KLHL23

Chr 2

kelch like family member 23

Also known as: DITHP

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in membrane. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.65
Clinical SummaryKLHL23
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?
0.65LOEUF
pLI 0.004
Z-score 2.79
OE 0.36 (0.210.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.73Z-score
OE missense 0.88 (0.800.97)
262 obs / 297.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.36 (0.210.65)
00.351.4
Missense OE?0.88 (0.800.97)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 8 / 22.2Missense obs/exp: 262 / 297.6Syn Z: 0.14

This gene — mechanism propensity

DN
0.6649th %ile
GOF
0.6638th %ile
LOF
0.2678th %ile

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

GOFprediction above median
DNprediction 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

KLHL23 · 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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