KLHL40

Chr 3AR

kelch like family member 40

Also known as: KBTBD5, NEM8, SRYP, SYRP

NCBI Gene: 131377 ENSG00000157119 UniProt: Q2TBA0 OMIM: 615340

The protein contains BACK, BTB/POZ, and Kelch repeat domains and localizes to the cytoplasm, though its exact cellular function remains unknown. Mutations cause nemaline myopathy with autosomal recessive inheritance. The predicted gain-of-function mechanism suggests that pathogenic variants likely alter normal protein function rather than cause loss of function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nemaline myopathy 8, autosomal recessiveMIM #615348

Nemaline myopathy 2, autosomal recessiveMIM #256030

Clinical highlights

Gene-disease validity (ClinGen)

nemaline myopathy 8 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

LOF

Mechanism· G2P