Table 2.
Polymorphisms of human sulfotransferases with potential clinical significance
| Gene | Reference SNP Cluster ID | Impact | Amino Acid Change | Location in Structure |
|---|---|---|---|---|
| SULT1A1 | rs1042008 | Increased risk of oral squamous cell carcinoma (Chung et al., 2009) | His149Tyr | Loop 2 |
| rs1801030 | Endometrial cancer (Rebbeck et al., 2006) | Met223Vala | Pre-loop 3 | |
| SULT1A2 | rs4987024 | Inversely associated with bladder cancer risk (Figueroa et al., 2008) | Tyr62PheTyr62Cys | Away from active site |
| SULT1B1 | rs11569729 | Higher odds ratio in glioblastoma gliomas (Kinnersley et al., 2016) | Thr261Met | Loop 3 |
| SULT1C4 | Rs1402467 | Increased relapse rate in acute myeloblastic leukemia (Monzo et al., 2006) | Asp5Glua | N-terminus not in structure |
| SULT1E1 | Increased risk of breast cancer (Cohen et al., 2009) | His224Gln | Pre-loop 3 | |
| SULT2B1 | rs140526640 | May relate to autosomal-recessive congenital ichthyosis (Youssefian et al., 2019) | Glu78Lysa | 5′PSB-loop helix Buried H-bond to Arg100 |
| rs1303127476 | May relate to autosomal-recessive congenital ichthyosis (Youssefian et al., 2019) | Arg100Trpa | Buried H-bond to Glu78 | |
| rs1114167424 | May cause autosomal-recessive congenital ichthyosis (Heinz et al., 2017) | Pro149Arg | 3′SB loop | |
| rs1052131 | Associated with esophageal squamous cell carcinoma risk (Hong et al., 2019) | Asp316Glu | C-terminus not ordered | |
| rs762765702 | May cause autosomal-recessive ichthyosis (Heinz et al., 2017) | Arg274Gln | Loop 3, binds 3′- phosphate of PAPS | |
| NDST1 | rs606231456 | Significant overlap in both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency (Najmabadi et al., 2011; Reuter et al., 2014) | Arg709Gln | On 3′SB helix |
| rs606231457 | Significant overlap in both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency (Reuter et al., 2014). | Glu642Asp | Catalytic base on Sweet Hill | |
| rs606231458 | Associated with intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency (Reuter et al., 2014) | Phe640Leu | On Sweet Hill | |
| rs606231459 | Associated with intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency (Reuter et al., 2014) | Gly611Ser | 5′PSB-loop | |
| HS2ST1b | rs758990524 | Associated with a syndromic phenotype comprising neurologic, skeletal, and renal abnormalities (Schneeberger et al., 2020) | Asp165Tyr | 3′SB loop |
| rs1651972168 | Associated with a syndromic phenotype comprising neurologic, skeletal, and renal abnormalities (Schneeberger et al., 2020) | Phe176Ser | 3′SB helix. Lines substrate binding pocket | |
| rs1651973144 | Associated with a syndromic phenotype comprising neurologic, skeletal, and renal abnormalities (Schneeberger et al., 2020). | Arg189Ser | Binds acceptor saccharide. Determinant residue for IdoA sulfation | |
| HS3ST3A1 | rs60532842 | Associated with P. falciparum parasitaemia (Atkinson et al., 2012) | Ala85Ser | N-terminal of sulfotransferase domain |
| HS3ST3B1c | rs9906590 | Associated with P. falciparum parasitaemia (Atkinson et al., 2012; Nguyen et al., 2018) | Glu363LysGlu363Gln | Away from active site |
| rs62056073 | Associated with P. falciparum parasitaemia (Atkinson et al., 2012; Nguyen et al., 2018) | Ile196ValIle196Phe | Away from active site | |
| rs62636623 | Associated with P. falciparum parasitaemia (Atkinson et al., 2012; Nguyen et al., 2018) | Gly83ArgGly83Trp | N-terminal of sulfotransferase domain | |
| HS6ST1d | rs780352591 | Found in hypogonadotropic hypogonadism patients (Tornberg et al., 2011) | Arg306Trp1 | Away from active site. |
| rs201307896 | Found in hypogonadotropic hypogonadism patients (Tornberg et al., 2011) | Arg306Glne | Away from active site | |
| rs761325768 | Found in hypogonadotropic hypogonadism patients (Tornberg et al., 2011) | Arg323Glne | Lines non-reducing end of substrate binding pocket | |
| rs199538589 | Found in hypogonadotropic hypogonadism patients (Tornberg et al., 2011; Cangiano et al., 2019; Choi et al., 2015) | Arg382Trpe | Extended C-terminal tail away from active site | |
| Found in hypogonadotropic hypogonadism patients (Tornberg et al., 2011) | Met404Vale | Extended C-terminal tail away from active site | ||
| HS6ST2d | rs866919041 | Associated with X-linked intellectual disability and severe myopia in two male twins (Paganini et al., 2019). | Gly306CysGly306Arg | Disordered loop away from active site |
List was obtained by utilizing the NSBI dbSNP search with clinical significance (likely pathogenic, pathogenic, and pathogenic likely pathogenic) and function class (missense).
anot found in NSBI dbSNP using listed criteria.
bHS2ST analysis based on crystal structure of chicken 2-OST PDB code 4NDZ.
cH3ST3B1 structural analysis based on structure of equivalent residue in H3ST3A1 PDB code 6XL8.
dHS6ST1 and HS6ST2 structural analysis based on crystal structure of zebrafish 6-OST-3 PDB id code 5T0A.
eNumbering of Arg306, Arg323, Arg382, and Met404 are listed as Arg296, Arg313, Arg372, and Met294 in Tornberg et al. (2011).