The protein functions as a substrate-specific adapter in a cullin 3-based E3 ubiquitin ligase complex that regulates mitotic progression and cytokinesis by controlling aurora B kinase localization and activity during cell division. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and neurological abnormalities. This gene is highly constrained against loss-of-function variants (pLI = 0.82, LOEUF = 0.41), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.41
Clinical SummaryKLHL9
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
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ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 85 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.820
Z-score 3.38
OE 0.16 (0.070.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.87Z-score
OE missense 0.71 (0.640.79)
231 obs / 325.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.070.41)
00.351.4
Missense OE0.71 (0.640.79)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 3 / 18.8Missense obs/exp: 231 / 325.9Syn Z: -1.81

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic2
VUS85
Likely Benign10
3
Pathogenic
2
Likely Pathogenic
85
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
2
0
2
VUS
2
67
3
13
85
Likely Benign
0
0
0
10
10
Benign
0
0
0
0
0
Total267823100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KLHL9 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗