IthaID: 2096

Context nucleotide sequence:
GTAATTAACTGAACATATGGTTATT [C/T] ACAGTTTTTTCACAAGCAACCCTGC (Strand: +)

Also known as:

Comments: Associated with variation in HbF levels and F-cell numbers in healthy Northern Europeans (TwinsUK cohort). It strongly associated with HbF levels in the African American Cooperative Study of Sickle Cell Disease (CSSCD), in sickle cell disease (SCD) cohorts from Brazil, Cameroon and Tanzania, and in individuals from Thailand and China with β-thalassaemia and/or Hb E trait. Associated with increased HbF levels as well as clinical outcomes (acute chest syndrome and infection risk) and haematological parameters (total Hb levels and reticulocyte count) in pediatric patients with SCA from southeastern Brazil (n=240). Associated with HbF levels in Portuguese β-thal carriers. Associated with HbF levels in individuals from the SardiNIA study. It exhibited strong effect on the severity of the β-thalassaemia phenotype in Sardinian subjects. Associated with disease severity in Thai β0-thalassaemia/HbE patients. Associated with HbF levels in β-thalassaemia patients from Guangxi, Southern China. Associated with platelet and red blood cell counts in a Northern European cohort of healthy individuals. It significantly associated with fewer pain event in young patients with SCA (BABY HUG cohort) [PMID: 23606168]. Associated with a higher platelet count in the Kore Association Resource (KARE) project of the Korean Genome Epidemiology Study (KoGES; n=8842). The association was replicated in healthy samples from the Cardio Vascular Disease Association Study (CAVAS) of KoGES (n=3667) [PMID: 26064965]. The C allele associated with HbF in Kuwaiti patients with sickle cell disease. Found in almost complete LD with rs66650371 (3bp deletion) and rs35786788, conveying a strong association with high-HbF levels (>30%) [PMID: 34204365].

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Heterozygous records (preview in IthaPhen)

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12. Sheehan VA, Luo Z, Flanagan JM, Howard TA, Thompson BW, Wang WC, Kutlar A, Ware RE, , Genetic modifiers of sickle cell anemia in the BABY HUG cohort: influence on laboratory and clinical phenotypes., Am. J. Hematol. , 88(7), 571-6, 2013 PubMed
13. Wonkam A, Ngo Bitoungui VJ, Vorster AA, Ramesar R, Cooper RS, Tayo B, Lettre G, Ngogang J, Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon., PLoS ONE , 9(3), e92506, 2014 PubMed
14. Pakdee N, Yamsri S, Fucharoen G, Sanchaisuriya K, Pissard S, Fucharoen S, Variability of hemoglobin F expression in hemoglobin EE disease: hematological and molecular analysis., Blood Cells Mol. Dis. , 53(1), 11-5, 2014 PubMed
15. Mtatiro SN, Mgaya J, Singh T, Mariki H, Rooks H, Soka D, Mmbando B, Thein SL, Barrett JC, Makani J, Cox SE, Menzel S, Genetic association of fetal-hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer., BMC Med. Genet. , 16(0), 4, 2015 PubMed
16. Pereira C, Relvas L, Bento C, Abade A, Ribeiro ML, Manco L, Polymorphic variations influencing fetal hemoglobin levels: association study in beta-thalassemia carriers and in normal individuals of Portuguese origin., Blood Cells Mol. Dis. , 54(4), 315-20, 2015 PubMed
17. Danjou F, Zoledziewska M, Sidore C, Steri M, Busonero F, Maschio A, Mulas A, Perseu L, Barella S, Porcu E, Pistis G, Pitzalis M, Pala M, Menzel S, Metrustry S, Spector TD, Leoni L, Angius A, Uda M, Moi P, Thein SL, Galanello R, Abecasis GR, Schlessinger D, Sanna S, Cucca F, Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels., Nat. Genet. , 47(11), 1264-71, 2015 PubMed
18. Yi S, Lai Y, Zuo Y, Chen Y, Qin H, Wei Y, Yang Q, Lin L, Luo J, Fan X, Zheng C, Common genetic polymorphisms at three loci affect HbF levels in β-thalassemia patients from Southern China., Blood Cells Mol. Dis. , 62(0), 22-23, 2016 PubMed
19. Sales RR, Belisário AR, Faria G, Mendes F, Luizon MR, Viana MB, Functional polymorphisms of BCL11A and HBS1L-MYB genes affect both fetal hemoglobin level and clinical outcomes in a cohort of children with sickle cell anemia., Ann Hematol, 99(7), 1453-1463, 2020 PubMed
20. Akbulut-Jeradi N, Fernandez MJ, Al Khaldi R, Sukumaran J, Adekile A, Unique Polymorphisms at , and Loci Associated with HbF in Kuwaiti Patients with Sickle Cell Disease., J Pers Med, 11(6), , 2021 PubMed