TABLE 2.
NDD-causing genes encoding CUL substrate receptors and associated syndromes.
| Gene | E3 Ubiquitin ligase | OMIM | Syndrome | References | Described regulator of: | References |
| CCNF | SKP1-CUL1-F-box | 619141 | FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 5 | Williams et al. (2016) | HIV infectivity in CD4 + T-cells | Augustine et al. (2017) |
| CRBN | DDB1-CUL4-X-box | 607417 | MENTAL RETARDATION, AUTOSOMAL RECESSIVE 2 | Higgins et al. (2004) | TLR signaling, T-cell function | Millrine et al. (2016); Min et al. (2016); Yang et al. (2018); Hesterberg et al. (2020) |
| DCAF8 | DDB1-CUL4-X-box | 610100 | GIANT AXONAL NEUROPATHY 2 | Klein et al. (2014) | Inflammatory cytokines | Peng et al. (2020) |
| ERCC8 | DDB1-CUL4-X-box | 216400 614621 | COCKAYNE SYNDROME A UV-SENSITIVE SYNDROME 2 | Nardo et al. (2009) | Inflammation | Ku and Cheng (2020) |
| FBXO7 | SKP1-CUL1-F-box | 260300 | PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE EARLY-ONSET | Shojaee et al. (2008) | NF-κB signaling | Kuiken et al. (2012) |
| FBXO11 | SKP1-CUL1-F-box | 618089 | INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND BEHAVIORAL ABNORMALITIES | Gregor et al. (2018) | Inflammation, TGF-β signaling | Hardisty-Hughes et al. (2006); Tateossian et al. (2009) |
| FBXO28 | SKP1-CUL1-F-box | DEVELOPMENTAL DELAY, DYSMORPHIC FEATURES, AND INTRACTABLE EPILEPSY | Balak et al. (2018) | Mitochondrial function | Zou et al. (2016) | |
| FBXO31 | SKP1-CUL1-F-box | 615979 | MENTAL RETARDATION, AUTOSOMAL RECESSIVE 45 | Mir et al. (2014) | Stem cell differentiation | Baek et al. (2021) |
| FBXO38 | SKP1-CUL1-F-box | 615575 | NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IID | Sumner et al. (2013) | T-cell function | Meng et al. (2018) |
| FBXW11 | SKP1-CUL1-F-box | 618914 | NEURODEVELOPMENTAL, JAW, EYE, AND DIGITAL SYNDROME | Holt et al. (2019) | Ig class switch recombination | Luo et al. (2019) |
| KCTD13 | BTB-CUL3-RBX1 | 611913; 614671 | CHROMOSOME 16p11.2 DELETION SYNDROME; CHROMOSOME 16p11.2 DUPLICATION SYNDROME | Crepel et al. (2011) | Cell motility | Chen et al. (2009) |
| KLHL7 | BTB-CUL3-RBX1 | 617055 | PERCHING SYNDROME | Friedman et al. (2009) | Nucleolar integrity | Kim et al. (2017) |
| KLHL15 | BTB-CUL3-RBX1 | 300982 | MENTAL RETARDATION, X-LINKED 103 | Mignon-Ravix et al. (2014) | DNA end resection | Ferretti et al. (2016) |
| RHOBTB2 | BTB-CUL3-RBX1 | 618004 | DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 64 | Straub et al. (2018) | Vesicle trafficking | Ji and Rivero (2016) |
The potential implication of the gene products in the regulation of innate and/or adaptive is indicated. When available, the OMIM (Online Mendelian Inheritance in Man®) disorder number is also reported.