IthaID: 3120



Names and Sequences

Functionality: Disease modifying mutation
Common Name:  rs1799945 HGVS Name: NG_008720.2:g.8671C>G

Context nucleotide sequence:
TGACCAGCTGTTCGTGTTCTATGAT [C/G] ATGAGAGTCGCCGTGTGGAGCCCCG (Strand: +)

Protein sequence:
MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDDESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPSPSGTLVIGVISGIAVFVVILFIGILFIILRKRQGSRGAMGHYVLAERE

Comments: The H63D mutation is implicated in hereditary hemochromatosis. Studies investigating the effect of H63D homozygosity or even heterozygosity on iron overload in patients with β-thalassaemia reported conflicting findings. Serum iron and transferrin saturation levels were significantly higher in β-thalassaemia carriers of southern Portugal origin heterozygous for the H63D polymorphism [PMID: 15538648]. Homozygosity for the H63D mutation associated with higher ferritin levels in β-thalassaemia patients or carriers from Egypt [PMID: 27335591] and Sardinia [PMID: 11869934], suggesting a modulating effect on iron load. No effect on cardiac iron overload but significant association with higher pulmonary vein atrial reversal flow velocity, which informs about diastolic dysfunction during cardiac follow-up, in Turkish β-thalassaemia major patients [PMID: 24087894]. The presence of H63D does not cause increased serum ferritin levels in β-thalassaemia minor patients from Iran [PMID: 14703689], India [PMID: 27561698, 15777346], or the Balearic Islands [PMID: 22122796]. No significant difference in terms of ferritin levels or thalassaemia-related complications between β-thalassaemia major patients with or without this variant from Italy [PMID: 19734422, 9858237, 10477452], Iran [PMID: 31205627] and Tunisia [PMID: 17303462].

External Links

Location

Chromosome: 6
Locus: NG_008720.2
Locus Location: 8671
Size: 1 bp
Located at: HFE
Specific Location: Exon 2

Phenotype

Allele Phenotype (Cis):N/A
Allele Phenotype (Trans):N/A
Associated Phenotypes: Increased serum iron [HP:0003452]
Elevated transferrin saturation [HP:0012463]
Increased serum ferritin [HP:0003281]

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: Missense codons (Protein Structure)
Ethnic Origin: Egyptian, Turkish, Sardinian, Indian, Portuguese
Inheritance: Quantitative trait
DNA Sequence Determined: Yes
Detection Methods: Direct DNA sequencing

Sequence Viewer

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Publications / Origin

  1. Borgna-Pignatti C, Solinas A, Bombieri C, Micciolo R, Gamberini MR, De Stefano P, De Menis E, Pignatti PF, The haemochromatosis mutations do not modify the clinical picture of thalassaemia major in patients regularly transfused and chelated., Br. J. Haematol., 103(3), 813-6, 1998 PubMed
  2. Longo F, Zecchina G, Sbaiz L, Fischer R, Piga A, Camaschella C, The influence of hemochromatosis mutations on iron overload of thalassemia major., Haematologica, 84(9), 799-803, 1999 PubMed
  3. Melis MA, Cau M, Deidda F, Barella S, Cao A, Galanello R, H63D mutation in the HFE gene increases iron overload in beta-thalassemia carriers., Haematologica, 87(3), 242-5, 2002 PubMed
  4. Melis MA, Cau M, Congiu R, Ruvoletto L, Cao A, Galanello R, Frequency of hemochromatosis C282Y and H63D mutations in Sardinia., Genet. Test., 6(4), 327-9, 2002 PubMed
  5. Jazayeri M, Bakayev V, Adibi P, Haghighi Rad F, Zakeri H, Kalantar E, Zali MR, Frequency of HFE gene mutations in Iranian beta-thalassaemia minor patients., European journal of haematology, 71(6), 408-11, 2003 PubMed
  6. Martins R, Picanço I, Fonseca A, Ferreira L, Rodrigues O, Coelho M, Seixas T, Miranda A, Nunes B, Costa L, Romão L, Faustino P, The role of HFE mutations on iron metabolism in beta-thalassemia carriers., J. Hum. Genet., 49(12), 651-5, 2004 PubMed
  7. Garewal G, Das R, Ahluwalia J, Marwaha RK, Prevalence of the H63D mutation of the HFE in north India: its presence does not cause iron overload in beta thalassemia trait., Eur. J. Haematol., 74(4), 333-6, 2005 PubMed
  8. Mellouli F, El Borgi W, Kaabi H, Ben Hassen E, Sassi R, Hmida H, Cherif G, Maamar M, Zouari B, Boukef K, Bejaoui M, Hmida S, [HFE gene mutations in Tunisian major beta-Thalassemia and iron overload]., Transfus Clin Biol, 13(6), 353-7, 2006 PubMed
  9. Sharma V, Panigrahi I, Dutta P, Tyagi S, Choudhry VP, Saxena R, HFE mutation H63D predicts risk of iron over load in thalassemia intermedia irrespective of blood transfusions., Indian J Pathol Microbiol, 50(1), 82-5, 2007 PubMed
  10. Andreani M, Radio FC, Testi M, De Bernardo C, Troiano M, Majore S, Bertucci P, Polchi P, Rosati R, Grammatico P, Association of hepcidin promoter c.-582 A>G variant and iron overload in thalassemia major., Haematologica, 94(9), 1293-6, 2009 PubMed
  11. López-Escribano H, Ferragut JF, Parera MM, Guix P, Castro JA, Ramon MM, Picornell A, Effect of co-inheritance of β-thalassemia and hemochromatosis mutations on iron overload., Hemoglobin, 36(1), 85-92, 2012 PubMed
  12. Turedi A, Oymak Y, Meşe T, Yaman Y, Bayraktaroglu S, Alpman A, Ozkinay F, Aydınok Y, Vergin C, The effect of HFE polymorphisms on cardiac iron overload in patients with beta-thalassemia major., Pediatr Hematol Oncol , 30(8), 755-60, 2013 PubMed
  13. Enein AA, El Dessouky NA, Mohamed KS, Botros SK, Abd El Gawad MF, Hamdy M, Dyaa N, Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload., Open Access Maced J Med Sci , 4(2), 226-31, 2016 PubMed
  14. Nadkarni AH, Singh AA, Colaco S, Hariharan P, Colah RB, Ghosh K, Effect of the Hemochromatosis Mutations on Iron Overload among the Indian β Thalassemia Carriers., J. Clin. Lab. Anal., 31(3), , 2017 PubMed
  15. Fekri K, Asle Rasouli N, Tavallai Zavareh SA, Jalil M, Moradi F, Hosseinpour M, Teimori H, Hepcidin and Polymorphisms and Ferritin Level in β-Thalassemia Major., Int J Hematol Oncol Stem Cell Res, 13(1), 42-48, 2019 PubMed
Created on 2016-10-06 11:43:53, Last reviewed on 2019-07-04 12:45:40 (Show full history)

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