KLHL41

Chr 2AR

kelch like family member 41

Also known as: KBTBD10, Krp1, SARCOSIN

This gene is a member of the kelch-like family. The encoded protein contains a BACK domain, a BTB/POZ domain, and 5 Kelch repeats. This protein is thought to function in skeletal muscle development and maintenance. Mutations in this gene have been associated with nemaline myopathy (NM), a rare congenital muscle disorder. [provided by RefSeq, Mar 2015]

OMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 0.801 OMIM phenotype
Clinical SummaryKLHL41
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Gene-Disease Validity (ClinGen)
nemaline myopathy 9 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.80LOEUF
pLI 0.000
Z-score 2.27
OE 0.47 (0.290.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.89Z-score
OE missense 0.86 (0.780.95)
282 obs / 327.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.47 (0.290.80)
00.351.4
Missense OE?0.86 (0.780.95)
00.61.4
Synonymous OE?0.86
01.21.6
LoF obs/exp: 10 / 21.3Missense obs/exp: 282 / 327.1Syn Z: 1.17

This gene — mechanism propensity

DN
0.75top 25%
GOF
0.72top 25%
LOF
0.2580th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KLHL41 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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