Biological functions of transcript isoforms and pharmacological implications
| Gene | Function/Role | Features | References |
|---|---|---|---|
| CETP | Lipid transport protein | Splicing affected by diet, dominant-negative | Yang et al., 1996; Dessi et al., 1997; Lira et al., 2008 |
| UGT1A | Drug metabolism | Alternative first exon usage and exon 5 splicing | Levesque et al., 2007; Gong et al., 2001 |
| CACNA1C | Target in hypertension, arrhythmia treatment | Splice variants have different expression patterns and dihydropyridines sensitivity | Welling et al., 1997Tang et al., 2004; ; Wang et al., 2006 |
| DRD2 | Antipsychotic drug target | Splice forms have different drug sensitivity | Malmberg et al., 1993; Usiello et al., 2000; Xu et al., 2002 |
| OPRM1 | Analgesics and narcotics receptor | Alternate exon 1 affects opioid analgesic effects | Schuller et al., 1999; Pan et al., 2005a,b, 2009 |
| COX-1 | NSAID target | Three splice isoforms, relevance in humans | Chandrasekharan et al., 2002; Kis et al., 2005; Qin et al., 2005 |
| MYD88 | Inflammation | Splice form lacking exon 2 (MyD88S) decreases inflammation | Janssens et al., 2002; Burns et al., 2003; Vickers et al., 2006 |
| TNFR | Inflammation | Exon exclusion produces soluble TNF receptor | Graziewicz et al., 2008 |
| NAT1 | Drug detoxification | Isoforms with different translation efficiencies | Boukouvala and Sim, 2005; Butcher et al., 2005; Wang et al., 2011 |
| CYP2D6 | Drug metabolism | *4 allele alters splicing, no enzyme activity | Marez et al., 1997; Kagimoto et al., 1990 |
| SCN1A | Drug target in epilepsy treatment | Splice isoforms have different sensitivity to phenytoin and lamotrigine | Thompson et al., 2011 |
| CAR | Nuclear receptor, xenobiotic sensing/processing | Alternate splicing alters ligands recognized by receptor | DeKeyser et al., 2011 |
| VEGF | Growth factor | Splice isoforms can have opposite effect | Harper and Bates, 2008 |
| BCL2L | Apoptosis regulator | Splice isoforms are anti- or pro-apoptotic | Bauman et al., 2010 |
| Disease-causing genes | |||
| MSTR1 | Oncogene | SSO can increase transcript length | Ghigna et al., 2010 |
| SMN | Spinal muscular atrophy | Exon 7 skipped. Multiple approaches for inclusion | Wirth et al., 2006; Vitte et al., 2007; Singh et al., 2009; Hua et al., 2010 |
| DMD | Duchenne muscular dystrophy | Exon 51 mutation and frameshift | van Deutekom et al., 2007, Goemans et al., 2011; Cirak et al., 2011 |
| IKBKAP | Familial dysautonomia | Phosphatidylserine and kinetin correct splicing defect | Keren et al., 2010; Axelrod et al., 2011; Shetty et al., 2011 |
| NF-1 | Neurofibromatosis | Kinetin corrects splicing defect | Pros et al., 2010 |