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Aliases for HHLA2 Gene

Aliases for HHLA2 Gene

  • HERV-H LTR-Associating 2 2 3 5
  • Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 3 4
  • B7-H5 3
  • B7-H7 3
  • B7H7 3
  • B7y 3

External Ids for HHLA2 Gene

Previous GeneCards Identifiers for HHLA2 Gene

  • GC03P104824
  • GC03U900035
  • GC03P109351
  • GC03P109342
  • GC03P109498
  • GC03P108015
  • GC03P105394

Summaries for HHLA2 Gene

Entrez Gene Summary for HHLA2 Gene

  • 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]

GeneCards Summary for HHLA2 Gene

HHLA2 (HERV-H LTR-Associating 2) is a Protein Coding gene. Among its related pathways are T Cell Co-Signaling Pathway: Ligand-Receptor Interactions. An important paralog of this gene is VTCN1.

UniProtKB/Swiss-Prot for HHLA2 Gene

  • Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HHLA2 Gene

Genomics for HHLA2 Gene

Regulatory Elements for HHLA2 Gene

Enhancers for HHLA2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HHLA2 on UCSC Golden Path with GeneCards custom track

Genomic Location for HHLA2 Gene

108,296,485 bp from pter
108,388,971 bp from pter
92,487 bases
Plus strand

Genomic View for HHLA2 Gene

Genes around HHLA2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HHLA2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HHLA2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HHLA2 Gene

Proteins for HHLA2 Gene

  • Protein details for HHLA2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    HERV-H LTR-associating protein 2
    Protein Accession:
    Secondary Accessions:
    • B4DKN2
    • D3DN60
    • Q9NWQ6

    Protein attributes for HHLA2 Gene

    414 amino acids
    Molecular mass:
    46850 Da
    Quaternary structure:
    • Interacts with TMIGD2.
    • Sequence=BAA91323.1; Type=Erroneous termination; Positions=221; Note=Translated as Trp.; Evidence={ECO:0000305};

    Alternative splice isoforms for HHLA2 Gene


neXtProt entry for HHLA2 Gene

Proteomics data for HHLA2 Gene at MOPED

Post-translational modifications for HHLA2 Gene

  • Glycosylation at Asn 90, Asn 103, and Asn 318

Antibody Products

  • Abcam antibodies for HHLA2

No data available for DME Specific Peptides for HHLA2 Gene

Domains & Families for HHLA2 Gene

Protein Domains for HHLA2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 Ig-like C1-type (immunoglobulin-like) domain.
  • Contains 1 Ig-like C1-type (immunoglobulin-like) domain.
  • Contains 2 Ig-like V-type (immunoglobulin-like) domains.
genes like me logo Genes that share domains with HHLA2: view

Function for HHLA2 Gene

Molecular function for HHLA2 Gene

UniProtKB/Swiss-Prot Function:
Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.
UniProtKB/Swiss-Prot Induction:
Up-regulated in antigen-presenting cells in response to inflammation. Induced in dendritic cells in response to IFNG, poly(I:C) or heat-killed Listeria monocytogenes (at protein level).
genes like me logo Genes that share phenotypes with HHLA2: view

Animal Model Products

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for HHLA2 Gene

Localization for HHLA2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HHLA2 Gene

Membrane; Single-pass type I membrane protein.

Subcellular locations from

Jensen Localization Image for HHLA2 Gene COMPARTMENTS Subcellular localization image for HHLA2 gene
Compartment Confidence
extracellular 3
plasma membrane 3
lysosome 1
peroxisome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for HHLA2 Gene

Pathways & Interactions for HHLA2 Gene

genes like me logo Genes that share pathways with HHLA2: view

Pathways by source for HHLA2 Gene

1 R&D Systems pathway for HHLA2 Gene

Interacting Proteins for HHLA2 Gene

Gene Ontology (GO) - Biological Process for HHLA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0042104 positive regulation of activated T cell proliferation IDA 23784006
genes like me logo Genes that share ontologies with HHLA2: view

No data available for SIGNOR curated interactions for HHLA2 Gene

Drugs & Compounds for HHLA2 Gene

No Compound Related Data Available

Transcripts for HHLA2 Gene

Unigene Clusters for HHLA2 Gene

HERV-H LTR-associating 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HHLA2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12
SP2: -
SP3: - -
SP4: -

Relevant External Links for HHLA2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HHLA2 Gene

mRNA expression in normal human tissues for HHLA2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HHLA2 Gene

This gene is overexpressed in Colon - Transverse (x30.6) and Small Intestine - Terminal Ileum (x13.8).

Protein differential expression in normal tissues from HIPED for HHLA2 Gene

This gene is overexpressed in Rectum (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HHLA2 Gene

SOURCE GeneReport for Unigene cluster for HHLA2 Gene Hs.252351

mRNA Expression by UniProt/SwissProt for HHLA2 Gene

Tissue specificity: Expressed at high levels in colon, kidney, testis, lung and pancreas, and at lower levels in small intestine, liver and skeletal muscle. In immune cells, highly expressed in B-cells, dendritic cells and macrophages. Not detected in T-cells.
genes like me logo Genes that share expression patterns with HHLA2: view

Protein tissue co-expression partners for HHLA2 Gene

- Elite partner

Primer Products

Orthologs for HHLA2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for HHLA2 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia HHLA2 36
  • 64 (a)
(Monodelphis domestica)
Mammalia HHLA2 36
  • 35 (a)
(Ornithorhynchus anatinus)
Mammalia HHLA2 36
  • 35 (a)
(Pan troglodytes)
Mammalia HHLA2 36
  • 92 (a)
(Gallus gallus)
Aves HHLA2 36
  • 37 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hhla2 35
  • 47.45 (n)
  • 36.3 (a)
(Danio rerio)
Actinopterygii HHLA2 (1 of 4) 36
  • 18 (a)
HHLA2 (2 of 4) 36
  • 17 (a)
HHLA2 (3 of 4) 36
  • 19 (a)
HHLA2 (4 of 4) 36
  • 17 (a)
Species with no ortholog for HHLA2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • mouse (Mus musculus)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HHLA2 Gene

Gene Tree for HHLA2 (if available)
Gene Tree for HHLA2 (if available)

Paralogs for HHLA2 Gene

Paralogs for HHLA2 Gene

(1) SIMAP similar genes for HHLA2 Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with HHLA2: view

Variants for HHLA2 Gene

Sequence variations from dbSNP and Humsavar for HHLA2 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs6779254 - 108,353,451(+) CTTCA(C/T)TTATG intron-variant, nc-transcript-variant, reference, missense
rs3792332 - 108,362,370(-) CCTTT(G/T)TTATG intron-variant, nc-transcript-variant, reference, missense
rs6779094 - 108,362,430(+) TGGAG(A/C)GTAAA intron-variant, nc-transcript-variant, reference, missense
rs752179 -- 108,305,223(+) TTTAT(A/T)TGGGA intron-variant
rs768342 -- 108,296,400(-) CAGAT(A/C)TGAAA upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for HHLA2 Gene

Variant ID Type Subtype PubMed ID
nsv829656 CNV Loss 17160897
nsv829657 CNV Gain 17160897
esv273465 CNV Insertion 20981092
nsv526190 CNV Gain 19592680

Variation tolerance for HHLA2 Gene

Residual Variation Intolerance Score: 92.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.31; 70.58% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for HHLA2 Gene

Disorders for HHLA2 Gene

Relevant External Links for HHLA2

Genetic Association Database (GAD)
Atlas of Genetics and Cytogenetics in Oncology and Haematology:

No disorders were found for HHLA2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for HHLA2 Gene

Publications for HHLA2 Gene

  1. Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3). (PMID: 10444326) Mager D.L. … Freeman J.D. (Genomics 1999) 2 3 4 23 67
  2. B7-H5 costimulates human T cells via CD28H. (PMID: 23784006) Zhu Y. … Chen L. (Nat Commun 2013) 2 3
  3. Evolution of the B7 family: co-evolution of B7H6 and NKp30, identification of a new B7 family member, B7H7, and of B7's historical relationship with the MHC. (PMID: 22488247) Flajnik M.F. … Ohta Y. (Immunogenetics 2012) 2 3
  4. Expression, Clinical Significance, and Receptor Identification of the Newest B7 Family Member HHLA2 Protein. (PMID: 25549724) Janakiram M. … Zang X. (Clin. Cancer Res. 2015) 3
  5. HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function. (PMID: 23716685) Zhao R. … Zang X. (Proc. Natl. Acad. Sci. U.S.A. 2013) 3

Products for HHLA2 Gene

Sources for HHLA2 Gene