Table 2 Summary of genes with SNPs significantly associated (p < 0.00001) with triptolide cytotoxicty in HapMAP LCLs

CFLAR

Caspase 8 and FADD-like apoptosis regulator

The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists

45

FAM126B

Family With Sequence Similarity 126, Member B

22

PPIL3

Peptidylprolyl isomerase 9cyclophilin)-like 3

This gene encodes a member of the cyclophilin family. Cyclophilins catalyze the cis-trans isomerization of peptidylprolyl imide bonds in oligopeptides. They have been proposed to act either as catalysts or as molecular chaperones in protein-folding events. Alternative splicing results in multiple transcript variants. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

7

ZNF532

2

NDUFB3

NADH dehydrogenase (ubiquinone0 1beta subcomplex,3, 12kD

This gene encodes an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I)which is the first enzyme in the electron transport chain of mitochondria. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. Mutations in this gene contribute to mitochondrial complex 1 deficiency

3

NIF3L1

NIF3 NGG1 interacting factor 3-like 1(S. cerevisiae)

Functions as transcriptional correpressor

11

ORC2

Origin recognition complex subunit 2

The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. This protein forms a core complex with ORC3,−4, and−5. It also interacts with CDC45 and MCM10, which are proteins known to be important for the initiation of DNA replication.

20

CLK1

CDC-like kinae 1

This gene encodes a member of the CDC2-like (or LAMMER) family of dual specificity protein kinases. In the nucleus, the encoded protein phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing, releasing them into the nucleoplasm. The choice of splice sites during pre-mRNA processing may be regulated by the concentration of transacting factors, including serine/arginine rich proteins. Therefore, the encoded protein may play an indirect role in governing splice site selection. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA

1

CSMD1

CUB and Sushi multiple domains 1

1

FNDC3B

fibronectin type III domain containing 3B

15

MTUS2

microtubule associated tumor suppressor candidate 2

Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules. May regulate the dynamics of microtubules at their growing distal tip

1

TP53BP2

tumor protein p53 binding protein, 2

This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. It is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family. It plays central role in regulation of apoptosis and cell growth via its interactions. Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. Inhibits the ability of APPBP1 to conjugate NEDD8 to CUL1, and thereby decreases APPBP1 ability to induce apoptosis. Impedes cell cycle progression at G2/M. Its apoptosis-stimulating activity is inhibited by its interaction with DDX42

1