as: KLHDC7C

NCBI Gene: 9920 ENSG00000176595 UniProt: O94819 OMIM: 618794

The protein functions as a substrate adaptor for the CRL3 ubiquitin ligase complex, targeting specific proteins for degradation. Mutations cause autosomal recessive intellectual disability with seizures and skeletal abnormalities. The gene shows tolerance to loss-of-function variants in the general population (pLI 0.06, LOEUF 1.0), suggesting the recessive inheritance pattern aligns with population constraint data.

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.062

Z-score 1.57

OE 0.39 (0.18–1.00)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.51Z-score

OE missense 0.90 (0.79–1.02)

171 obs / 190.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.18–1.00)

0≤0.351.4

Missense OE?0.90 (0.79–1.02)

0≤0.61.4

Synonymous OE?1.34

0≤1.21.6

LoF obs/exp: 3 / 7.7Missense obs/exp: 171 / 190.7Syn Z: -2.60

Background carrier burden — how many people carry a rare variant somewhere in KBTBD11?

gnomAD v4 · ~717k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 49

1,501 rare PASS variants

Rare truncating (LoF)

1 in 830

143 rare PASS variants

Rare synonymous (reference)

1 in 48

787 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KBTBD11. 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)	~553k	1 in 58	1 in 950
South Asian	~42k	1 in 39	1 in 510
Remaining (unassigned)	~30k	1 in 41	1 in 680
Admixed American	~22k	1 in 45	1 in 630
African / African American	~21k	1 in 44	1 in 630
East Asian	~19k	1 in 86	1 in 760
European (Finnish)	~19k	1 in 170	1 in 960
Ashkenazi Jewish	~13k	1 in 140	1 in 750
Middle Eastern	~2,836	1 in 47	≈ 1 in 1,000

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