+ Correspondence should be addressed to CAA (c.albers@gen.umcn.nl), WHO (who1000@cam.ac.uk) or AC (as889@cam.ac.uk) . Author Contributions: AC performed zebrafish knock down, analysis of zebrafish gene sequence; LHW, collected clinical cases with anti-Vel, performed confirmatory Sanger sequencing and phenotyping by flow cytometry and haem-agglutination; JCS performed confirmatory Sanger sequencing and analyzed the genotyping data; MK and PB analyzed the RNA-Sequencing data; PAS performed SMIM1 transfection experiments, MF and SF performed isolation of precursor cells; BS, GJ, AT and NG performed the analysis of the evolutionary conservation of the SMIM genes; AAS performed genotyping; EA, erythroblast culture and transfection; EB performed zebrafish knock down experiment with input from DS; HS, HHWS, VGH, NV performed cell culture experiments and performed EMSA's and transfection experiments and Q-PCR for SMIM1; RSNF, JK, HJW and LF performed eQTL and gene ontology analysis; AG, MN, JP, JGS, HLJ, KR, MdH were responsible for identification of Vel-negative and Vel-weak individuals by typing >360,000 samples; HHDK performed RNA-Seq with supervisory input from HGS who leads and coordinates the BluePrint epigenome project; GK supervised exome-sequencing; AR analysed expression data from whole genome expression arrays and RNAseq; HS expression data and vectors; DS iron homeostasis and other relevant laboratory measurements; D.St. oversaw zebrafish experiments. NS provided pre-publication access to red blood cell GWAS meta-analysis; PH eQTL analysis, expression data, SMIM1 vectors, pre-publication access to red blood cell GWAS meta-analysis; EvdS and WHO designed the study, CAA performed exome sequence analysis, Sanger sequence analysis, genetic analysis and statistical analysis; AC, LHW, EvdS, WHO and CAA wrote the paper.
