{{Rsnum
|rsid=334
|Gene=HBB
|Chromosome=11
|position=5227002
|Orientation=minus
|ReferenceAllele=A
|MissenseAllele=T
|GMAF=0.0225
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;T)
|geno3=(T;T)
|Gene_s=HBB
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;T)
| geno3=(T;T)
| CEU | 100.0 | 0.0 | 0.0
| HCB | 100.0 | 0.0 | 0.0
| JPT | 100.0 | 0.0 | 0.0
| YRI | 76.7 | 23.3 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 100.0 | 0.0 | 0.0
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=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 [http://browser.1000genomes.org/Homo_sapiens/Variation/Summary?r=11:5247732-5248732;v=rs334;vdb=variation;vf=4 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 Auto
|PMID=20128890
|Title=Loss of balancing selection in the betaS globin locus
|OA=1
}}
{{PMID Auto
|PMID=20552021
|Title=Haptoglobin and sickle cell polymorphisms and risk of active trachoma in gambian children
|OA=1
}}
{{omim
|id=141900
|rsnum=334
|variant=0039
}}
{{omim
|id=141900
|rsnum=334
|variant=0040
}}
{{omim
|id=141900
|rsnum=334
|variant=0085
}}
{{omim
|id=141900
|rsnum=334
|variant=0243
}}
{{omim
|id=141900
|rsnum=334
|variant=0244
}}
{{omim
|id=141900
|rsnum=334
|variant=0245
}}
{{omim
|id=141900
|rsnum=334
|variant=0246
}}
{{omim
|id=141900
|rsnum=334
|variant=0247
}}
{{omim
|id=141900
|rsnum=334
|variant=0521
}}
{{omim
|id=141900
|rsnum=334
|variant=0523
}}
{{PMID Auto
|PMID=16637741
|Title=Seasonal Childhood Anaemia in West Africa Is Associated with the Haptoglobin 2-2 Genotype
|OA=1
}}
{{PMID Auto
|PMID=22506028
|Title=Haplotype Analyses of Haemoglobin C and Haemoglobin S and the Dynamics of the Evolutionary Response to Malaria in Kassena-Nankana District of Ghana
|OA=1
}}
{{PMID Auto
|PMID=22574149
|Title=Underlying Factors Associated with Anemia in Amazonian Children: A Population-Based, Cross-Sectional Study
|OA=1
}}{{ClinVar
|rsid=334
|Reversed=1
|FwdREF=A
|FwdALT=C,G,T
|REF=T
|ALT=A,C,G
|RSPOS=5248232
|CHROM=11
|dbSNPBuildID=36
|SSR=0
|SAO=1
|VP=0x050368000000150517110104
|GENEINFO=HBB:3043
|GENE_NAME=HBB
|GENE_ID=3043
|WGT=0
|VC=SNV
|CLNALLE=1; 3
|CLNHGVS=NC_000011.9:g.5248232T>A; NC_000011.9:g.5248232T>G
|CLNORIGIN=1
|CLNSRCID=
GTR000115629; GTR000500319; 141900.0039; 141900.0040; 141900.0243; 141900.0244; 141900.0245; 141900.0246; 141900.0247; 141900.0521; 141900.0523; 228; 141900.0085
|CLNSIG=255
|CLNCUI=
|CLNACC=
RCV000016286.1; RCV000016573.1; RCV000016574.21; RCV000016575.24; RCV000016576.1; RCV000016577.1; RCV000016579.1; RCV000016580.1; RCV000016877.1; RCV000016879.1; RCV000030905.1; RCV000016352.1
|Tags=RV;PM;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;PH3;LSD;OM;NOV
|CAF=0.9775; 0.0225; .
|CLNDBN=HEMOGLOBIN ZIGUINCHOR; HEMOGLOBIN S; Hb SS disease; Malaria, resistance to; HEMOGLOBIN S (ANTILLES); HEMOGLOBIN S (OMAN); HEMOGLOBIN S (PROVIDENCE); HEMOGLOBIN S (TRAVIS); HEMOGLOBIN S (CAMEROON); HEMOGLOBIN JAMAICA PLAIN; HEMOGLOBIN G (MAKASSAR)
|CLNDSDB=GeneReviews:MedGen:OMIM:Orphanet:SNOMED_CT; MedGen
|CLNDSDBID=NBK1377:C0002895:603903:232:127040003; C2720293
|CLNSRC=GTR; OMIM Allelic Variant; HBVAR
|COMMON=1
|Disease=HEMOGLOBIN ZIGUINCHOR; HEMOGLOBIN S; Hb SS disease; Malaria; HEMOGLOBIN S (ANTILLES); HEMOGLOBIN S (OMAN); HEMOGLOBIN S (PROVIDENCE); HEMOGLOBIN S (TRAVIS); HEMOGLOBIN S (CAMEROON); HEMOGLOBIN JAMAICA PLAIN; HEMOGLOBIN G (MAKASSAR)
}}{{PMID Auto
|PMID=17668374
|Title=Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
|OA=1
}}

{{PMID Auto
|PMID=17688704
|Title=Classical sickle beta-globin haplotypes exhibit a high degree of long-range haplotype similarity in African and Afro-Caribbean populations.
|OA=1
}}

{{PMID Auto
|PMID=19145247
|Title=Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three African populations.
|OA=1
}}

{{PMID Auto
|PMID=19281305
|Title=Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.
|OA=1
}}

{{PMID Auto
|PMID=20226094
|Title=Myosin individualized: single nucleotide polymorphisms in energy transduction.
|OA=1
}}

{{PMID Auto
|PMID=20585394
|Title=Transforming growth factor beta 2 and heme oxygenase 1 genes are risk factors for the cerebral malaria syndrome in Angolan children.
|OA=1
}}{{GET Evidence
|gene=HBB
|aa_change=Glu7Val
|aa_change_short=E7V
|impact=pathogenic
|qualified_impact=High clinical importance,  pathogenic
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs334
|overall_frequency_n=151
|overall_frequency_d=10758
|overall_frequency=0.0140361
|n_genomes=6
|n_genomes_annotated=0
|n_haplomes=6
|n_articles=11
|n_articles_annotated=11
|qualityscore_in_silico=5
|qualitycomment_in_silico=Y
|qualityscore_in_vitro=5
|qualitycomment_in_vitro=Y
|qualityscore_case_control=5
|qualitycomment_case_control=Y
|qualityscore_familial=5
|qualitycomment_familial=Y
|qualityscore_severity=4
|qualitycomment_severity=Y
|qualityscore_treatability=4
|qualitycomment_treatability=Y
|gene_in_genetests=Y
|pph2_score=0.016
|genetests_testable=Y
|genetests_reviewed=Y
|nblosum100=5
|autoscore=3
|n_web_uneval=9
|variant_evidence=2
|clinical_importance=2
|summary_short=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 Auto
|PMID=5509617
|Title=Hemoglobin G Makassar: beta-6 Glu leads to Ala.
}}

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