These authors contributed equally to this work.
Disruption of SMIM1 causes the Vel− blood type
Article first published online: 15 APR 2013
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 5, pages 751–761, May 2013
How to Cite
Ballif, B. A., Helias, V., Peyrard, T., Menanteau, C., Saison, C., Lucien, N., Bourgouin, S., Le Gall, M., Cartron, J.-P. and Arnaud, L. (2013), Disruption of SMIM1 causes the Vel− blood type. EMBO Mol Med, 5: 751–761. doi: 10.1002/emmm.201302466
- Issue published online: 7 MAY 2013
- Article first published online: 15 APR 2013
- Accepted manuscript online: 18 MAR 2013 03:10AM EST
- Manuscript Accepted: 10 MAR 2013
- Manuscript Revised: 5 MAR 2013
- Manuscript Received: 7 JAN 2013
- NIH. Grant Number: 8P20GM103449
- blood group;
- mass spectrometry;
- membrane protein;
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.