Gene: SLC4A1

Alternate names for this Gene: AE1|BND3|CD233|CHC|DI|EMPB3|EPB3|FR|RTA1A|SAO|SPH4|SW|WD|WD1|WR

Gene Summary: The protein encoded by this gene is part of the anion exchanger (AE) family and is expressed in the erythrocyte plasma membrane, where it functions as a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs. The protein comprises two domains that are structurally and functionally distinct. The N-terminal 40kDa domain is located in the cytoplasm and acts as an attachment site for the red cell skeleton by binding ankyrin. The glycosylated C-terminal membrane-associated domain contains 12-14 membrane spanning segments and carries out the stilbene disulphonate-sensitive exchange transport of anions. The cytoplasmic tail at the extreme C-terminus of the membrane domain binds carbonic anhydrase II. The encoded protein associates with the red cell membrane protein glycophorin A and this association promotes the correct folding and translocation of the exchanger. This protein is predominantly dimeric but forms tetramers in the presence of ankyrin. Many mutations in this gene are known in man, and these mutations can lead to two types of disease: destabilization of red cell membrane leading to hereditary spherocytosis, and defective kidney acid secretion leading to distal renal tubular acidosis. Other mutations that do not give rise to disease result in novel blood group antigens, which form the Diego blood group system. Southeast Asian ovalocytosis (SAO, Melanesian ovalocytosis) results from the heterozygous presence of a deletion in the encoded protein and is common in areas where Plasmodium falciparum malaria is endemic. One null mutation in this gene is known, resulting in very severe anemia and nephrocalcinosis.

Gene is located in Chromosome: 17

Location in Chromosome : 17q21.31

Description of this Gene: solute carrier family 4 member 1 (Diego blood group)

Type of Gene: protein-coding

rs2072081 in SLC4A1 gene and Corpuscular Hemoglobin Concentration Mean PMID 23222517 2012 Seventy-five genetic loci influencing the human red blood cell.

rs2857078 in SLC4A1 gene and Finding of Mean Corpuscular Hemoglobin PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs5020 in SLC4A1 gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs5023 in SLC4A1 gene and Polysomnography PMID 23251661 2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.

rs863225461 in SLC4A1 gene and Pseudohyperkalemia Cardiff PMID 16227998 2005 Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1.

rs13306780 in SLC4A1 gene and RDW - Red blood cell distribution width result PMID 28957414 2017 Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs121912748 in SLC4A1 gene and RENAL TUBULAR ACIDOSIS, DISTAL, WITH HEMOLYTIC ANEMIA (disorder) PMID 9854053 1998 Novel AE1 mutations in recessive distal renal tubular acidosis. Loss-of-function is rescued by glycophorin A.

PMID 15211439 2004 Novel compound heterozygous SLC4A1 mutations in Thai patients with autosomal recessive distal renal tubular acidosis.

PMID 10926824 2000 Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells.

rs13306780 in SLC4A1 gene and Red cell distribution width determination PMID 28957414 2017 Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs1476512 in SLC4A1 gene and Reticulocyte count (procedure) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs5020 in SLC4A1 gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs121912741 in SLC4A1 gene and Spherocytosis, Type 4 PMID 16227998 2005 Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1.

PMID 8943874 1996 Characterization of 13 novel band 3 gene defects in hereditary spherocytosis with band 3 deficiency.

PMID 10580570 1999 Arginine 490 is a hot spot for mutation in the band 3 gene in hereditary spherocytosis.

PMID 10942416 2000 Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3.

PMID 11380459 2001 Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III.

PMID 8547122 1995 Band 3 Chur: a variant associated with band 3-deficient hereditary spherocytosis and substitution in a highly conserved position of transmembrane segment 11.

PMID 9207478 1997 Modulation of clinical expression and band 3 deficiency in hereditary spherocytosis.

PMID 9233560 1997 Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects.

PMID 10745622 2000 Characteristic features of the genotype and phenotype of hereditary spherocytosis in the Japanese population.

PMID 7530501 1995 Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis.

PMID 9973643 1998 Band 3 Tokyo: Thr837-->Ala837 substitution in erythrocyte band 3 protein associated with spherocytic hemolysis.

PMID 9012689 1997 Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism within the EPB3 locus.

PMID 1378323 1992 Band 3 Tuscaloosa: Pro327----Arg327 substitution in the cytoplasmic domain of erythrocyte band 3 protein associated with spherocytic hemolytic anemia and partial deficiency of protein 4.2.

PMID 8640229 1996 Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis.

PMID 15813913 2005 Band 3Tambaú: a de novo mutation in the AE1 gene associated with hereditary spherocytosis. Implications for anion exchange and insertion into the red blood cell membrane.

rs5020 in SLC4A1 gene and Triglycerides measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs13306775 in SLC4A1 gene and mathematical ability PMID 30038396 2018 Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.