KLHL2

Chr 4

kelch like family member 2

Also known as: ABP-KELCH, MAV, MAYVEN

KLHL2 encodes a substrate-specific adapter protein for E3 ubiquitin ligase complexes that targets specific proteins including WNK kinases for proteasomal degradation and promotes actin cytoskeleton reorganization and oligodendrocyte precursor cell projection growth. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
45
P/LP submissions
0%
P/LP missense
0.18
LOEUF· LoF intol.
Mechanism
Clinical SummaryKLHL2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 40 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 5.09
OE 0.06 (0.020.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.89Z-score
OE missense 0.40 (0.350.46)
134 obs / 333.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.020.18)
00.351.4
Missense OE0.40 (0.350.46)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 2 / 34.0Missense obs/exp: 134 / 333.8Syn Z: 0.77

ClinVar Variant Classifications

108 submitted variants in ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic2
VUS40
Likely Benign7
Benign1
43
Pathogenic
2
Likely Pathogenic
40
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
2
0
2
VUS
0
33
7
0
40
Likely Benign
0
2
0
5
7
Benign
0
0
1
0
1
Total03553593

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

View in ClinVar →

Protein Context — Lollipop Plot

KLHL2 · 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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Clinical Literature
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