Table 2.
Forty-two potential pathogenic novel ABC mutations were identified in 151 Han Chinese patients with ICP disease
| ID | Gene | Patients | Chr | Position | Alleles | Protein change | SIFTd | Mutation Tastere | FATHMM | Comprehensive prediction resultf | GERP++NRg | PhastCons100way_verh | MAF in controls | MAF in 151 ICP | P value (controls-ICP) | MAF in databases |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | ABCA4 | ICP76 | chr1 | 94,522,278 | A/G | Phe754Ser | 0.001 (D) | 0.999 (D) | −4.24 (D) | Damaging | 5.66 | 1 | 0/(2*1029) | 10.60% (16/151) | 1.10E-14 | Absent in 1000G/ExAC/dbSNP/ChinaMAP databases |
| 2 | ABCA12a,b | ICP75 | chr2 | 215,809,749 | C/T | Cys2440Tyr | 0.041 (D) | 1 (D) | −3.67 (D) | Damaging | 5.49 | 1 | ||||
| 3 | ABCA13a | ICP112 | chr7 | 48,354,004 | C/G | Ser3286Ter | – | 1 (A) | – | Damaging | 5.68 | 1 | ||||
| 4 | ABCB1 | ICP121 | chr7 | 87,173,579 | G/A | Pro693Ser | 0.031 (D) | 1 (D) | −2.21 (D) | Damaging | 5.91 | 1 | ||||
| 5 | ABCB4 | ICP21 | chr7 | 87,053,310 | C/T | Trp708Ter | – | 1 (A) | – | Damaging | 6.11 | 1 | ||||
| 6 | ABCB4a,b | ICP154 | chr7 | 87,069,134 | C/T | Gly527Glu | 0.0 (D) | 1 (D) | −2.35 (D) | Damaging | 5.61 | 0.999 | ||||
| 7 | ABCB4a,b | ICP133,135 | chr7 | 87,073,053 | T/C | Lys386Glu | 0.002 (D) | 1 (D) | −2.65 (D) | Damaging | 5.47 | 0.999 | ||||
| 8 | ABCB5a,b | ICP47 | chr7 | 20,767,985 | G/T | Ser925Ile | 0.002 (D) | 0.786 (D) | −2.5 (D) | Damaging | 3.91 | 0.999 | ||||
| 9 | ABCB11 | ICP115 | chr2 | 169,783,704 | G/A | Gln1194Ter | – | 1 (A) | – | Damaging | 5.72 | 0.993 | ||||
| 10 | ABCB11 | ICP118 | chr2 | 169,826,057 | T/G | Gln605Pro | 0.006 (D) | 0.972 (D) | −1.99 (D) | Damaging | 5.5 | 0.835 | ||||
| 11 | ABCB11a,b | ICP2 | chr2 | 169,826,599 | G/T | Leu589Met | 0.0 (D) | 0.994 (D) | −2.82 (D) | Damaging | 5.2 | 0.959 | ||||
| 12 | ABCC2a,b,c | ICP79 | chr10 | 101,605,418 | C/A | Ser1342Tyr | 0.0 (D) | 0.999 (D) | −2.95 (D) | Damaging | 5.79 | 1 | ||||
| 13 | ABCC3a,b | ICP93 | chr17 | 48,755,166 | T/C | Ile1147Thr | 0.0 (D) | 1 (D) | −2.57 (D) | Damaging | 5.7 | 1 | ||||
| 14 | ABCC9a,b | ICP124 | chr12 | 22,061,100 | C/T | Ala456Thr | 0.001 (D) | 1 (D) | −2.58 (D) | Damaging | 5.29 | 1 | ||||
| 15 | ABCG2a,b | ICP6 | chr4 | 89,013,418 | G/T | Leu646Met | 0.01 (D) | 0.998 (D) | −2.33 (D) | Damaging | 5.55 | 1 | ||||
| 16 | ABCA2a,b | ICP64 | chr9 | 139,910,497 | G/C | Asp1108Glu | 0.043 (D) | 0.999 (N) | −3.27 (D) | Pro damaging | 4.2 | 1 | 0/(2*1029) | 13.91% (21/151) | 2.20E-16 | Absent in 1000G/ExAC/dbSNP/ChinaMAP databases |
| 17 | ABCA2 | ICP19 | chr9 | 139,913,419 | G/A | Ala583Val | 0.351 (T) | 0.999 (D) | −2.17 (D) | Pro damaging | 4.31 | 0.94 | ||||
| 18 | ABCA5 | ICP102 | chr17 | 67,266,794 | A/G | Val997Ala | 0.527 (T) | 0.961 (D) | −1.77 (D) | Pro damaging | 5.45 | 1 | ||||
| 19 | ABCA7 | ICP108 | chr19 | 1,045,131 | C/A | Pro449His | 0.015 (D) | 1 (N) | −4.44 (D) | Pro damaging | 3.05 | 0 | ||||
| 20 | ABCA8 | ICP47 | chr17 | 66,938,153 | A/G | Val8Ala | 0.009 (D) | 0.984 (N) | −2.41 (D) | Pro damaging | 4.84 | 0.018 | ||||
| 21 | ABCA10a,b | ICP35 | chr17 | 67,212,035 | A/G | Leu260Ser | 0.038 (D) | 1 (N) | −2.28 (D) | Pro damaging | 3.21 | 0.003 | ||||
| 22 | ABCA12 | ICP95 | chr2 | 215,865,543 | A/G | Ile1022Thr | 0.093 (T) | 0.994 (D) | −3.77 (D) | Pro damaging | 5.73 | 1 | ||||
| 23 | ABCA13 | ICP18 | chr7 | 48,559,709 | C/G | Leu4624Val | 0.017 (D) | 0.954 (N) | −2.477 (D) | Pro damaging | 5.35 | 0.702 | ||||
| 24 | ABCA13 | ICP107 | chr7 | 48,634,399 | A/G | Thr4912Ala | 0.001 (D) | 0.958 (N) | −5.88 (D) | Pro damaging | 5.7 | 1 | ||||
| 25 | ABCB9 | ICP112 | chr12 | 123,430,667 | C/T | Glu386Lys | 0.891 (T) | 0.682 (D) | −2.4 (D) | Pro damaging | 5 | 0.979 | ||||
| 26 | ABCB9 | ICP140 | chr12 | 123,433,209 | T/C | Ile339Val | 0.176 (T) | 0.999 (D) | −2.6 (D) | Pro damaging | 5.43 | 1 | ||||
| 27 | ABCC1 | ICP98 | chr16 | 16,149,964 | A/G | Ser497Gly | 0.268 (T) | 0.972 (D) | −2.71 (D) | Pro damaging | 5.32 | 1 | ||||
| 28 | ABCC3 | ICP57 | chr17 | 48,734,467 | C/T | Leu137Phe | 0.011 (D) | 1 (D) | 0.85 (T) | Pro damaging | 5.38 | 1 | ||||
| 29 | ABCC5 | ICP49 | chr3 | 183,670,989 | T/G | Gln851Pro | 0.026 (D) | 0.999 (D) | 0.95 (T) | Pro damaging | 5.62 | 1 | ||||
| 30 | ABCC6 | ICP57 | chr16 | 16,259,657 | G/T | His1043Gln | 0.029 (D) | 0.999 (N) | −3.35 (D) | Pro damaging | 5.52 | 1 | ||||
| 31 | ABCC9 | ICP36 | chr12 | 21,968,809 | T/A | Glu1304Val | 0.111 (T) | 0.999 (D) | −2.61 (D) | Pro damaging | 4.95 | 1 | ||||
| 32 | ABCC12 | ICP155 | chr16 | 48,180,227 | G/A | Pro37Ser | 0.217 (T) | 0.812 (D) | −2.76 (D) | Pro damaging | 5.45 | 0.974 | ||||
| 33 | ABCD4 | ICP95 | chr14 | 74,757,137 | G/A | Ser395Phe | 0.033 (D) | 0.983 (N) | −2.77 (D) | Pro damaging | 4.84 | 0.875 | ||||
| 34 | ABCD4 | ICP142 | chr14 | 74,757,168 | T/C | Thr385Ala | 0.254 (T) | 0.990 (D) | −2.63 (D) | Pro damaging | 4.84 | 1 | ||||
| 35 | ABCF2 | ICP84 | chr7 | 150,923,406 | C/T | Gly47Ser | 0.156 (T) | 0.999 (D) | −2.77 (D) | Pro damaging | 4.81 | 1 | ||||
| 36 | ABCG1a,b | ICP113 | chr21 | 43,704,752 | A/G | Ile273Val | 0.002 (D) | 1 (D) | 0.52 (T) | Pro damaging | 4.22 | 1 | ||||
| 37 | ABCA3 | ICP22 | chr16 | 2,348,506 | T/C | Ser593Gly | 0.126 (T) | 1 (N) | −3.3 (D) | Pos damaging | 6.17 | 0.005 | 0/(2*1029) | 3.31% (5/151) | 3.74E-08 | Absent in 1000G/ExAC/dbSNP/ChinaMAP databases |
| 38 | ABCA10 | ICP64 | chr17 | 67,181,648 | G/C | Leu823Val | 0.09 (T) | 1 (N) | −2.19 (D) | Pos damaging | 2.92 | 0.011 | ||||
| 39 | ABCA12 | ICP71 | chr2 | 215,802,301 | T/C | Asn2492Ser | 0.403 (T) | 0.958 (N) | −2.28 (D) | Pos damaging | 5.79 | 0.999 | ||||
| 40 | ABCA13 | ICP111 | chr7 | 48,349,554 | G/A | Ser3111Asn | 0.071 (T) | 0.999 (N) | −2.11 (D) | Pos damaging | 5.59 | 0.354 | ||||
| 41 | ABCG1 | ICP22 | chr21 | 43,708,158 | C/T | Thr378Ile | 0.21 (T) | 1 (N) | −1.98 (D) | Pos damaging | 4.17 | 0 | ||||
| 42 | ABCA13 | ICP52 | chr7 | 48,318,169 | A/G | Ile2460Val | 0.916 (T) | 1 (N) | 0.66 (T) | Neutral | 4.92 | 0 | 0/(2*1029) | 0.66% (1/151) | 0.13 | Absent in 1000G/ExAC/dbSNP/ChinaMAP databases |
a These loci were validated by Sanger sequencing
b These loci were identified by evolutionary conservation analysis
c The effect of the change in this mutation on the encoded protein structure
d D: disease-causing, T: tolerated
e N: polymorphism, A: automatically disease causing
f Pro damaging: probably damaging; Pos damaging: possibly damaging
g GERP++NR: GREP++ conservation score. The higher the value is, the more conservative the loci
h PhastCons100way_ver: conservative prediction in 100 vertebrates. The scores of the PhastCons score ranged from 0 to 1, and the higher the values are, the more conservative the loci