Disruption of SMIM1 causes the Vel− blood type
peer-reviewed · EMBO Molecular Medicine · 2013
| Date | 2013-05-01 |
| Type | peer-reviewed |
| Venue | EMBO Molecular Medicine |
| Publisher | Springer Science and Business Media LLC |
| Contribution | downstream-application |
| DOI | 10.1002/emmm.201302466 |
| Citations (OpenAlex) | 50 |
Abstract
Here, we report the biochemical and genetic basis of the Vel blood group antigen, which has been a vexing mystery for decades, especially as anti-Vel regularly causes severe haemolytic transfusion reactions. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel- cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. A cohort of 70 Vel- individuals was found to be uniformly homozygous for a 17 nucleotide deletion in the coding sequence of SMIM1. The genetic homogeneity of the Vel- blood type, likely having a common origin, facilitated the development of two highly specific DNA-based tests for rapid Vel genotyping, which can be easily integrated into blood group genotyping platforms. These results answer a 60-year-old riddle and provide tools of immediate assistance to all clinicians involved in the care of Vel- patients.
Methods and tools
- Vel blood group antigen identification (SMIM1): De novo peptide sequencing of the protein purified from red blood cell membranes identified the long-sought Vel blood group antigen carrier as SMIM1, later confirmed genetically.