AlphaFold version 4's predicted three-dimensional structure for the human KLHL36 protein.
Kelch-Like Protein 36 (abbreviated KLHL36) is a protein that in humans is encoded by the KLHL36gene.[6] The gene is a member of the Kelch-like gene family, which is characterized by a conserved BTB-BACK-Kelch domain architecture. Although the gene's specific function has yet to be characterized, it is predicted to serve as a substrate adaptor for Cullin-RING E3 ubiquitin ligase complexes, contributing to proteostasis.[7]
The KLHL 36 gene spans 19,176 base pairs on the positive strand of chromosome 16 (16q24.1).[6] KLHL36 sits in a genomic neighborhood with protein coding genes COTL1 upstream on the positive strand and USP10 downstream on the negative strand.[6]
There is no confirmed Mendelian disorder or single-gene disease associated with KLHL36. UniProt identifies 770 variants of the KLHL36 gene, with 94 marked as "pathogenic" or "likely pathogenic".[8] A single nucleotide polymorphism in KLHL36 has been reported as a risk variant for early onset Alzheimer's disease.[9]Genome-wide association studies (GWAS) have associated other polymorphisms with psychological resilience and stress-related psychiatric outcomes.[10]
Transcript
There are 6 known transcript variants of KLHL36, the canonical transcript variant being transcript variant 1. Transcript variant 1 encodes the longest and most common isoform, isoform 1.[6] Transcript variant 1 is 7,559 nucleotides in length and contains 5 exons.[6]
Analyses of KLHL36 expression have revealed that the protein is broadly expressed across all tissues, with particularly high levels of expression in the testis.[11] Transcriptomic analyses have revealed disease-associated changes in KLHL36 expression. KLHL36 mRNA levels have been shown to be lower in gastrointestinal tumors, and increased expression is correlated with positive prognoses in pancreatic cancer and cholangiocarcinoma.[12] Additionally, elevated KLHL36 levels have been associated with reduced tumor proliferation in pancreatic adenocarcinoma models, suggesting a possible tumor suppressor role.[13]
Protein
There are 3 protein isoforms of KLHL36, the canonical isoform being isoform 1, which is the longest and most common isoform.[6] Isoform 1 is a kelch-like protein that is 616 amino acids in size.[14] The protein contains a BTB/POZ domain of 135 amino acids at its N-terminus, which is predicted to mediate homodimerization and be involved in cullin 3 binding.[7][15] At its C-terminus, the protein contains 6 Kelch-motif domains which form a β-propeller that is predicted to be involved in substrate binding.[16][17]
Homology
The KLHL36 gene is highly conserved in vertebrates. Orthologs of KLHL36 are present in jawed vertebrates tracing back to cartilaginous fishes, although no ortholog has been identified in jawless vertebrates or invertebrates.[18] This suggests that the KLHL36 gene originated in a common ancestor of jawed vertebrates roughly 462 millions years ago.[19] KLHL is remarkably conserved across jawed vertebrates, sharing a greater than 77 percent sequence identity with many species of cartilaginous fishes, including Scyliorhinus canicula, Hypanus sabinus, and Callorhincus milii.[20]
54 paralogs of KLHL36 have been identified, with its closest relatives being KLHL13 and KLHL26.[8] The KLHL family of genes is a slightly smaller subset than the paralogs containing 42 genes, from KLHL1 to KLHL42.
1 2 Zhou Y, Zhang Q, Zhao Z, Hu X, You Q, Jiang Z (April 2024). "Targeting kelch-like (KLHL) proteins: achievements, challenges and perspectives". European Journal of Medicinal Chemistry. 269 116270. doi:10.1016/j.ejmech.2024.116270. PMID38490062.
↑ Maul S, Giegling I, Fabbri C, Corponi F, Serretti A, Rujescu D (March 2020). "Genetics of resilience: Implications from genome-wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 183 (2): 77–94. doi:10.1002/ajmg.b.32763. hdl:11585/793217. PMID31583809.
↑ Kumar S, Stecher G, Suleski M, Hedges SB (July 2017). "TimeTree: A Resource for Timelines, Timetrees, and Divergence Times". Molecular Biology and Evolution. 34 (7): 1812–1819. doi:10.1093/molbev/msx116. PMID28387841.
↑ "Protein BLAST". National Center for Biotechnology Information Protein BLAST. October 19, 2025. Retrieved October 19, 2025.
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