Novel HMBS mutants that cause AIP, and putative genetic modifiers of porphyria
| Novel HMBS mutants . | Putative genetic modifiers of porphyria . | ||
|---|---|---|---|
| Mutation type . | Variant . | Classification . | Name . |
| Deletion | c.6delA | Serum porphyrin transporters | Albumin |
| c.657_658delCT | Haptoglobin | ||
| Hemopexin | |||
| High/low-density lipoproteins | |||
| Insertion | c.741-748dupCATCGCTG | Porphyrin transporters | FLVCR1a/b |
| BCRP/ABCG2 | |||
| ABCB6 | |||
| Substitution | c.93C>T | Cellular porphyrin binding proteins | Glutathione S-transferase |
| c.763G>T | Liver fatty acid binding protein | ||
| c.4219T>G | Heme binding protein 23 | ||
| c.5387C>T | p22HBP | ||
| p.H305N (c.1070C>A) | GAPDH | ||
| p.R321L (c.1119G>T, c.1120T>A) | |||
| Splicing | c.651+2A>G | Porphyrin biosynthesis modulators | CLPX |
| IVS3-1G>C | β-catenin | ||
| GATA-1 | |||
| Novel HMBS mutants . | Putative genetic modifiers of porphyria . | ||
|---|---|---|---|
| Mutation type . | Variant . | Classification . | Name . |
| Deletion | c.6delA | Serum porphyrin transporters | Albumin |
| c.657_658delCT | Haptoglobin | ||
| Hemopexin | |||
| High/low-density lipoproteins | |||
| Insertion | c.741-748dupCATCGCTG | Porphyrin transporters | FLVCR1a/b |
| BCRP/ABCG2 | |||
| ABCB6 | |||
| Substitution | c.93C>T | Cellular porphyrin binding proteins | Glutathione S-transferase |
| c.763G>T | Liver fatty acid binding protein | ||
| c.4219T>G | Heme binding protein 23 | ||
| c.5387C>T | p22HBP | ||
| p.H305N (c.1070C>A) | GAPDH | ||
| p.R321L (c.1119G>T, c.1120T>A) | |||
| Splicing | c.651+2A>G | Porphyrin biosynthesis modulators | CLPX |
| IVS3-1G>C | β-catenin | ||
| GATA-1 | |||
Novel HMBS mutants as identified by comparing the AIP mutants described in supplemental Table 2 with the data for HMBS in the gnomAD database and National Center for Biotechnology Information database. The listed variants are included as reported in the citations in supplemental Table 2. Putative reported genetic modifiers of porphyria, based on the ability of these proteins to bind porphyrins or modulate porphyrin biosynthesis directly or indirectly. For details and primary citations, see reference 3.
ABCB6, adenosine triphosphate-binding cassette subfamily B member 6; ABCG2, adenosine triphosphate-binding cassette subfamily G member 2; BCRP, breast cancer resistance protein; CLPX, adenosine triphosphate-dependent Clp protease adenosine triphosphate-binding subunit clpX-like; FLVCR1a/b, feline leukemia virus subgroup C receptor-related protein 1a/b; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GATA-1, GATA-binding factor 1; p22HBP, 22-kDa heme-binding protein.