Table 1.
SFARI Class I and Class II ASD-relevant genes are translationally reduced in the Fmr1 KO mouse cortex.
| SFARI autism gene | Fold-change TE Fmr1 KO/WT | P-valueadj | # amino acids | Darnell et al. (2011) CLIP target | ClinGen haplo-insufficiency score | ClinGen triplo-sensitivity score |
|---|---|---|---|---|---|---|
| PRR12 | 0.51 | 0.0E+00 | 2,035 | ✓ | n/a | n/a |
| KMT2A | 0.58 | 9.0E−05 | 3,966 | ✓ | 3 | 0 |
| HIVEP3 | 0.58 | 4.7E−04 | 2,348 | ✓ | 1 | 0 |
| SHANK1 | 0.59 | 0.0E+00 | 2,167 | ✓ | 1 | 0 |
| SETD1B | 0.59 | 1.4E−03 | 1,985 | n/a | n/a | |
| KMT2C | 0.61 | 4.0E−08 | 4,904 | ✓ | 3 | 0 |
| SPEN | 0.63 | 2.7E−07 | 3,620 | ✓ | 1 | 0 |
| MED13L | 0.63 | 4.8E−08 | 2,207 | ✓ | 3 | 1 |
| TCF20 | 0.64 | 7.1E−07 | 1,987 | ✓ | 3 | 0 |
| SCAF4 | 0.64 | 6.1E−04 | 1,209 | n/a | n/a | |
| AHDC1 | 0.65 | 2.2E−07 | 1,594 | ✓ | 3 | 0 |
| SRCAP | 0.65 | 6.2E−07 | 3,271 | 1 | 0 | |
| CIC | 0.66 | 5.4E−07 | 1,604 | ✓ | 2 | 0 |
| KDM3B | 0.66 | 1.3E−06 | 1,762 | n/a | n/a | |
| CNOT3 | 0.66 | 5.0E−03 | 751 | 0 | 0 | |
| MAP1A | 0.67 | 0.0E+00 | 2,776 | ✓ | n/a | n/a |
| SHANK2 | 0.67 | 5.9E−08 | 1,472 | ✓ | 2 | 0 |
| RIMS1 | 0.67 | 9.7E−07 | 1,190 | 1 | 0 | |
| AUTS2 | 0.67 | 8.0E−06 | 1,261 | ✓ | 3 | 0 |
| RERE | 0.68 | 1.0E−03 | 1,558 | ✓ | n/a | n/a |
| SYN1 | 0.68 | 1.2E−06 | 670 | ✓ | 2 | 0 |
| HECTD4 | 0.68 | 0.0E+00 | 4,418 | n/a | n/a | |
| LRP1 | 0.69 | 0.0E+00 | 4,545 | ✓ | n/a | n/a |
| CAMK2A | 0.69 | 3.0E−04 | 478 | ✓ | 1 | 0 |
| CREBBP | 0.69 | 1.1E−06 | 2,441 | ✓ | 3 | 0 |
| NOVA2 | 0.70 | 2.6E−03 | 492 | n/a | n/a | |
| CHD8 | 0.70 | 2.7E−05 | 2,582 | ✓ | 3 | 0 |
| SHANK3 | 0.71 | 5.4E−03 | 1,805 | ✓ | 3 | 0 |
| ARID2 | 0.71 | 7.3E−04 | 1,828 | ✓ | 3 | 0 |
| ASH1L | 0.71 | 2.9E−09 | 2,958 | ✓ | 3 | 0 |
| IQSEC2 | 0.71 | 1.3E−05 | 1,479 | ✓ | 3 | 0 |
| ZC3H4 | 0.72 | 3.6E−03 | 1,255 | ✓ | n/a | n/a |
| SON | 0.72 | 5.2E−04 | 2,444 | ✓ | 3 | 0 |
| GRIK5 | 0.72 | 5.6E−03 | 979 | ✓ | n/a | n/a |
| CACNA1A | 0.72 | 1.6E−05 | 2,327 | ✓ | 3 | 0 |
| KIF5C | 0.73 | 1.4E−10 | 956 | ✓ | n/a | n/a |
| HUWE1 | 0.73 | 6.6E−10 | 4,378 | ✓ | 0 | 0 |
| ZMIZ1 | 0.74 | 1.5E−03 | 1,066 | ✓ | n/a | n/a |
| AKAP9 | 0.74 | 1.2E−03 | 3,779 | ✓ | n/a | n/a |
| NCOR1 | 0.74 | 4.1E−07 | 2,454 | ✓ | n/a | n/a |
| ARID1B | 0.75 | 1.8E−04 | 2,244 | ✓ | 3 | 0 |
| AGO2 | 0.76 | 1.2E−03 | 860 | n/a | n/a | |
| MYT1L | 0.77 | 6.6E−03 | 1,185 | ✓ | 3 | 0 |
| FOXG1 | 0.78 | 8.6E−03 | 481 | 3 | 0 | |
| MECP2 | 0.78 | 9.5E−03 | 484 | n/a | n/a | |
| WDFY3 | 0.78 | 6.5E−06 | 3,508 | ✓ | n/a | n/a |
| VAMP2 | 0.78 | 6.7E−05 | 116 | ✓ | n/a | n/a |
| NSD1 | 0.79 | 4.3E−03 | 2,691 | ✓ | 3 | 0 |
| CHD3 | 0.79 | 4.8E−04 | 2,055 | ✓ | n/a | n/a |
| EP400 | 0.80 | 8.2E−04 | 2,999 | ✓ | n/a | n/a |
| INTS1 | 0.80 | 5.2E−03 | 2,222 | ✓ | n/a | n/a |
| PHF3 | 0.80 | 2.7E−03 | 2,025 | 1 | 0 | |
| YWHAG | 0.80 | 5.8E−04 | 247 | ✓ | n/a | n/a |
| SLC12A5 | 0.81 | 5.0E−03 | 1,138 | ✓ | n/a | n/a |
| CTNND2 | 0.81 | 2.3E−04 | 1,221 | ✓ | 2 | 0 |
| SATB1 | 0.82 | 7.4E−03 | 764 | n/a | n/a | |
| TRRAP | 0.82 | 2.0E−04 | 3,847 | ✓ | 1 | 0 |
| NFIX | 0.82 | 5.5E−04 | 433 | ✓ | n/a | n/a |
| SYNE1 | 0.82 | 4.1E−03 | 1,431 | ✓ | n/a | n/a |
| TANC2 | 0.83 | 7.6E−03 | 1,994 | ✓ | n/a | n/a |
| ATP2B2 | 0.83 | 5.5E−04 | 1,198 | ✓ | n/a | n/a |
| ILF2 | 1.25 | 9.5E−03 | 390 | n/a | n/a |
Table showing SFARI Class I and Class II ASD−relevant genes that are significantly altered in their translation efficiency in the Fmr1 KO mouse brain. Ninety-eight percentage (61/62) of altered ASD-relevant genes are translationally reduced. ClinGen Dosage scores (Rehm et al. 2015) (3 = sufficient evidence, 2 = emerging evidence, 1 = little evidence, 0 = no evidence) show that many of these ASD-relevant genes have strong or emerging evidence of human syndromes associated with gene losses (haploinsufficiency) but not gene duplications (triplosensitivity). n/a, not available.