Rare monogenic forms of ID linked to mutations of components or regulators of the ubiquitin pathway
Gene | Protein | Disease | Genetic abnormalities | References |
---|---|---|---|---|
ASXL3 | Component of the Polycomb repressive deubiquitination (PR-DUB) complex | Bainbridge–Ropers syndrome, BRS (OMIM 615485) and ASD | De novo truncating mutations in BRS and missense mutations in ASD | Bainbridge et al. (2013); De Rubeis et al. (2014) |
CUL4B | Scaffolding protein stabilizing cullin RING E3 ligase | XLID (OMIM 300304) | Missense mutations | Wang et al. (2013); Zou et al. (2007) |
HECW2 | E3 ubiquitin ligase HECW2 | Neurodevelopmental disorder with hypotonia, seizures, and absent language, NDHSAL (OMIM 617268) | Missense mutations | Halvardson et al. (2016) |
HERC1 | E3 ubiquitin ligase HERC1 | Macrocephaly, dysmorphic facies, and psychomotor retardation, MDFPMR (OMIM 617011) | Missense and frameshift mutations | Aggarwal et al. (2016); Nguyen et al. (2016); Ortega-Recalde et al. (2015) |
HERC2 | E3 ubiquitin ligase HERC2 | Syndrome of ID, autism, and variable neurological deficits (OMIM 615516) | Missense mutations | Puffenberger et al. (2012) |
HUWE1 | HECT, UBA, and WWE domain containing 1, E3 ubiquitin protein ligase | Turner type, XLID (OMIM 309590) | Microduplications, missense mutations | Froyen et al. (2008); Moortgat et al. (2018) |
MAGEL2 | E3 ubiquitin ligase enhancer | Prader–Willi syndrome, PWS (OMIM 176270) and Schaaf–Yang syndrome, SHFYNG (OMIM 615547) | Interstitial deletions and maternal uniparental disomy in PWS; truncating mutations in SHFYNG | Tacer and Potts (2017) |
MID2 | Member of the TRIpartite motif (TRIM) family of RING E3 ligases | XLID (OMIM 300928) | Missense mutation | Geetha et al. (2014) |
OTUD6B | Member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, IDDFSDA (OMIM 617452) | Truncating and missense mutations | Santiago-Sim et al. (2017) |
PLAA | Ubiquitin binding protein phospholipase A2 activating protein | Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, NDMSBA (OMIM 617527) | Missense mutations | Falik Zaccai et al. (2017); Hall et al. (2017) |
RLIM | RNF12 E3 ubiquitin ligase | Tonne–Kalscheuer syndrome, XLID (OMIM 300978) | Missense mutation | Tønne et al. (2015) |
TRIM50 | Member of the TRIpartite motif (TRIM) family of RING E3 ligases | William–Beuren syndrome, WBS (OMIM 194050) | Microdeletion on chr. 7q11.23 | Micale et al. (2008) |
TRIP12 | Member of the HECT domain E3 ubiquitin ligases family | ID with or without ASD (OMIM 6177520) | CNVs, missense, frameshift, splicing mutations | Zhang et al. (2017) |
UBE2A | E2 ubiquitin conjugating enzyme E2A | XLID type Nascimento (OMIM 300860) | Truncating and missense mutations | Budny et al. (2010); Nascimento et al. (2006) |
UBE3B | E3 ubiquitin ligase E3B | Blepharophimosis-ptosis-ID syndrome, BPIDS (OMIM 244450) | Truncating mutations | Basel-Vanagaite et al. (2012) |
USPX9 | Deubiquitinating enzyme FAF-X | Female-restricted X-linked non-syndromic mental retardation-99 (OMIM 300919) | Truncating mutation and X-chr. deletion | Au et al. (2017) |
XLID: X-linked ID, CNV: copy number variation.