Table 1. A 72-member constrained gene subnetwork.
We find that 67/107 significantly constrained genes form a single protein-protein interaction subnetwork. Five additional genes are also included (gray shading), as our cluster detection algorithm by design looks for a backbone of null nodes connected to many signal nodes. As shown in Fig 2, the subnetwork is significantly larger and more densely connected than expected by chance, and is preferentially expressed in a subset of early-stage neural and immune tissues.
| Gene | Constraint score | Chr | Start | End | Gene | Constraint score | Chr | Start | End |
|---|---|---|---|---|---|---|---|---|---|
| DYNC1H1 | 9.977 | 14 | 101964528 | 102050792 | UBR4 | 4.940 | 1 | 19074506 | 19210276 |
| PRPF8 | 8.302 | 17 | 1650629 | 1684882 | CHD3 | 4.905 | 17 | 7884806 | 7912760 |
| HUWE1 | 7.973 | X | 53532096 | 53686729 | USP7 | 4.866 | 16 | 8892094 | 8964514 |
| SMARCA4 | 6.604 | 19 | 10961001 | 11065395 | PRPF6 | 4.826 | 20 | 63981135 | 64033100 |
| POLR2A | 6.578 | 17 | 7484366 | 7514618 | GNAS | 4.806 | 20 | 58839718 | 58911192 |
| RYR2 | 6.436 | 1 | 237042205 | 237833988 | THOC2 | 4.791 | X | 123600561 | 123733056 |
| MED12 | 6.388 | X | 71118556 | 71142454 | FRY | 4.772 | 13 | 32031300 | 32299122 |
| SNRNP200 | 6.166 | 2 | 96274336 | 96305515 | OGT | 4.753 | X | 71533083 | 71575897 |
| CHD4 | 6.162 | 12 | 6570083 | 6607476 | POLR2B | 4.729 | 4 | 56977722 | 57031168 |
| MTOR | 5.974 | 1 | 11106535 | 11262507 | KCNMA1 | 4.687 | 10 | 76869601 | 77638595 |
| GRIN1 | 5.971 | 9 | 137138390 | 137168762 | TAOK1 | 4.685 | 17 | 29390464 | 29551904 |
| PPFIA3 | 5.794 | 19 | 49119389 | 49151026 | BRWD3 | 4.683 | X | 80670854 | 80809688 |
| MLL | 5.747 | 11 | 118436490 | 118526832 | SPTAN1 | 4.671 | 9 | 128552558 | 128633665 |
| UBR5 | 5.720 | 8 | 102253012 | 102412841 | PHIP | 4.670 | 6 | 78935867 | 79078236 |
| ITPR1 | 5.589 | 3 | 4493348 | 4847840 | DDB1 | 4.670 | 11 | 61299451 | 61342596 |
| CLTC | 5.547 | 17 | 59619689 | 59696956 | HSPA2 | 4.665 | 14 | 64535905 | 64546173 |
| FLNA | 5.541 | X | 154348524 | 154374638 | SPEG | 4.644 | 2 | 219434846 | 219498287 |
| UPF1 | 5.514 | 19 | 18831938 | 18868236 | SMC3 | 4.639 | 10 | 110567691 | 110604636 |
| HCFC1 | 5.450 | X | 153947553 | 153971807 | MYH10 | 4.629 | 17 | 8474205 | 8630761 |
| DHX30 | 5.428 | 3 | 47802909 | 47850195 | XPO1 | 4.621 | 2 | 61477849 | 61538626 |
| SPTBN1 | 5.423 | 2 | 54456285 | 54671445 | CUL3 | 4.610 | 2 | 224470150 | 224585397 |
| SF3B1 | 5.418 | 2 | 197389784 | 197435091 | IRS2 | 4.592 | 13 | 109752698 | 109786568 |
| SMARCA2 | 5.387 | 9 | 2015219 | 2193624 | ADCY1 | 4.587 | 7 | 45574140 | 45723116 |
| CACNA1I | 5.363 | 22 | 39570753 | 39689737 | APC2 | 4.564 | 19 | 1446302 | 1473244 |
| SMC1A | 5.360 | X | 53374149 | 53422728 | ZBTB17 | 4.547 | 1 | 15941869 | 15976132 |
| GRIN2B | 5.334 | 12 | 13537337 | 13980119 | TLN1 | 4.517 | 9 | 35696948 | 35732395 |
| GRIN2D | 5.211 | 19 | 48394875 | 48444931 | MYH9 | 4.496 | 22 | 36281281 | 36388018 |
| TAF1 | 5.178 | X | 71366239 | 71532374 | EEF2 | 4.478 | 19 | 3976056 | 3985469 |
| VCP | 5.162 | 9 | 35056064 | 35073249 | PDS5A | 4.451 | 4 | 39822863 | 39977956 |
| CNOT1 | 5.146 | 16 | 58519951 | 58629886 | PRKD2 | 4.438 | 19 | 46674275 | 46717127 |
| TRIO | 5.109 | 5 | 14143702 | 14532128 | BRD4 | 4.436 | 19 | 15235519 | 15332545 |
| CYFIP2 | 5.100 | 5 | 157266079 | 157395598 | HSPA8 | 4.364 | 11 | 123057489 | 123063230 |
| SUPT5H | 5.065 | 19 | 39436156 | 39476670 | CTNNB1 | 4.198 | 3 | 41194837 | 41260096 |
| FZD8 | 5.028 | 10 | 35638249 | 35642278 | UBC | 3.997 | 12 | 124911604 | 124917368 |
| TNPO2 | 4.993 | 19 | 12699194 | 12724011 | PIK3CD | 3.858 | 1 | 9651732 | 9729114 |
| GTF2I | 4.945 | 7 | 74657667 | 74760692 | PIK3R1 | 2.170 | 5 | 68215720 | 68301821 |