HHLA2 (HERV-H LTR-Associating 2)
Immune checkpoint molecule of the B7 family with roles in cancer immunotherapy and T-cell regulation.
Gene Information Card
| Symbol | HHLA2 |
|---|---|
| Full Name | HERV-H LTR-Associating 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q13.13 |
| NCBI Gene ID | 11148 ncbi.nlm.nih.gov/gene/11148 |
| Ensembl ID | ENSG00000114455 |
| UniProt ID | Q9UM44 |
| OMIM ID | 606202 |
| HGNC ID | 4904 |
| Aliases | B7-H7, B7y, B7-H5, B7H7 |
Description
HHLA2 (HERV-H LTR-Associating 2) is a member of the B7 family of immune checkpoint proteins. It is a transmembrane glycoprotein that binds to the receptor TMIGD2 (CD28H) and inhibits T-cell proliferation and cytokine production. HHLA2 is broadly expressed in human tissues and is frequently overexpressed in various cancers, making it a target for cancer immunotherapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of HHLA2 on tumor cells suppresses anti-tumor T-cell responses via TMIGD2 binding. | PMID: 25799045, 29301962 |
| Autoimmune diseases | Dysregulation of HHLA2 may contribute to altered T-cell activation in autoimmune conditions. | PMID: 31511494 |
| Infectious diseases | HHLA2 expression on antigen-presenting cells may modulate T-cell responses during chronic infection. | PMID: 30361261 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Placenta | 15.2 | High |
| Small intestine | 6.4 | Low |
| Spleen | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 18.5 | High expression |
| MCF7 (breast cancer) | 9.2 | Medium expression |
| HepG2 (liver cancer) | 5.6 | Low expression |
| Jurkat (T-cell) | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | <0.1% | Unknown functional effect |
| c.1024G>A (p.Val342Met) | Missense | <0.1% | Unknown functional effect |
| c.1235_1236insA | Frameshift | <0.1% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.1235_1236insA) are predicted to truncate the protein and abolish TMIGD2 binding.
Gain of Function (GOF)
No gain-of-function mutations have been reported in HHLA2.
Dominant Negative (DN)
No dominant-negative mutations have been described for HHLA2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Immune checkpoint signaling (B7 family pathway)
• T-cell receptor signaling pathway (modulation)
Protein Summary
HHLA2 is a 414-amino-acid type I transmembrane protein with an extracellular IgV-like domain and a short cytoplasmic tail. It is expressed on antigen-presenting cells, epithelial cells, and many tumors. Binding to TMIGD2 on T cells delivers a co-inhibitory signal, reducing T-cell proliferation and cytokine secretion. HHLA2 is considered an immune checkpoint target for cancer therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HHLA2 Knockout HEK293 Cell Line | EDJ-KQ3221 | Human | 11148 | Details Get a Quote |
| HHLA2 Knockout HeLa Cell Line | EDJ-KQ55584 | Human | 11148 | Details Get a Quote |
| HHLA2 Knockout A-549 Cell Line | EDJ-KQ64081 | Human | 11148 | Details Get a Quote |
| HHLA2 Knockout HCT 116 Cell Line | EDJ-KQ72531 | Human | 11148 | Details Get a Quote |
