Table 2.
Novel candidate genes for intellectual disability
| Family | Ethnicity | Genes | Position a | Transcript | cDNA mutation | Protein change | Variation | Protein function | CADD score v1.3 | ExAC allele frequency x10 − 6 |
|---|---|---|---|---|---|---|---|---|---|---|
| PKMR24 | Punjabi | ZSCAN25 (ZNF498) | Chr7:99219114A>G | NM_145115.2 | c.506A>G | p.(Glu169Gly) | Missense | Zinc finger protein nucleic acid binding | 26.5 | 0 |
| PKMR33 | Punjabi | DPH1 | Chr17:1944817C>T | NM_001383.3 | c.1144C>T | p.(Pro382Ser) | Missense | Diphthamide biosynthesis | 32 | 8.515 |
| PKMR40 | Pathan | DCTN2 | Chr12:57929561T>G | NM_001261412.1 | c.173A>C | p.(Lys58Thr) | Missense | Structural protein | 26.8 | 8.484 |
| PKMR43 | Pathan | METTL5 | Chr2:170677663_64delTC | NM_014168.3 | c.344_345delGA | p.(Arg115Asnfs*19) | Frameshift | Methyl transferase | NA | 0 |
| PKMR45 | Pathan | TANGO2 (C22orf25) | Chr22:20041047G>T | NM_152906.5 | c.353G>T | p.(Gly118Val) | Missense | Transport and Golgi organization | 29.4 | 0 |
| PKMR64 | Punjabi | CAPN12 b | Chr19:39230761_62delTT | NM_144691.4 | c.658_659delAA | p.(Asn220Glnfs*25) | Frameshift | Cystine protease | NA | 795.1 |
| PKMR66 | Punjabi | TBC1D8 | Chr2:101652537G>A | NM_001102426.1 | c.1501C>T | p.(Leu501Phe) | Missense | G-protein modulator | 31.0 | 99.37 |
| PKMR67 | Punjabi | MSS51 (ZMYND17) | Chr10:75187870G>A | NM_001024593.1 | c.173C>T | p.(Ser58Leu) | Missense | Zinc finger transcription factor | 33.0 | 140.1 |
| PKMR72 | Punjabi | MDGA2 | Chr14:47343402T>C | NM_001113498.2 | c.2232A>G | p.(Arg744Arg) | Aberrant Splicing | GPI anchor | NA | 52.83 |
| PKMR98 | Punjabi | FMOD | Chr1:203316893C>T | NM_002023.4 | c.506G>A | p.(Arg169Gln) | Missense | Receptor | 23.3 | 296.6 |
| PKMR118 | Punjabi | C22orf31 | Chr22:29454885C>G | NM_015370.1 | c.718G>C | p.(Gly240Arg) | Missense | Unknown | 28.6 | 0 |
| PKMR142 | Punjabi | SMARCA1 | ChrX:128657269C>T | NM_139035.2 | c.79G>A | p.(Glu27Lys) | Missense | Component of NURF complex | 22.1 | 35.55 |
| PKMR153 | Punjabi | GPAA1 | Chr8:145138854G>C | NM_003801.3 | c.527G>C | p.(Trp176Ser) | Missense | Glycosylphosphatidylinositol | 27.6 | 16.58 |
| PKMR155 | Kashmiri | OR2A12 | Chr7:143792562G>A | NM_001004135.1 | c.362G>A | p.(Arg121Gln) | Missense | Olfactory receptor | 24.1 | 16.57 |
| PKMR159 | Punjabi | AACS | Chr12:125612785A>G | NM_023928.3 | c.1388A>G; | p.(Asn463Ser); | Missense | Acetoacetyl-Co synthetase | 21.2 | 82.95 |
| Chr12:125621351C>T | c.1822C>T | p.(Arg608Cys) | Missense | 34.0 | 198.1 | |||||
| PKMR164 | Punjabi | GGN | Chr19:38877823G>A | NM_152657.3 | c.79C>T | p.(Arg27Cys) | Missense | Germ cell specific gene | 25.9 | 362.3 |
| PKMR174 | Siraki | MEGF9 | Chr9:123421769C>T | NM_001080497.2 | c.686G>A | p.(Gly229Asp) | Missense | Receptor | 26.8 | 59.54 |
| PKMR195 | Siraki | WFDC1 | Chr16:84360517G>A | NM_021197.3 | c.634G>A | p.(Gly212Arg) | Missense | Protease inhibitor | 24.2 | 65.89 |
| PKMR198 | Punjabi | METTL4 | Chr18:2554909G>T | NM_022840.4 | c.588C>A | p.(Cys196*) | Nonsense | Methyl transferase | NA | 41.19 |
| PKMR200 | Siraiki | UBE2J2 | Chr1:1203295_96delTT | NM_194315.1 | c.77_78delAA | p.(Lys26Argfs*30) | Frameshift | Ubiquitin protein ligase | NA | 0 |
| PKMR206 | Siraiki | CCDC82 | Chr11:96117539delC | NM_024725.3 | c.373delG | p.(Asp125Ilefs*6) | Frameshift | Unknown | NA | 0 |
| PKMR213 | Siraiki Baloch | TMEM222 | Chr1:27657230G>A | NM_032125.2 | c.214G>A | p.(Gly72Ser) | Missense | Transmembrane protein | 34.0 | 8.237 |
| PKMR215 | Siraiki | PUS7 | chr7:105148870_71delTG | NM_019042.3 | c.89_90delCA | p.(Thr30Lysfs*20) | Frameshift | Pseudouridylate synthetase | NA | 8.237 |
| PKMR258 | Punjabi | AREL1 | Chr14:75150203G>A | NM_001039479.1 | c.277C>T | p.(His93Tyr) | Missense | Ubiquitin-protein ligase | 23.1 | 1102 |
| PKMR298 | Punjabi | SEPT6 | ChrX:118797529T>C | NM_145799.3 | c.257A>G | p.(Tyr86Cys) | Missense | Filament formation | 26.4 | 11.41 |
| PKMR318 | Punjabi | DUOX1 | Chr15:45444197G>T | NM_175940.2 | c.3140G>T | p.(Cys1047Phe) | Missense | Oxidase | 22.9 | 16.59 |
| PKMR320 | Punjabi | SLC7A10 | Chr19:33700282_83dupA | NM_019849.2 | c.1372_1373dupA | p.(Thr458Asnfs*71) | Frameshift | Transporter | NA | 16.49 |
| PKMR325 | Punjabi | TM2D3 | Chr15:102182749G>A | NM_078474.2 | c.677C>T | p.(Thr226Met) | Missense | Cell death or proliferation | 31.0 | 8.344 |
| PKMR326 | Pathan | PRKAR2B | Chr7:106797706G>T | NM_002736.2 | c.1060G>T | p.(Ala354Ser) | Missense | Kinase modulator | 32.0 | 8.247 |
| PKMR396 | Punjabi | RGR | Chr10:86008779G>A | NM_002921.3 | c.350G>A | p.(Arg117His) | Missense | Retinal G-protein coupled receptor | 26.5 | 107.3 |
Abbreviations: GPI, Glycophosphatidylinositol; NA, Not Applicable.
aChromosomal position according to GRCh37/hg19.
bThis frameshift allele of CAPN12 has been documented in apparently healthy British–Pakistani individual in a homozygous fashion.35