Table 3 Potential defects identified using our mutational annotation pipeline in aaRSs
Disease | aaRS/mutations | Previous functional annotation for mutation | Structural/functional feature potentially affected (category for mutational annotation) |
|---|---|---|---|
Charcot-Marie-Tooth disorder (CMT) | GRS (Ala111Val) | No reported annotation | Un-annotated (d) |
GRS (Glu125Gly) | No reported annotation | Dimerization (c) | |
GRS (Pro152Leu) | No reported annotation | Dimerization (c) | |
GRS (Leu183Pro) | Defective dimerization | Dimerization (c) | |
GRS (Cys211Arg) | No reported annotation | Structural stability (b) | |
GRS (Pro288Lys) | No reported annotation | Dimerization (c) | |
GRS (Gly294Arg) | Defective dimerization | Structural stability (b) | |
GRS (Pro298Leu) | No reported annotation | Structural stability (b) | |
GRS (Ile334Phe) | No reported annotation | Dimerization (c) | |
GRS (His472Arg) | No reported annotation | Structural stability (b) | |
GRS (Asp554Asn) | Enhanced dimerization | Un-annotated (d) | |
GRS (Gly580Arg) | Enhanced dimerization | Structural stability (b) | |
GRS (Ser635Leu) | Enhanced dimerization | Inter-molecular interaction (c) | |
GRS (Gly652Ala) | No reported annotation | Inter-molecular interaction (c) | |
YRS (Gly41Arg) | Impaired tyrosine activation | ATP/amino-acid binding (a) | |
YRS (Glu196Lys) | No reported annotation | Structural stability (b) | |
ARS (Asn71Tyr) | Impaired tRNA charging | Structural stability (b) | |
ARS (Arg329His) | Imparired tRNA charging | Structural stability (b) | |
ARS (Glu778Ala) | No reported annotation | Un-annotated (d) | |
ARS (Asp893Asn) | No reported annotation | Un-annotated (d) | |
KRS (Leu133His) | Decreased enzyme activity | Structural stability (b) | |
KRS (Ile302Met) | No reported annotation | Inter-molecular interactions (c) | |
KRS (Thr623Ser) | No reported annotation | Un-annotated (d) | |
Infantile hepatopathy | LRS (Lys82Arg) | No reported annotation | Un-annotated (d) |
LRS (Tyr373Cys) | No reported annotation | Structural stability (b) | |
Type-2 diabetes | LRS (His324Gln) | No reported annotation | Structural stability (b) |
Perrault syndrome, ovarian failure and hearing loss | LRS (Thr522Asn) | Decreased enzyme activity | Structural stability (b) |
LRS (Thr629Met) | No reported annotation | Structural stability (b) | |
HRS (Leu200Val) | Decrease enzyme activity | Structural stability (b) | |
HRS (Val368Leu) | Decreased enzyme activity | Structural stability (b) | |
Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) | YRS (Gly46Asp) | Translational defects | Inter-molecular interactions (c) |
YRS (Phe52Leu) | Abnormal enzyme kinetics | Inter-molecular interactions (c) | |
HUPRA syndrome | SRS (Asp390Gly) | Decreased enzyme activity | Structural stability (b) |
SRS (Arg402His) | No reported annotation | Structural stability (b) | |
Infantile cardiomyopathies | ARS (Leu155Arg) | No reported annotation | Un-annotated (d) |
ARS (Arg592Trp) | No reported annotation | Un-annotated (d) | |
Ponto cerebellar hypoplasia | RRS (Ile9Val) | No reported annotation | Un-annotated (d) |
RRS (Gln12Arg) | No reported annotation | Un-annotated (d) | |
RRS (Trp241Arg) | No reported annotation | Structural stability (b) | |
RRS (Arg245Gln) | No reported annotation | Structural stability (b) | |
RRS (Arg469His) | No reported annotation | tRNA binding (a) | |
Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) | ERS (Arg55His) | No reported annotation | Structural stability (b) |
ERS (Glu96Lys) | No reported annotation | Inter-molecular interactions (c) | |
ERS (Arg107His) | No reported annotation | Inter-molecular interactions (c) | |
ERS (Arg108Trp) | No reported annotation | Inter-molecular interactions (c) | |
ERS (Gly110Ser) | No reported annotation | Inter-molecular interactions (c) | |
ERS (Lys167Tyr) | No reported annotation | Un-annotated (d) | |
ERS (Arg168Gly) | No reported annotation | Un-annotated (d) | |
ERS (Gly204Ser) | No reported annotation | Inter-molecular interactions (c) | |
ERS (Gly224Ser) | No reported annotation | Inter-molecular interactions (c) | |
ERS (Gly317Cys) | No reported annotation | tRNA binding (a) | |
ERS (Arg516Gln) | No reported annotation | Structural stability (b) | |
DRS (Ser45Gly) | No reported annotation | Dimerization (c) | |
DRS (Cys152Phe) | Defective dimerization | Dimerization (c) | |
DRS (Arg179His) | No reported annotation | Inter-molecular interactions (c) | |
DRS (Leu239Pro) | No reported annotation | Un-annotated (d) | |
DRS (Arg263Gln) | Defective dimerization | Dimerization (c) | |
DRS (Leu613Phe) | No reported annotation | tRNA binding (a) | |
DRS (Leu626Gln) | Decrease enzyme activity | Inter-molecular interactions (c) | |
DRS (Leu626Val) | No reported annotation | Inter-molecular interactions (c) | |
Fatal infantile Alpers encephalopathy, mitochondrial myopathies | FRS (Tyr144Cys) | Defective tRNA binding | Un-annotated (d) |
FRS (Ile329Thr) | Impaired stability/decreased ATP binding | Structural stability (b) | |
FRS (Asp391Val) | Impaired stability/decreased Phe binding | Inter-molecular interactions (c) |