TABLE 1.
NDD-causing genes encoding E3 ubiquitin ligases and associated syndromes.
| Gene | OMIM | Syndrome | References | Described regulator of: | References |
| CUL3 | 619239 | NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT AUTISM OR SEIZURES | Nakashima et al. (2020) | T-cell function | Mathew et al. (2012) |
| CUL4B | 300354 | MENTAL RETARDATION, X-LINKED, SYNDROMIC, CABEZAS TYPE | Tarpey et al. (2007) | NF-κB signaling | Hung et al. (2014); Song et al. (2021) |
| CUL7 | 273750 | THREE M SYNDROME 1 | Huber et al. (2005) | Ig class switch recombination | Luo et al. (2019) |
| HACE1 | 616756 | SPASTIC PARAPLEGIA AND PSYCHOMOTOR RETARDATION WITH OR WITHOUT SEIZURES | Hollstein et al. (2015) | Antiviral immunity | Mao et al. (2016) |
| HERC1 | 617011 | MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION | Nguyen et al. (2016) | MAP kinase and mTOR signaling | Sala-Gaston et al. (2020) |
| HERC2 | 615516 | MENTAL RETARDATION, AUTOSOMAL RECESSIVE 38 | Morice-Picard et al. (2016) | Genomic stability | Sala-Gaston et al. (2020) |
| HECW2 | 617268 | NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, SEIZURES, AND ABSENT LANGUAGE | Berko et al. (2017) | Mitotic metaphase/anaphase transition, heterochromatin packaging | Lu et al. (2013); Krishnamoorthy et al. (2018) |
| HUWE1 | 309590 | MENTAL RETARDATION, X-LINKED, SYNDROMIC, TURNER TYPE | Froyen et al. (2008) | Inflammasome, NF-κB signaling | Guo et al. (2020b); Ohtake et al. (2016) |
| IRF2BPL | 618088 | NEURODEVELOPMENTAL DISORDER WITH REGRESSION, ABNORMAL MOVEMENTS, LOSS OF SPEECH, AND SEIZURES | Tran Mau-Them et al. (2019) | Apoptosis, survival, and cell differentiation | Ramalho-Oliveira et al. (2019) |
| ITCH | 613385 | AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM | Lohr et al. (2010) | Inflammation, T-cell differentiation | Field et al. (2020) |
| LRSAM1 | 614436 | CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2P | Guernsey et al. (2010) | Antibacterial autophagic response | Ng et al. (2011) |
| MAGEL2 | 615547 | SCHAAF-YANG SYNDROME | Ates et al. (2019) | Immune infiltration | Arora et al. (2020) |
| MID1 | 300000 | OPITZ GBBB SYNDROME | Quaderi et al. (1997) | T-cell differentiation, Antiviral immunity | Collison et al. (2013); Chen et al. (2021) |
| MID2 | 300928 | MENTAL RETARDATION, X-LINKED 101 | Geetha et al. (2014) | Cytokinesis | Zanchetta and Meroni (2019) |
| NEDD4L | 617201 | PERIVENTRICULAR NODULAR HETEROTOPIA 7 | Broix et al. (2016) | Antiviral immunity | Gao et al. (2021) |
| NHLRC1 | 254780 | EPILEPSY, PROGRESSIVE MYOCLONIC, 2B, INCLUDED | Chan et al. (2003) | Inflammatory cytokines | Lopez-Gonzalez et al. (2017) |
| PRKN | 600116 | PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE | Kitada et al. (1998) | Antiviral immunity | Sliter et al. (2018) |
| RLIM | 300978 | TONNE-KALSCHEUER SYNDROME | Tonne et al. (2015) | Imprinted X chromosome inactivation | Gontan et al. (2018) |
| RNF125 | 616260 | TENORIO SYNDROME | Tenorio et al. (2014) | Antiviral immunity, inflammasome IL-36 signaling | Oshiumi et al. (2010); Jia et al. (2017); Saha et al. (2018); Tang et al. (2020) |
| RNF168 | 611943 | RIDDLE SYNDROME | Stewart et al. (2009) | Ig class switch recombination, Immune deficiency | Ramachandran et al. (2010); Chinn et al. (2017) |
| RNF170 | 608984 | ATAXIA, SENSORY, 1, AUTOSOMAL DOMINANT | Valdmanis et al. (2011) | Antiviral immunity | Song et al. (2020) |
| RNF216 | 212840 | GORDON HOLMES SYNDROME | Margolin et al. (2013) | TLR signaling, Antiviral immunity | Nakhaei et al. (2009); Kumazoe et al. (2017) |
| STUB1 | 615768; 618093 | SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 16; SPINOCEREBELLAR ATAXIA 48 | Shi et al. (2013); Genis et al. (2018) | TLR signaling, T-cell function, antiviral immunity, IL-4 signaling | Yang et al. (2011); Chen et al. (2013); Wei et al. (2014); Zhao et al. (2016); Zhou et al. (2018) |
| TRAF7 | 618164 | CARDIAC, FACIAL, AND DIGITAL ANOMALIES WITH DEVELOPMENTAL DELAY | Tokita et al. (2018) | NF-κB signaling | Zotti et al. (2011) |
| TRIM2 | 615490 | CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2R | Ylikallio et al. (2013) | New World arenavirus entry | Sarute et al. (2019) |
| TRIM36 | 206500 | ANENCEPHALY | Singh et al. (2017) | Cell cycle progression | Miyajima et al. (2009) |
| TRIM37 | 253250 | MULIBREY NANISM | Kallijarvi et al. (2002) | NF-κB signaling, Inflammation | Li et al. (2018); Zhao et al. (2021) |
| TRIM50 | 194050 | WILLIAMS-BEUREN SYNDROME | Micale et al. (2008) | Clearance of aggresomes polyubiquitinated | Fusco et al. (2014) |
| TRIP12 | 617752 | CLARK-BARAITSER SYNDROME | Zhang et al. (2017) | Epithelial-mesenchymal transition, DNA repair | Challa et al. (2021); Lee et al. (2021) |
| UBE3A | 105830 | ANGELMAN SYNDROME | Kishino et al. (1997) | Antiviral immunity | Furumai et al. (2019) |
| UBE3B | 244450 | KAUFMAN OCULOCEREBROFACIAL SYNDROME | Basel-Vanagaite et al. (2012) | Cell proliferation | Li et al. (2020) |
| UBR1 | 243800 | JOHANSON-BLIZZARD SYNDROME | Zenker et al. (2005) | Protein quality control | Zenker et al. (2005) |
| UBR7 | 619189 | LI-CAMPEAU SYNDROME | Li et al. (2021) | NLR activation, Stem cell function | Zhang et al. (2019); Srivastava et al. (2021) |
The potential implication of the identified 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.