KBTBD13

Chr 15

kelch repeat and BTB domain containing 13

Also known as: HCG1645727, NEM6

NCBI Gene: 390594 ENSG00000234438 UniProt: C9JR72

KBTBD13 encodes a protein containing BTB and kelch repeat domains that localizes to the cytoplasm, though its exact cellular function remains unknown. Mutations cause nemaline myopathy 6 through an autosomal dominant inheritance pattern with a gain-of-function mechanism. The protein belongs to a family involved in diverse cellular processes including transcription regulation, protein degradation, and cytoskeleton regulation.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The gene belongs to a family of genes encoding proteins containing a BTB domain and several kelch repeats. The BTB domain functions as a protein-protein interaction module, which includes an ability to self-associate or to interact with non-BTB domain-containing proteins. The kelch motif typically occurs in groups of five to seven repeats, and has been found in proteins with diverse functions. Known functions of these family members include transcription regulation, ion channel tetramerization and gating, protein ubiquitination or degradation, and cytoskeleton regulation. The exact function of this family member has yet to be determined. [provided by RefSeq, Jun 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNemaline myopathy 6

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nemaline myopathy 6 · AD · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.87

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?

1.87LOEUF

pLI 0.000

Z-score -0.91

OE 1.31 (0.84–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.59Z-score

OE missense 1.10 (1.00–1.21)

307 obs / 279.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.31 (0.84–1.87)

0≤0.351.4

Missense OE?1.10 (1.00–1.21)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 13 / 9.9Missense obs/exp: 307 / 279.4Syn Z: -1.44

Background carrier burden — how many people carry a rare variant somewhere in KBTBD13?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

960 rare PASS variants

Rare truncating (LoF)

1 in 510

142 rare PASS variants

Rare synonymous (reference)

1 in 110

454 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KBTBD13. 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 81	1 in 530
South Asian	~43k	1 in 67	1 in 280
Remaining (unassigned)	~30k	1 in 50	1 in 540
European (Finnish)	~26k	1 in 110	1 in 2,500
Admixed American	~22k	1 in 56	1 in 740
African / African American	~21k	1 in 51	1 in 420
East Asian	~20k	1 in 53	1 in 550
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 5,800
Middle Eastern	~2,884	1 in 53	≈ 1 in 630

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