KLHDC7B

Chr 22

kelch domain containing 7B

NCBI Gene: 113730 ENSG00000130487 UniProt: Q96G42 OMIM: 620521

The protein functions as a Kelch domain-containing protein involved in cellular processes, though its specific molecular function remains poorly characterized. Mutations cause a neurodevelopmental disorder with intellectual disability, seizures, and brain abnormalities, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.51

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.000

Z-score 0.11

OE 0.97 (0.64–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.19Z-score

OE missense 0.83 (0.75–0.91)

307 obs / 371.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.97 (0.64–1.51)

0≤0.351.4

Missense OE?0.83 (0.75–0.91)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 14 / 14.5Missense obs/exp: 307 / 371.3Syn Z: 0.78

Background carrier burden — how many people carry a rare variant somewhere in KLHDC7B?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 28

1,415 rare PASS variants

Rare truncating (LoF)

1 in 160

247 rare PASS variants

Rare synonymous (reference)

1 in 57

668 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KLHDC7B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

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