SLC4A1 solute carrier family 4 member 1 (Diego blood group) [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC4A1provided by HGNC
Official Full Name: solute carrier family 4 member 1 (Diego blood group)provided by HGNC
Primary source: HGNC:HGNC:11027
See related: Ensembl:ENSG00000004939 MIM:109270; AllianceGenome:HGNC:11027
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DI; FR; SW; WD; WR; AE1; CHC; SAO; WD1; BND3; EPB3; SPH4; CD233; EMPB3; RTA1A
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. [provided by RefSeq, Jul 2008]
Expression: Restricted expression toward bone marrow (RPKM 157.0) See more
Orthologs: mouse all
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Genomic context

Location:: 17q21.31

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (44248390..44268135, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (45101499..45121240, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (42325758..42345503, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO2 test be normal?
Title: Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO(2) test be normal?
Impaired trafficking and instability of mutant kidney anion exchanger 1 proteins associated with autosomal recessive distal renal tubular acidosis.
Title: Impaired trafficking and instability of mutant kidney anion exchanger 1 proteins associated with autosomal recessive distal renal tubular acidosis.
Identification of seven exonic variants in the SLC4A1, ATP6V1B1, and ATP6V0A4 genes that alter RNA splicing by minigene assay.
Title: Identification of seven exonic variants in the SLC4A1, ATP6V1B1, and ATP6V0A4 genes that alter RNA splicing by minigene assay.
Different Involvement of Band 3 in Red Cell Deformability and Osmotic Fragility-A Comparative GP.Mur Erythrocyte Study.
Title: Different Involvement of Band 3 in Red Cell Deformability and Osmotic Fragility-A Comparative GP.Mur Erythrocyte Study.
Clinical manifestation and phenotypic analysis of novel gene mutation in 28 Chinese children with hereditary spherocytosis.
Title: Clinical manifestation and phenotypic analysis of novel gene mutation in 28 Chinese children with hereditary spherocytosis.
Structural and functional insights into the mechanism of action of plant borate transporters.
Title: Structural and functional insights into the mechanism of action of plant borate transporters.
A clinical and experimental study of adult hereditary spherocytosis in the Chinese population.
Title: A clinical and experimental study of adult hereditary spherocytosis in the Chinese population.
Identification of a novel DI*02(2558T) allele associated with weakened expression of DI2 antigen.
Title: Identification of a novel DI*02(2558T) allele associated with weakened expression of DI2 antigen.
Genotypic analysis of SLC4A1 A858D mutation in Indian population associated with distal renal tubular Acidosis (dRTA) coupled with hemolytic anemia.
Title: Genotypic analysis of SLC4A1 A858D mutation in Indian population associated with distal renal tubular Acidosis (dRTA) coupled with hemolytic anemia.
Genome-Wide Association for HbA1c in Malay Identified Deletion on SLC4A1 that Influences HbA1c Independent of Glycemia.
Title: Genome-Wide Association for HbA1c in Malay Identified Deletion on SLC4A1 that Influences HbA1c Independent of Glycemia.

Submit: New GeneRIF Correction See all GeneRIFs (197)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant distal renal tubular acidosis MedGen: CN280572 OMIM: 179800 GeneReviews: Hereditary Distal Renal Tubular Acidosis	Compare labs
BLOOD GROUP--DIEGO SYSTEM MedGen: C1292286 OMIM: 110500 GeneReviews: Not available	Compare labs
BLOOD GROUP--FROESE MedGen: C1832168 OMIM: 601551 GeneReviews: Not available	Compare labs
BLOOD GROUP--SWANN SYSTEM MedGen: C1832169 OMIM: 601550 GeneReviews: Not available	Compare labs
BLOOD GROUP--WALDNER TYPE MedGen: C1862191 OMIM: 112010 GeneReviews: Not available	Compare labs
BLOOD GROUP--WRIGHT ANTIGEN MedGen: C1862190 OMIM: 112050 GeneReviews: Not available	Compare labs
Cryohydrocytosis MedGen: C1861453 OMIM: 185020 GeneReviews: Not available	Compare labs
Hereditary spherocytosis type 4 MedGen: C2675212 OMIM: 612653 GeneReviews: Not available	Compare labs
Malaria, susceptibility to MedGen: C1970028 OMIM: 611162 GeneReviews: Not available	Compare labs
Renal tubular acidosis, distal, 4, with hemolytic anemia MedGen: C5436235 OMIM: 611590 GeneReviews: Hereditary Distal Renal Tubular Acidosis	Compare labs
Southeast Asian ovalocytosis MedGen: C1862322 OMIM: 166900 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group; SLC4A1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH79167 (e-PCR)
- UniSTS:3588

RH46054 (e-PCR)
- UniSTS:48759

GDB:178577 (e-PCR)
- UniSTS:155029

RH70913 (e-PCR)
- UniSTS:74170

RH17959 (e-PCR)
- UniSTS:37053

RH67779 (e-PCR)
- UniSTS:52450

SLC4A1_726 (e-PCR)
- UniSTS:277747

WI-16724 (e-PCR)
- UniSTS:22518

Clone Names

MGC116750, MGC116753, MGC126619, MGC126623

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ankyrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables bicarbonate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables bicarbonate transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables chloride transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables chloride:bicarbonate antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables hemoglobin binding	IEA Inferred from Electronic Annotation more info
enables monoatomic anion transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein-membrane adaptor activity	TAS Traceable Author Statement more info	PubMed
enables solute:inorganic anion antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables solute:inorganic anion antiporter activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in bicarbonate transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in bicarbonate transport	IDA Inferred from Direct Assay more info	PubMed
involved_in bicarbonate transport	TAS Traceable Author Statement more info
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in chloride transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in erythrocyte development	IEA Inferred from Electronic Annotation more info
involved_in intracellular monoatomic ion homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in monoatomic anion transport	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of glycolytic process through fructose-6-phosphate	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of urine volume	IEA Inferred from Electronic Annotation more info
involved_in pH elevation	IEA Inferred from Electronic Annotation more info
involved_in plasma membrane phospholipid scrambling	IEA Inferred from Electronic Annotation more info
involved_in protein localization to plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in regulation of intracellular pH	IBA Inferred from Biological aspect of Ancestor more info
involved_in transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in Z disc	ISS Inferred from Sequence or Structural Similarity more info
part_of ankyrin-1 complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in blood microparticle	HDA more info	PubMed
located_in cortical cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: band 3 anion transport protein

Names: Diego blood group; Froese blood group; Swann blood group; Waldner blood group; Wright blood group; anion exchange protein 1; anion exchanger-1; band 3 anion exchanger; erythrocyte membrane protein band 3; erythroid anion exchange protein; solute carrier family 4 (anion exchanger), member 1 (Diego blood group); solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group); solute carrier family 4, anion exchanger, number 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007498.1 RefSeqGene

Range

5000..24745

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_803

mRNA and Protein(s)

NM_000342.4 → NP_000333.1 band 3 anion transport protein

See identical proteins and their annotated locations for NP_000333.1

Status: REVIEWED

Source sequence(s)

AC003043, AC003102, X12609

Consensus CDS

CCDS11481.1

UniProtKB/Swiss-Prot

G4V2I6, P02730, P78487, Q1ZZ45, Q4KKW9, Q4VB84, Q9UCY7, Q9UDJ1

UniProtKB/TrEMBL

E2RVJ0, G4V2I8

Related

ENSP00000262418.6, ENST00000262418.12

Conserved Domains (1) summary

TIGR00834
Location:58 → 910

ae; anion exchange protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

44248390..44268135 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011525129.3 → XP_011523431.1 band 3 anion transport protein isoform X1

UniProtKB/TrEMBL

E2RVJ0

Conserved Domains (3) summary

TIGR00834
Location:58 → 880

ae; anion exchange protein

pfam00955
Location:372 → 809

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:86 → 329

Band_3_cyto; Band 3 cytoplasmic domain
XM_005257593.6 → XP_005257650.1 band 3 anion transport protein isoform X3

See identical proteins and their annotated locations for XP_005257650.1

UniProtKB/TrEMBL

G4V2I8

Conserved Domains (3) summary

TIGR00834
Location:1 → 845

ae; anion exchange protein

pfam00955
Location:307 → 774

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:21 → 264

Band_3_cyto; Band 3 cytoplasmic domain
XM_011525130.2 → XP_011523432.1 band 3 anion transport protein isoform X2

UniProtKB/TrEMBL

E2RVJ0

Conserved Domains (2) summary

pfam00955
Location:372 → 770

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:86 → 329

Band_3_cyto; Band 3 cytoplasmic domain