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    SLC9B2 solute carrier family 9 member B2 [ Homo sapiens (human) ]

    Gene ID: 133308, updated on 9-Dec-2024

    Summary

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    Official Symbol
    SLC9B2provided by HGNC
    Official Full Name
    solute carrier family 9 member B2provided by HGNC
    Primary source
    HGNC:HGNC:25143
    See related
    Ensembl:ENSG00000164038 MIM:611789; AllianceGenome:HGNC:25143
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NHA2; NHE10; NHEDC2
    Summary
    Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]
    Expression
    Broad expression in brain (RPKM 4.9), liver (RPKM 4.7) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SLC9B2 in Genome Data Viewer
    Location:
    4q24
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (103018029..103077319, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (106329916..106389210, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (103939186..103998476, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 9 member B1 Neighboring gene poly(A) binding protein cytoplasmic 1 pseudogene 7 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:103859100-103859749 Neighboring gene ACTR3B pseudogene 4 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:103940703-103941203 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15604 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21763 Neighboring gene 3-hydroxybutyrate dehydrogenase 2 Neighboring gene centromere protein E Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:104119362-104119916

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Allosteric links between the hydrophilic N-terminus and transmembrane core of human Na(+) /H(+) antiporter NHA2. Velázquez D, et al. Protein Sci, 2022 Dec. PMID 36177733, Free PMC Article
    2. Mutational analysis of NHAoc/NHA2 in Saccharomyces cerevisiae. Huang X, et al. Biochim Biophys Acta, 2010 Dec. PMID 20713131, Free PMC Article
    3. Model-guided mutagenesis drives functional studies of human NHA2, implicated in hypertension. Schushan M, et al. J Mol Biol, 2010 Mar 12. PMID 20053353, Free PMC Article
    4. Proteomic profile of osteoclast membrane proteins: identification of Na+/H+ exchanger domain containing 2 and its role in osteoclast fusion. Ha BG, et al. Proteomics, 2008 Jul. PMID 18600791
    5. NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts. Battaglino RA, et al. Bone, 2008 Jan. PMID 17988971, Free PMC Article

    See all (17) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Allosteric links between the hydrophilic N-terminus and transmembrane core of human Na[+] /H[+] antiporter NHA2.
      Title: Allosteric links between the hydrophilic N-terminus and transmembrane core of human Na(+) /H(+) antiporter NHA2.
    2. The exchange activity of NHA2 (SLC9B2) is electroneutral, despite harboring the 2 conserved aspartic acid residues found in NapA and other bacterial homologues. The equivalent residue to K305 in human NHA2 has been replaced with arginine, which is a mutation that makes NapA electroneutral. A transmembrane embedded lysine residue is essential for electrogenic transport in Na(+)/H(+) antiporters.
      Title: Dissecting the proton transport pathway in electrogenic Na(+)/H(+) antiporters.
    3. the ubiquitous tissue distribution of NHA2 suggests that H(+)-coupled transport is more widespread. The coexistence of Na(+) and H(+)-driven chemiosmotic circuits has implications for salt and pH regulation in the kidney.
      Title: Unconventional chemiosmotic coupling of NHA2, a mammalian Na+/H+ antiporter, to a plasma membrane H+ gradient.
    4. mutation in AA residues V161 and F357 reduced ability of transfected BW31a cells to remove intracellular Na and grow in NaCl-medium; yeast expressing F357 F437 cannot grow in 0.4M NaCl, suggesting these residues also essential for antiporter activity
      Title: Mutational analysis of NHAoc/NHA2 in Saccharomyces cerevisiae.
    5. Observational study of gene-disease association. (HuGE Navigator)
      Title: A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts.
    6. cluster of essential, highly conserved titratable residues located in an assembly region made of two discontinuous helices of inverted topology, each interrupted by an extended chain
      Title: Model-guided mutagenesis drives functional studies of human NHA2, implicated in hypertension.
    7. restricted to the distal convoluted tubule in the kidney
      Title: Characterization of the sodium/hydrogen exchanger NHA2.
    8. Na+/H+ antiporter genes may contribute to sodium-lithium countertransport activity and salt homeostasis in humans[NHA1 and NHA2]
      Title: A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension.
    9. NHA-oc/NHA2 displays the expected activities of a bona fide cation-proton antiporter and plays a key role(s) in normal osteoclast differentiation and function
      Title: NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts.
    Submit: New GeneRIF Correction

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ23984

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables lithium:proton antiporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables lithium:proton antiporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sodium:proton antiporter activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables sodium:proton antiporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sodium:proton antiporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in clathrin-dependent endocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in flagellated sperm motility ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in inorganic cation transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in lithium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in monoatomic ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in positive regulation of osteoclast development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proton transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of insulin secretion involved in cellular response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in sodium ion homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sodium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in sodium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in basolateral plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in recycling endosome ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in recycling endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in sperm principal piece ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in synaptic vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    sodium/hydrogen exchanger 9B2
    Names
    NHE domain-containing protein 2
    Na(+)/H(+) exchanger NHA2
    Na(+)/H(+) exchanger-like domain-containing protein 2
    Na+/H+ exchanger domain containing 2
    mitochondrial Na(+)/H(+) exchanger NHA2
    mitochondrial sodium/hydrogen exchanger 9B2
    mitochondrial sodium/hydrogen exchanger NHA2
    sodium/hydrogen exchanger-like domain-containing protein 2
    solute carrier family 9 subfamily B member 2
    solute carrier family 9, subfamily B (NHA2, cation proton antiporter 2), member 2
    solute carrier family 9, subfamily B (cation proton antiporter 2), member 2

    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.

    mRNA and Protein(s)

    1. NM_001300754.2 → NP_001287683.1  sodium/hydrogen exchanger 9B2 isoform 2

      See identical proteins and their annotated locations for NP_001287683.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and lacks an in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.
      Source sequence(s)
      AC097485
      Consensus CDS
      CCDS75174.1
      UniProtKB/TrEMBL
      B7Z488, E9PE63
      Related
      ENSP00000422477.1, ENST00000503230.5
      Conserved Domains (1) summary
      cl01133
      Location:119 → 480
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    2. NM_001300756.2 → NP_001287685.1  sodium/hydrogen exchanger 9B2 isoform 3

      See identical proteins and their annotated locations for NP_001287685.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) lacks two alternate exons in the central and 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC097485
      Consensus CDS
      CCDS75173.1
      UniProtKB/TrEMBL
      B7Z676
      Related
      ENSP00000425385.1, ENST00000503103.5
      Conserved Domains (1) summary
      cl01133
      Location:119 → 356
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    3. NM_001370199.1 → NP_001357128.1  sodium/hydrogen exchanger 9B2 isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC097485
      Conserved Domains (1) summary
      cl01133
      Location:176 → 413
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    4. NM_001370200.1 → NP_001357129.1  sodium/hydrogen exchanger 9B2 isoform 5

      Status: VALIDATED

      Source sequence(s)
      AC097485
      UniProtKB/TrEMBL
      B7Z488
      Conserved Domains (1) summary
      cl01133
      Location:197 → 475
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    5. NM_001370201.1 → NP_001357130.1  sodium/hydrogen exchanger 9B2 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC083826, AC097485
      Consensus CDS
      CCDS3662.1
      UniProtKB/Swiss-Prot
      B5ME52, Q6ZMD8, Q86UD5, Q96D95
      UniProtKB/TrEMBL
      B7Z488
      Conserved Domains (1) summary
      cl01133
      Location:176 → 537
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    6. NM_001370202.1 → NP_001357131.1  sodium/hydrogen exchanger 9B2 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC083826, AC097485
      Consensus CDS
      CCDS3662.1
      UniProtKB/Swiss-Prot
      B5ME52, Q6ZMD8, Q86UD5, Q96D95
      UniProtKB/TrEMBL
      B7Z488
      Related
      ENSP00000354574.3, ENST00000362026.7
      Conserved Domains (1) summary
      cl01133
      Location:176 → 537
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    7. NM_001370203.1 → NP_001357132.1  sodium/hydrogen exchanger 9B2 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC097485
      Consensus CDS
      CCDS75174.1
      UniProtKB/TrEMBL
      B7Z488, E9PE63
      Conserved Domains (1) summary
      cl01133
      Location:119 → 480
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    8. NM_001370204.1 → NP_001357133.1  sodium/hydrogen exchanger 9B2 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC083826, AC097485
      Consensus CDS
      CCDS75174.1
      UniProtKB/TrEMBL
      B7Z488, E9PE63
      Conserved Domains (1) summary
      cl01133
      Location:119 → 480
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    9. NM_001370205.1 → NP_001357134.1  sodium/hydrogen exchanger 9B2 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC083826, AC097485
      Consensus CDS
      CCDS75173.1
      UniProtKB/TrEMBL
      B7Z676
      Conserved Domains (1) summary
      cl01133
      Location:119 → 356
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    10. NM_001370206.1 → NP_001357135.1  sodium/hydrogen exchanger 9B2 isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC083826, AC097485
      Conserved Domains (1) summary
      cl01133
      Location:176 → 413
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    11. NM_001370207.1 → NP_001357136.1  sodium/hydrogen exchanger 9B2 isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC097485
      Conserved Domains (1) summary
      cl01133
      Location:176 → 413
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    12. NM_178833.7 → NP_849155.2  sodium/hydrogen exchanger 9B2 isoform 1

      See identical proteins and their annotated locations for NP_849155.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC097485
      Consensus CDS
      CCDS3662.1
      UniProtKB/Swiss-Prot
      B5ME52, Q6ZMD8, Q86UD5, Q96D95
      UniProtKB/TrEMBL
      B7Z488
      Related
      ENSP00000378265.3, ENST00000394785.9
      Conserved Domains (1) summary
      cl01133
      Location:176 → 537
      Na_H_Exchanger; Sodium/hydrogen exchanger family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      103018029..103077319 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      106329916..106389210 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q86UD5.2 GenPept UniProtKB/Swiss-Prot:Q86UD5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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