Table 1.
List of non-syndromic intellectual disability (NS-ID) genes expressed in immature excitatory neurons.
| Gene | Affymetrix ID | Non-syndromic/syndromic | Gene name | Gene function | Protein localization | E13.5 GFP− precursor RMA | E13.5 GFP+ neuron RMA | E14.5 GFP+ neuron RMA | E13.5 RMA fold-up | E14.5 RMA fold-up |
|---|---|---|---|---|---|---|---|---|---|---|
| ACSL4 | 10607089 | NS | Acyl-CoA synthetase long-chain family member 4 | Fatty acid metabolism | Mito | 8.3 | 8.5 | 8.0 | 1.2 | 0.8 |
| AFF2/FMR2 | 10599927 | NS | Fragile X mental retardation 2 | DNA binding protein/activator of transcription? | Nuc | 8.0 | 9.9 | 9.7 | 3.7 | 3.2 |
| AGTR2 | 10599001 | NS/S | Angiotensin II receptor, type 2 | G-protein-coupled receptor/programed cell death | PM | 5.4 | 5.3 | 5.5 | 0.9 | 1.0 |
| AP1S2 | 10603051 | NS/S | Adaptor-related protein complex 1 sigma 2 subunit | Clathrin recruitment and sorting/synaptic vesicles | Golgi | 8.8 | 9.3 | 9.2 | 1.4 | 1.3 |
| ARHGEF6 | 10604713 | NS | Rac/Cdc42 guanine nucleotide exchange factor 6 | GEF for Rac and Cdc42 | Cyto | 6.1 | 4.5 | 4.7 | 0.3 | 0.4 |
| ARX | 10600755 | NS/S | Aristaless related homeobox | Transcriptional regulation during development | Nuc | 9.8 | 7.2 | 7.4 | 0.2 | 0.2 |
| ATRX | 10606263 | NS/S | Transcriptional regulator ATRX | Chromatin remodeling | Nuc | 10.2 | 10.5 | 10.4 | 1.2 | 1.2 |
| BRWD3 | 10606393 | NS/S | Bromo domain and WD repeat protein 3 | JAK/STAT signaling in drosophila/chromatin modifier? | Nuc | 8.7 | 9.3 | 9.0 | 1.5 | 1.2 |
| CASK | 10603708 | NS/S | Calcium/calmodulin-dependent serine kinase | Kinase and scaffolding at synapses/MAGUK family protein | Syn, PM, Nuc, Cyto | 10.3 | 11.5 | 11.4 | 2.2 | 2.2 |
| CC2D1A | 10580100 | NS | Coiled-coil and C2 domain containing 1A | Transcriptional regulator/NF-κB pathway activator | Nuc, Cyto | 7.6 | 7.9 | 7.9 | 1.2 | 1.2 |
| CDH15 | 10576175 | NS/S | Cadherin 15 | Intercellular adhesion protein | PM | 7.1 | 7.0 | 7.1 | 0.9 | 1.0 |
| CRBN | 10546775 | NS | Cereblon | Expression of potassium channels | PM, Cyto | 9.4 | 10.0 | 9.8 | 1.5 | 1.3 |
| DLG3 | 10601062 | NS | Synapse-associated protein 102 | Post-synaptic density scaffold/MAGUK family protein | Syn, PM, ER, Cyto | 8.9 | 9.5 | 9.5 | 1.5 | 1.5 |
| DOCK8 | 10462140 | Dedicator of cytokinesis 8 | GEF?/F-actin organization | PM, Cyto, Nuc | 6.1 | 6.1 | 6.1 | 1.0 | 1.0 | |
| FGD1 | 10602401 | NS/S | Faciogenital dysplasia protein | GEF for Cdc42 | Cyto | 9.3 | 9.1 | 9.2 | 0.9 | 0.9 |
| FTSJ1 | 10603508 | NS | FtsJ homolog 1 | rRNA processing | Nuc | 9.8 | 9.9 | 9.7 | 1.1 | 0.9 |
| GDI1 | 10600390 | NS | GDP dissociation inhibitor 1 | Inhibitor of Rab GTPases | Cyto | 11.7 | 12.8 | 12.5 | 2.2 | 1.8 |
| GRIK2 | 10368999 | NS | Glutamate receptor, ionotropic„ kainate 2 | Subunit of glutamate receptor (kainate) | PM, Syn | 9.7 | 10.2 | 9.2 | 1.4 | 0.7 |
| HUWE1 | 10602501 | NS/S | HECT, UBA, and WWE domain containing 1 | Ubiquitin E3 ligase/protein ubiquitination | Nuc, Cyto | 10.5 | 10.5 | 10.6 | 1.0 | 1.0 |
| IL1RAPL1 | NA | NS | Interleukin 1 receptor accessory protein-like 1 | Vesicle release/dendrite differentiation | PM | NA | ||||
| JARID1C/KDM5C | 10602644 | NS | Jumonji, AT rich interactive domain 1C | Transcriptional regulation/chromatin remodeling | Nuc | 9.9 | 9.8 | 10.0 | 0.9 | 1.1 |
| KIRREL3 | 10584165 | NS/S | Kin of IRRE like 3 | Synaptogenesis? | PM, Cyto, EC | 7.5 | 8.9 | 9.3 | 2.5 | 3.3 |
| MAGT1 | 10606301 | NS | Magnesium transporter 1 | Mg2+ uptake/N-glycosylation | ER | 10.4 | 8.5 | 8.2 | 0.3 | 0.2 |
| MBD5 | 10471967 | NS/S | Methyl-CpG binding domain protein 5 | Transcriptional regulation? | Nuc | 7.8 | 8.5 | 8.5 | 1.6 | 1.6 |
| MECP2 | 10605247 | NS/S | Methyl-CpG binding protein 2 | Transcriptional regulation | Nuc | 8.8 | 9.0 | 9.1 | 1.1 | 1.2 |
| NLGN4X | 10601152 | NS | X-linked neuroligin 4 | Synaptic adhesion protein | PM, Syn | 9.5 | 9.9 | 9.8 | 1.3 | 1.2 |
| OPHN1 | 10605884 | NS/S | Oligophrenin 1 | Rho-GTPase activating protein | Cyto | 8.2 | 9.3 | 9.3 | 2.2 | 2.1 |
| PAK3 | 10602198 | NS | p21-activated kinase 3 | Effector of Rho-GTPases | Cyto | 9.9 | 10.1 | 9.9 | 1.1 | 1.0 |
| PQBP1 | 10603373 | NS/S | Polyglutamine binding protein 1 | Transcriptional regulation | Nuc, Cyto | 10.9 | 11.3 | 10.8 | 1.3 | 1.0 |
| PRSS12 | 10495854 | NS | Neurotrypsin | Synaptic protease/cleaves agrin/synaptic plasticity | EC | 6.9 | 7.3 | 7.1 | 1.3 | 1.2 |
| PTCHD1 | 10607486 | NS | Patched domain 1 | Hedgehog receptor? | PM | 6.4 | 6.5 | 6.4 | 1.1 | 0.9 |
| RPS6KA3 | 10602772 | NS/S | Ribosomal protein S6 kinase, 90kDa, polypeptide 3 | Ras/Map/ERK regulation | Cyto | 9.8 | 9.8 | 9.6 | 1.0 | 0.9 |
| SHANK2 | 10559343 | NS | SH3 and multiple ankyrin repeat domains 2 | Scaffolding and cell adhesion protein/synaptic plasticity | Cyto, Syn | 7.1 | 7.7 | 7.9 | 1.5 | 1.7 |
| SHROOM4 | 10598240 | NS/S | Shroom family member 4 | Cytoskeletal architecture | Cyto | 6.2 | 5.7 | 5.8 | 0.7 | 0.8 |
| SLC6A8 | 10600210 | NS | Solute carrier family 6 member 8 | Creatine transporter | PM | 8.4 | 8.3 | 8.5 | 0.9 | 1.1 |
| STXBP1 | 10481711 | NS | Syntaxin-binding protein 1 | Synaptic vesicle docking and fusion/neurotransmission | PM, Syn, Cyto | 8.6 | 10.8 | 10.9 | 4.6 | 5.0 |
| SYNGAP1 | 10443091 | NS | Synaptic Ras GTPase activating protein 1 | NMDA receptor complex/Ras/Map/ERK regulation | PM, Syn | 9.6 | 10.2 | 10.7 | 1.6 | 2.1 |
| SYP | 10598359 | NS/S | Synaptophysin | Synaptic vesicle protein | Syn | 8.8 | 10.9 | 10.6 | 4.2 | 3.5 |
| TSPAN7 | 10598626 | NS/S | Tetraspanin 7 | Synapse maturation? | PM, Syn | 11.9 | 11.7 | 11.2 | 0.8 | 0.6 |
| TRAPPC9 | NA | NS | NIK- and IKKB-binding protein | Neuronal NF-κB signaling/vesicular transport | Golgi, ER, Cyto | NA | ||||
| TUSC3 | 10571371 | NS | Tumor suppressor candidate 3 | Mg2+ uptake/oligosaccharide transferase/N-glycosylation | ER | 9.3 | 10.2 | 10.2 | 1.8 | 1.8 |
| UPF3B | 10604078 | NS/S | UPF3 regulator of nonsense transcripts homolog B | mRNA nuclear export and surveillance | Nuc, Cyto | 7.9 | 8.1 | 8.0 | 1.1 | 1.1 |
| ZNF41/zfp27 56% | NA | NS | Zinc finger protein 41 | Putative repressor of transcription | Nuc | NA | ||||
| ZNF674/zfp182 56% | 10603881 | NS | Zinc finger protein 674 | Putative repressor of transcription | Nuc | 6.9 | 7.5 | 7.2 | 1.5 | 1.2 |
| ZNF711/zfp711 98% | 10601492 | NS | Zinc finger protein 711 | Activator of transcription? | Nuc | 8.6 | 9.7 | 9.4 | 2.1 | 1.7 |
| ZNF81/zfp160 47.4% | 10442172 | NS | Zinc finger protein 81 | Repressor of transcription? | Nuc | 8.3 | 8.9 | 8.6 | 1.5 | 1.2 |
A dataset of genes expressed by immature mouse cortical neurons at E13.5 and E14.5 (26) was queried for the expression of human NS-ID orthologs identified in (30). The expression values are reported as RMA (robust multichip average) as a log2 scale (e.g., RMA 9.0 is twofold higher than RMA 8.0). The fold-up values are derived from comparing the expression of the gene in the GFP+ neuronal population to the expression of the gene in GFP-neural precursors. Highlighted rows identify genes that are either not represented in the mouse data set (NA) or are expressed at levels below threshold (RMA = 7.0). Mouse zinc finger protein (Zfp) orthologs are listed with their percent amino acid identity to the corresponding human zinc finger protein (ZNF). The human NS-ID table is modified from Kaufman et al. (30) with permission.
EC, extracellular; ER, endoplasmic reticulum; Golgi, Golgi apparatus; Syn, synapse; PM, plasma membrane; Nuc, nucleus; Mito, mitochondria.