IthaID: 2132
Names and Sequences
| Functionality: | Disease modifying mutation | Pathogenicity: | N/A |
|---|---|---|---|
| Common Name: | CD 325 GAG>AAG [Glu>Lys] | HGVS Name: | NG_013087.1:g.7203G>A |
Context nucleotide sequence:
GCGGCTGGAGATTCGCGCGCTCGGAC [G/A] AGCTGACCCGCCACTACCGGAAACA (Strand: -)
Protein sequence:
MATAETALPSISTLTALGPFPDTQDDFLKWWRSEEAQDMGPGPPDPTEPPLHVKSEDQPGEEEDDERGADATWDLDLLLTNFSGPEPGGAPQTCALAPSEASGAQYPPPPETLGAYAGGPGLVAGLLGSEDHSGWVRPALRARAPDAFVGPALAPAPAPEPKALALQPVYPGPGAGSSGGYFPRTGLSVPAASGAPYGLLSGYPAMYPAPQYQGHFQLFRGLQGPAPGPATSPSFLSCLGPGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAHTCAHPGCGKSYTKSSHLKAHLRTHTGEKPYACTWEGCGWRFARSDKLTRHYRKHTGQRPFRCQLCPRAFSRSDHLALHMKRHL
Also known as: E325K
Comments: Found in a heterozygous state in patients with congenital dyserythropoietic anaemia. It has a dominant-negative effect on the transcriptional activity of KLF1. It is located in the second zinc finger, affecting KLF1 binding to its cognate DNA motif, thus leading to a profound dysregulation of globin gene expression. Associates with high levels of HbF. Abolishes the expression of the water channel AQP1 and the adhesion molecule CD44 on erythrocytes.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Allele Phenotype (Cis): | Unknown for KLF1 |
|---|---|
| Allele Phenotype (Trans): | Increased expression for Aγ or Gγ |
| Associated Phenotypes: | Hb F levels [HP:0011904] [OMIM:141749] |
Location
| Chromosome: | 19 |
|---|---|
| Locus: | NG_013087.1 |
| Locus Location: | 7203 |
| Size: | 1 bp |
| Located at: | KLF1 |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Taiwanese |
| Molecular mechanism: | N/A |
| Inheritance: | Quantitative trait |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Wickramasinghe SN, Illum N, Wimberley PD, Congenital dyserythropoietic anaemia with novel intra-erythroblastic and intra-erythrocytic inclusions., Br. J. Haematol. , 79(2), 322-30, 1991
- Arnaud L, Saison C, Helias V, Lucien N, Steschenko D, Giarratana MC, Prehu C, Foliguet B, Montout L, de Brevern AG, Francina A, Ripoche P, Fenneteau O, Da Costa L, Peyrard T, Coghlan G, Illum N, Birgens H, Tamary H, Iolascon A, Delaunay J, Tchernia G, Cartron JP, A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia., Am. J. Hum. Genet. , 87(5), 721-7, 2010
- Singleton BK, Lau W, Fairweather VS, Burton NM, Wilson MC, Parsons SF, Richardson BM, Trakarnsanga K, Brady RL, Anstee DJ, Frayne J, Mutations in the second zinc finger of human EKLF reduce promoter affinity but give rise to benign and disease phenotypes., Blood , 118(11), 3137-45, 2011
- Jaffray JA, Mitchell WB, Gnanapragasam MN, Seshan SV, Guo X, Westhoff CM, Bieker JJ, Manwani D, Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: review of all reported cases and development of a clinical diagnostic paradigm., Blood Cells Mol. Dis. , 51(2), 71-5, 2013