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    SH2D1A SH2 domain containing 1A [ Homo sapiens (human) ]

    Gene ID: 4068, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SH2D1Aprovided by HGNC
    Official Full Name
    SH2 domain containing 1Aprovided by HGNC
    Primary source
    HGNC:HGNC:10820
    See related
    Ensembl:ENSG00000183918 MIM:300490; AllianceGenome:HGNC:10820
    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
    LYP; SAP; XLP; DSHP; EBVS; IMD5; XLPD; MTCP1; XLPD1; SAP/SH2D1A
    Summary
    This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in lymph node (RPKM 17.0), spleen (RPKM 6.1) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SH2D1A in Genome Data Viewer
    Location:
    Xq25
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (124346563..124373160)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (122657134..122683529)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (123480413..123507010)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene nucleophosmin 1 pseudogene 34 Neighboring gene uncharacterized LOC105373331 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:123539864-123541063 Neighboring gene TEX13 family member D Neighboring gene teneurin transmembrane protein 1 Neighboring gene NANOG hESC enhancer GRCh37_chrX:123622217-123622915 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:123667881-123668476 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:123668477-123669070 Neighboring gene ribosomal protein S26 pseudogene 57

    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 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. SLAM-associated protein deficiency causes imbalanced early signal transduction and blocks downstream activation in T cells from X-linked lymphoproliferative disease patients. Sanzone S, et al. J Biol Chem, 2003 Aug 8. PMID 12766168
    2. Up-Regulation of LAT1 during Antiandrogen Therapy Contributes to Progression in Prostate Cancer Cells. Xu M, et al. J Urol, 2016 May. PMID 26682754
    3. Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched Unrelated Cord Blood Transplant. Gray PE, et al. J Clin Immunol, 2015 Oct. PMID 26433589
    4. Study of SH2D1A gene mutation in paediatric patients with B-cell lymphoma. Koochakzadeh L, et al. Allergol Immunopathol (Madr), 2015 Nov-Dec. PMID 25982576
    5. Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes. Veillette A, et al. Immunity, 2007 Nov. PMID 18031694

    See all (152) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.
      Title: SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.
    2. Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
      Title: Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
    3. Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naive Boy Is Associated With a Novel SH2D1A Mutation.
      Title: Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-NaĂŻve Boy Is Associated With a Novel SH2D1A Mutation.
    4. Epstein-Barr Virus-Negative Granulomatous Disease Due to SAP Deficiency.
      Title: Epstein-Barr Virus-Negative Granulomatous Disease Due to SAP Deficiency.
    5. SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.
      Title: SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.
    6. SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
      Title: SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
    7. Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
      Title: Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
    8. A Novel Missense Mutation Affecting the N-terminal Domain of SAP Protein in X-linked Lymphoproliferative Disease.
      Title: A Novel Missense Mutation Affecting the N-terminal Domain of SAP Protein in X-linked Lymphoproliferative Disease.
    9. hese data indicate NK cell-mediated cytotoxicity is not equally affected in Acute lymphoblastic leukemia (ALL) patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count >/=50,000xmm3
      Title: Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.
    10. A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.
      Title: A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.
    Submit: New GeneRIF Correction See all GeneRIFs (89)

    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

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2021-01-27)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2021-01-27)

    ClinGen Genome Curation PagePubMed

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    • FLJ18687, FLJ92177

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-macromolecule adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell-cell signaling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular defense response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in humoral immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in natural killer cell activation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in natural killer cell mediated cytotoxicity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of natural killer cell mediated cytotoxicity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of immune response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    SH2 domain-containing protein 1A
    Names
    Duncan disease SH2-protein
    SLAM associated protein/SH2 domain protein 1A
    SLAM-associated protein
    T cell signal transduction molecule SAP
    signaling lymphocyte activation molecule-associated protein
    signaling lymphocytic activation molecule-associated protein

    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

    1. NG_007464.1 RefSeqGene

      Range
      4983..31861
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_106

    mRNA and Protein(s)

    1. NM_001114937.3 → NP_001108409.1  SH2 domain-containing protein 1A isoform 2

      See identical proteins and their annotated locations for NP_001108409.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AA190204, AF100541, AL023657, DA007747
      Consensus CDS
      CCDS48162.1
      UniProtKB/Swiss-Prot
      O60880
      Related
      ENSP00000353126.4, ENST00000360027.5
      Conserved Domains (1) summary
      cd10400
      Location:2 → 104
      SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a

    2. NM_002351.5 → NP_002342.1  SH2 domain-containing protein 1A isoform 1

      See identical proteins and their annotated locations for NP_002342.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AA190204, AL023657
      Consensus CDS
      CCDS14608.1
      UniProtKB/Swiss-Prot
      A8MSW0, O60880, O95383, O95384, O95385, O95386, Q6FGS6, Q9UNR0
      Related
      ENSP00000360181.5, ENST00000371139.9
      Conserved Domains (1) summary
      cd10400
      Location:2 → 104
      SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      124346563..124373160
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      122657134..122683529
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60880.1 GenPept UniProtKB/Swiss-Prot:O60880

    Gene LinkOut

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

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