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

Gene ID: 11148, updated on 8-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (108296548..108378285)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (110942318..111098074)
105.20220307 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 immune-regulatory roles in cancer. Mortezaee K. Biomed Pharmacother, 2023 Jun. PMID 37011487
  2. Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer. Kula A, et al. Int J Mol Sci, 2023 Mar 20. PMID 36982953, Free PMC Article
  3. Immunosuppression by Inflammation-Stimulated Amplification of Myeloid-Derived Suppressor Cells and Changes in Expression of Immune Checkpoint HHLA2 in Chronic Obstructive Pulmonary Disease. Xu L, et al. Int J Chron Obstruct Pulmon Dis, 2023. PMID 36846109, Free PMC Article
  4. Increased co-expression of stromal HHLA2 and fibroblast activation protein in upper tract urothelial carcinoma. Nishihara D, et al. Int Urol Nephrol, 2023 Apr. PMID 36598731, Free PMC Article
  5. Silencing tumor-intrinsic HHLA2 potentiates the anti-tumoral effect of paclitaxel on MG63 cells: Another side of immune checkpoint. Ahangar NK, et al. Gene, 2023 Mar 1. PMID 36535461

See all (53) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Regulation of HHLA2 expression in kidney cancer and myeloid cells.
    Title: Regulation of HHLA2 expression in kidney cancer and myeloid cells.
  3. HHLA2 immune-regulatory roles in cancer.
    Title: HHLA2 immune-regulatory roles in cancer.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Silencing tumor-intrinsic HHLA2 potentiates the anti-tumoral effect of paclitaxel on MG63 cells: Another side of immune checkpoint.
    Title: Silencing tumor-intrinsic HHLA2 potentiates the anti-tumoral effect of paclitaxel on MG63 cells: Another side of immune checkpoint.
  10. HHLA2 predicts improved prognosis of anti-PD-1/PD-L1 immunotherapy in patients with melanoma.
    Title: HHLA2 predicts improved prognosis of anti-PD-1/PD-L1 immunotherapy in patients with melanoma.
Submit: New GeneRIF Correction See all GeneRIFs (43)

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)

Genotypes

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 molecular_function ND
No biological Data available
more info
  
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 cellular_component ND
No biological Data available
more info
  
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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NEW Try the new Transcript table

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_2023_10

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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