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rs334

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 0 normal allele
(A;T) 4 carrier of, but unaffected by, sickle cell anemia; greater malaria resistance
(AG;AG) 0 common in clinvar
(T;T) 5 sickle cell anemia
ReferenceGRCh38 38.1/141
Chromosome11
Position5227002
GeneHBB
is asnp
is mentioned by
dbSNPrs334
ebirs334
HLIrs334
Exacrs334
Varsomers334
Maprs334
PheGenIrs334
hapmaprs334
1000 genomesrs334
hgdprs334
ensemblrs334
gopubmedrs334
geneviewrs334
scholarrs334
googlers334
pharmgkbrs334
gwascentralrs334
openSNPrs334
23andMers334
23andMe allrs334
SNP Nexus

SNPshotrs334
SNPdbers334
MSV3drs334
GWAS Ctlgrs334
Merged fromRs77121243
GMAF0.0225
Max Magnitude5
? (A;A) (A;T) (T;T) 28

This position causes sickle cell anemia

It is an ambiguous flip and is very prone to confusion

dbSNP uses the minus orientation

  • rs334(A) encodes the normal Hb A form of (adult) hemoglobin.
  • rs334(T) encodes the sickling form of hemoglobin, Hb S.

23andMe tests this snp under the name i3003137 on the plus orientation

  • i3003137(T) encodes the normal Hb A form of (adult) hemoglobin.
  • i3003137(A) encodes the sickling form of hemoglobin, Hb S.

Note that the 1000 genomes project is also reporting this in the plus orientation.

gs228 and gs229 cover these arguably better

Only individuals homozygous for this allele, in other words having the rs334(T;T) genotype, will have sickle cell anemia. The (T) allele appears to have maintained through evolution due to the ~10 fold higher resistance to life-threatening forms of malaria that heterozygotes (rs334(A;T) genotypes) exhibit.

See the SNPedia sickle cell anemia entry for more information.


[PMID 20128890OA-icon.png] Loss of balancing selection in the betaS globin locus

[PMID 20552021OA-icon.png] Haptoglobin and sickle cell polymorphisms and risk of active trachoma in gambian children

OMIM141900
Desc
Variant0039
Relatedalso
OMIM141900
Desc
Variant0040
Relatedalso
OMIM141900
Desc
Variant0085
Relatedalso
OMIM141900
Desc
Variant0243
Relatedalso
OMIM141900
Desc
Variant0244
Relatedalso
OMIM141900
Desc
Variant0245
Relatedalso
OMIM141900
Desc
Variant0246
Relatedalso
OMIM141900
Desc
Variant0247
Relatedalso
OMIM141900
Desc
Variant0521
Relatedalso
OMIM141900
Desc
Variant0523
Relatedalso
[PMID 16637741OA-icon.png] Seasonal Childhood Anaemia in West Africa Is Associated with the Haptoglobin 2-2 Genotype

[PMID 22506028OA-icon.png] Haplotype Analyses of Haemoglobin C and Haemoglobin S and the Dynamics of the Evolutionary Response to Malaria in Kassena-Nankana District of Ghana

[PMID 22574149OA-icon.png] Underlying Factors Associated with Anemia in Amazonian Children: A Population-Based, Cross-Sectional Study

ClinVar
Risk rs334(C,G,T;C,G,T)
Alt rs334(C,G,T;C,G,T)
Reference rs334(A;A)
Significance Other
Disease HEMOGLOBIN ZIGUINCHOR HEMOGLOBIN S Hb SS disease Malaria HEMOGLOBIN S (ANTILLES) Sickle cell-Hemoglobin O Arab disease HEMOGLOBIN S (PROVIDENCE) HEMOGLOBIN S (TRAVIS) HEMOGLOBIN S (CAMEROON) HEMOGLOBIN JAMAICA PLAIN not provided HEMOGLOBIN G (MAKASSAR)
Variation info
Gene HBB
CLNDBN HEMOGLOBIN ZIGUINCHOR HEMOGLOBIN S Hb SS disease Malaria, resistance to HEMOGLOBIN S (ANTILLES) Sickle cell-Hemoglobin O Arab disease HEMOGLOBIN S (PROVIDENCE) HEMOGLOBIN S (TRAVIS) HEMOGLOBIN S (CAMEROON) HEMOGLOBIN JAMAICA PLAIN not provided HEMOGLOBIN G (MAKASSAR)
Reversed 1
HGVS NC_000011.9:g.5248232T>A; NC_000011.9:g.5248232T>G
CLNSRC OMIM Allelic Variant HBVAR
CLNACC RCV000016286.3, RCV000016573.8, RCV000016574.27, RCV000016575.30, RCV000016576.5, RCV000016577.5, RCV000016579.5, RCV000016580.5, RCV000016877.5, RCV000016879.2, RCV000030905.3, RCV000224000.1, RCV000016352.2,


[PMID 17668374OA-icon.png] Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.


[PMID 17688704OA-icon.png] Classical sickle beta-globin haplotypes exhibit a high degree of long-range haplotype similarity in African and Afro-Caribbean populations.


[PMID 19145247OA-icon.png] Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three African populations.


[PMID 19281305OA-icon.png] Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.


[PMID 20226094OA-icon.png] Myosin individualized: single nucleotide polymorphisms in energy transduction.


[PMID 20585394OA-icon.png] Transforming growth factor beta 2 and heme oxygenase 1 genes are risk factors for the cerebral malaria syndrome in Angolan children.

GET Evidence
HBB-E7V
aa_change Glu7Val
aa_change_short E7V
impact pathogenic
qualified_impact High clinical importance, pathogenic
overall_frequency 0.0140361
summary HB-S variant responsible for causing Sickle Cell Disease when homozygous (residue count follows p.HBB). This is often also referred to as E6V, referring to the position of the amino acid in the final protein product (the first amino acid is removed after translation). Heterozygotes have Sickle Cell Trait.


[PMID 5509617] Hemoglobin G Makassar: beta-6 Glu leads to Ala.


[PMID 12403489] Hb G-Makassar [beta6(A3)Glu-->Ala; codon 6 (GAG-->GCG)]: molecular characterization, clinical, and hematological effects.