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    HHLA2 HHLA2 member of B7 family [ Homo sapiens (human) ]

    Gene ID: 11148, updated on 27-Nov-2024

    Summary

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    Official Symbol
    HHLA2provided by HGNC
    Official Full Name
    HHLA2 member of B7 familyprovided by HGNC
    Primary source
    HGNC:HGNC:4905
    See related
    Ensembl:ENSG00000114455 MIM:604371; AllianceGenome:HGNC:4905
    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
    B7y; B7H7; B7-H5; B7-H7
    Summary
    This gene encodes a protein ligand found on the surface of monocytes. The encoded protein is thought to regulate cell-mediated immunity by binding to a receptor on T lymphocytes and inhibiting the proliferation of these cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
    Expression
    Biased expression in small intestine (RPKM 36.3), colon (RPKM 25.6) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HHLA2 in Genome Data Viewer
    Location:
    3q13.13
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (108296548..108378285)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (110942318..111098074)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (108015395..108097132)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak4760 silencer Neighboring gene MPRA-validated peak4761 silencer Neighboring gene intraflagellar transport 57 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20216 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:107941185-107941478 Neighboring gene uncharacterized LOC124909405 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14596 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 17 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:108095636-108096835 Neighboring gene uncharacterized LOC124900545 Neighboring gene Sharpr-MPRA regulatory region 5857 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20218 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20219 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20220 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20221 Neighboring gene myosin heavy chain 15 Neighboring gene uncharacterized LOC124909406

    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. HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1. Jing CY, et al. J Immunother Cancer, 2019 Mar 18. PMID 30885276, Free PMC Article
    2. HHLA2 Immune Checkpoint Is a Novel Prognostic Predictor in Hepatocellular Carcinoma. Liao X, et al. Am J Clin Pathol, 2022 Jul 1. PMID 35084443
    3. HHLA2 deficiency inhibits non-small cell lung cancer progression and THP-1 macrophage M2 polarization. Sun W, et al. Cancer Med, 2021 Aug. PMID 34152094, Free PMC Article
    4. B7-H7 Is Inducible on T Cells to Regulate Their Immune Response and Serves as a Marker for Exhaustion. Luu K, et al. Front Immunol, 2021. PMID 34140952, Free PMC Article
    5. H Long Terminal Repeat-Associating 2 (HHLA2) is a Biomarker of Advanced Stage Hepatocellular Carcinoma and Promotes Tumor Cell Development In Vitro. Luo M, et al. Med Sci Monit, 2021 May 15. PMID 33990536, Free PMC Article

    See all (56) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HHLA2 promotes hepatoma cell proliferation, migration, and invasion via SPP1/PI3K/AKT signaling pathway.
      Title: HHLA2 promotes hepatoma cell proliferation, migration, and invasion via SPP1/PI3K/AKT signaling pathway.
    2. HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.
      Title: HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.
    3. HHLA2 is more significantly associated with poor prognosis in TSCC than PD-L1.
      Title: HHLA2 is more significantly associated with poor prognosis in TSCC than PD-L1.
    4. Regulation of HHLA2 expression in kidney cancer and myeloid cells.
      Title: Regulation of HHLA2 expression in kidney cancer and myeloid cells.
    5. HHLA2 immune-regulatory roles in cancer.
      Title: HHLA2 immune-regulatory roles in cancer.
    6. KIR3DL3-HHLA2 and TMIGD2-HHLA2 pathways: The dual role of HHLA2 in immune responses and its potential therapeutic approach for cancer immunotherapy.
      Title: KIR3DL3-HHLA2 and TMIGD2-HHLA2 pathways: The dual role of HHLA2 in immune responses and its potential therapeutic approach for cancer immunotherapy.
    7. Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer.
      Title: Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer.
    8. Increased co-expression of stromal HHLA2 and fibroblast activation protein in upper tract urothelial carcinoma.
      Title: Increased co-expression of stromal HHLA2 and fibroblast activation protein in upper tract urothelial carcinoma.
    9. Decrease of Membrane B7-H5 on CD14+ Cells in Severe Acute Pancreatitis Is Related to RANSON Scores and APACHE II Scores.
      Title: Decrease of Membrane B7-H5 on CD14+ Cells in Severe Acute Pancreatitis Is Related to RANSON Scores and APACHE II Scores.
    10. Immunosuppression by Inflammation-Stimulated Amplification of Myeloid-Derived Suppressor Cells and Changes in Expression of Immune Checkpoint HHLA2 in Chronic Obstructive Pulmonary Disease.
      Title: Immunosuppression by Inflammation-Stimulated Amplification of Myeloid-Derived Suppressor Cells and Changes in Expression of Immune Checkpoint HHLA2 in Chronic Obstructive Pulmonary Disease.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell costimulation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in T cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of activated T cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cytokine production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cytokine production IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    HERV-H LTR-associating protein 2
    Names
    HERV-H LTR-associating 2
    human endogenous retrovirus-H long terminal repeat-associating protein 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_001282556.2 → NP_001269485.1  HERV-H LTR-associating protein 2 isoform a precursor

      See identical proteins and their annotated locations for NP_001269485.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the use of an alternate promoter and differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform a).
      Source sequence(s)
      AC078855, AC135308, AK000692, BM980981, BP293912
      Consensus CDS
      CCDS46883.1
      UniProtKB/Swiss-Prot
      B4DKN2, D3DN60, Q9NWQ6, Q9UM44
      Related
      ENSP00000419207.1, ENST00000467761.6
      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    2. NM_001282557.2 → NP_001269486.1  HERV-H LTR-associating protein 2 isoform a precursor

      See identical proteins and their annotated locations for NP_001269486.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the use of an alternate promoter and differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform a).
      Source sequence(s)
      AC135308, AF126162, BM980981
      Consensus CDS
      CCDS46883.1
      UniProtKB/Swiss-Prot
      B4DKN2, D3DN60, Q9NWQ6, Q9UM44
      Related
      ENSP00000417856.2, ENST00000489514.6
      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    3. NM_001282558.2 → NP_001269487.1  HERV-H LTR-associating protein 2 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the use of an alternate promoter, differs in the 5' UTR and lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. The encoded protein (isoform b) is shorter than isoform a.
      Source sequence(s)
      AC078855, AC135308, AK315109, BC035971, BM980981
      Consensus CDS
      CCDS74975.1
      UniProtKB/TrEMBL
      C9J7D0
      Related
      ENSP00000418284.1, ENST00000491820.5
      Conserved Domains (4) summary
      cd00098
      Location:140 → 225
      IgC; Immunoglobulin Constant domain
      smart00410
      Location:237 → 334
      IG_like; Immunoglobulin like
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:61 → 122
      Ig; Immunoglobulin domain

    4. NM_001282559.2 → NP_001269488.1  HERV-H LTR-associating protein 2 isoform c

      See identical proteins and their annotated locations for NP_001269488.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) represents the use of an alternate promoter, and has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at an alternate start codon, compared to variant 1. The encoded protein (isoform c) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AC078855, AC135308, AK296644, BC035971, BM980981
      Consensus CDS
      CCDS63713.1
      UniProtKB/TrEMBL
      H7C523
      Related
      ENSP00000418345.1, ENST00000467562.5
      Conserved Domains (3) summary
      cd00098
      Location:76 → 161
      IgC; Immunoglobulin Constant domain
      smart00410
      Location:173 → 270
      IG_like; Immunoglobulin like
      pfam07686
      Location:167 → 266
      V-set; Immunoglobulin V-set domain

    5. NM_001370244.1 → NP_001357173.1  HERV-H LTR-associating protein 2 isoform a precursor

      Status: REVIEWED

      Source sequence(s)
      AC078855, AC135308
      Consensus CDS
      CCDS46883.1
      UniProtKB/Swiss-Prot
      B4DKN2, D3DN60, Q9NWQ6, Q9UM44
      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    6. NM_007072.4 → NP_009003.1  HERV-H LTR-associating protein 2 isoform a precursor

      See identical proteins and their annotated locations for NP_009003.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AC078855, AC135308, BC035971, BM980981
      Consensus CDS
      CCDS46883.1
      UniProtKB/Swiss-Prot
      B4DKN2, D3DN60, Q9NWQ6, Q9UM44
      Related
      ENSP00000350402.5, ENST00000357759.9
      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      108296548..108378285
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047447369.1 → XP_047303325.1  HERV-H LTR-associating protein 2 isoform X1

    2. XM_011512362.3 → XP_011510664.1  HERV-H LTR-associating protein 2 isoform X1

      See identical proteins and their annotated locations for XP_011510664.1

      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    3. XM_005247080.4 → XP_005247137.1  HERV-H LTR-associating protein 2 isoform X2

      See identical proteins and their annotated locations for XP_005247137.1

      UniProtKB/Swiss-Prot
      B4DKN2, D3DN60, Q9NWQ6, Q9UM44
      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    4. XM_011512367.4 → XP_011510669.1  HERV-H LTR-associating protein 2 isoform X3

      Conserved Domains (4) summary
      cd00098
      Location:140 → 225
      IgC; Immunoglobulin Constant domain
      smart00410
      Location:237 → 334
      IG_like; Immunoglobulin like
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:61 → 122
      Ig; Immunoglobulin domain

    5. XM_011512364.3 → XP_011510666.1  HERV-H LTR-associating protein 2 isoform X1

      See identical proteins and their annotated locations for XP_011510666.1

      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    6. XM_011512363.3 → XP_011510665.1  HERV-H LTR-associating protein 2 isoform X1

      See identical proteins and their annotated locations for XP_011510665.1

      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    7. XM_047447368.1 → XP_047303324.1  HERV-H LTR-associating protein 2 isoform X1

    8. XM_024453326.2 → XP_024309094.1  HERV-H LTR-associating protein 2 isoform X1

      Conserved Domains (2) summary
      pfam07686
      Location:231 → 330
      V-set; Immunoglobulin V-set domain
      cl11960
      Location:47 → 125
      Ig; Immunoglobulin domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      110942318..111098074
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054345085.1 → XP_054201060.1  HERV-H LTR-associating protein 2 isoform X2

    2. XM_054345084.1 → XP_054201059.1  HERV-H LTR-associating protein 2 isoform X2

    3. XM_054345081.1 → XP_054201056.1  HERV-H LTR-associating protein 2 isoform X1

    4. XM_054345086.1 → XP_054201061.1  HERV-H LTR-associating protein 2 isoform X3

    5. XM_054345082.1 → XP_054201057.1  HERV-H LTR-associating protein 2 isoform X1

    6. XM_054345080.1 → XP_054201055.1  HERV-H LTR-associating protein 2 isoform X1

    7. XM_054345079.1 → XP_054201054.1  HERV-H LTR-associating protein 2 isoform X1

    8. XM_054345083.1 → XP_054201058.1  HERV-H LTR-associating protein 2 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UM44.1 GenPept UniProtKB/Swiss-Prot:Q9UM44

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