KLHL3

Chr 5q31.2

kelch like family member 3

Aliases:: KIAA1129
MANE:: ENST00000309755.9

OMIM: 605775 ↗NCBI: 26249 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

KLHL3 · Q9UH77

v62025-08-01

Predicted Aligned Error matrix for KLHL3 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

90.5/ 100

Very high

587 residues

Confidence breakdown

Very high(≥ 90)71%
Confident(70–90)23%
Low(50–70)1%
Very low(< 50)4%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Extreme early-onset hypertension
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Disease associations (Open Targets)

pseudohypoaldosteronism type 2D
0.83
pseudohypoaldosteronism type 2A
0.56
atrial fibrillation
0.39
pseudohypoaldosteronism type 2
0.38
neurodegenerative disease
0.37
hereditary disease
0.34
prostatitis
0.28
benign neoplasm of adrenal gland
0.27
essential hypertension
0.27
cerebral palsy
0.27

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Kelch-like protein 3

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:25313067, PubMed:35093948). The BCR(KLHL3) complex acts by mediating ubiquitination and degradation of WNK1 and WNK4, two activators of Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney, thereby regulating NaCl reabsorption (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:25313067, PubMed:35093948). The BCR(KLHL3) complex also mediates ubiquitination and degradation of WNK3 (PubMed:35179207). The BCR(KLHL3) complex also mediates ubiquitination of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney, leading to its degradation (By similarity)