TRG

Summary

TRG (T cell receptor gamma locus, HGNC:12271) is a protein-coding gene on chromosome 7p14.

T cell receptors recognize foreign antigens which have been processed as small peptides and bound to major histocompatibility complex (MHC) molecules at the surface of antigen presenting cells (APC). Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. If both delta and gamma rearrangements produce functional chains, the cell expresses delta and gamma. If not, the cell proceeds to rearrange the beta and alpha loci. This region represents the germline organization of the T cell receptor gamma locus. The gamma locus includes V (variable), J (joining), and C (constant) segments. During T cell development, the gamma chain is synthesized by a recombination event at the DNA level joining a V segment with a J segment; the C segment is later joined by splicing at the RNA level. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random addition of nucleotides by terminal deoxynucleotidyltransferase. Several V segments of the gamma locus are known to be incapable of encoding a protein and are considered pseudogenes. Somatic rearrangement of the gamma locus has been observed in T cells derived from patients with T cell leukemia and ataxia telangiectasia.

Source: NCBI Gene 6965 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12271
Approved symbol	TRG
Name	T cell receptor gamma locus
Location	7p14
Locus type	gene with protein product
Status	Approved
Entrez	6965

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

None — 0 exons

Expression profiles

Top tissues by expression

0 total, by Bgee expression score (0-100, higher = more expressed):

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• clinical association between TCR-gamma and early-onset colorectal cancer (PMID:11833498)
• Expression of this receptor is expanded in T cells in nasal T-cell lymphoma and chronic active Epstein-Barr virus infection. (PMID:12707047)
• T-gamma receptor restriction in peripheral lymphocytes of patients with Behcet’s disease (PMID:12918704)
• Pattern of TCR-gamma gene rearrangement in gastrointestinal lymphomas are similar to that of nodular lymphomas. Gene rearrangement pattern involves monoallelic and biallelic (or oligoclonal) gene rearrangement. (PMID:15052681)
• Appearance of clonal bands on Southern blot analysis of TCR beta and gamma genes implies that the TIL in thymomas experience partial gene rearrangement just before the connection between the DJC complex and a locus of the V region. (PMID:15905344)
• A higher number of activated and IFN-gamma producing gamma delta T-cells are observed in patients with active Takayasu’s arteritis (PMID:16307908)
• Data are compatible with an instructive role for the TCR in alphabeta vs gammadelta lineage commitment, with gammadelta development as the default pathway for human thymocyte development. (PMID:16424183)
• Fetal gammadelta T cell depletion might be a mechanism for impaired neonatal immunity and lowered responses to pediatric vaccines. (PMID:18440637)
• Changes in Vgamma2Vdelta2 T cells, along with concomitant effects on natural killer cells may elevate risk of malignancy during AIDS> (PMID:18495780)
• Dysregulation of the host mevalonate pathway during early bacterial infection activates human TCR gamma delta cells. (PMID:18624305)
• data suggest that reduction in the proportion of gammadelta T cells and granzyme B gene polymorphism leads to defective immune function in breast cancer patients (PMID:19446661)
• human eosinophils express a functional gammadeltaTCR/CD3 with similar, but not identical, characteristics to gammadeltaTCR from gammadeltaT cells (PMID:19536290)
• T-cell receptor gamma gene rearrangement findings of mycosis fungoides in patients younger than age 20 years (PMID:19583687)
• TCRgamma genes make up for their lack of separate D segments with distinct D-like segments built into the 5’ ends of their J segments. Most of the 5’ ends of TCRJgamma segments show base & AA sequence similarities with TCRDbeta segments. (PMID:19756574)
• Freshly isolated human peripheral blood gamma delta T cells can phagocytose Escherichia coli and synthetic microbeads via antibody opsonization and CD16 (FcgammaRIII), leading to antigen processing and presentation on histocompatibility class II antigen. (PMID:19843947)
• These findings support the association between reduced copy-number at TCRgamma and childhood allergic asthma (PMID:20553737)
• Vgamma9Vdelta2 T cells expanded by Mycobacterium-infected dendritic cells show a central memory phenotype but lack immediate effector functions. (PMID:20592281)
• T-Cell Receptor gamma-Chain rearrangement is associated with an aggressive systemic juvenile xanthogranuloma clonally related to a preceding T-cell acute lymphoblastic leukemia. (PMID:20848640)
• NKG2A expression on gammadelta lymphoproliferative Disease of Large Granular Lymphocytes correlates with asymptomatic pathology, even in the presence of NKG2C coexpression. (PMID:20952657)
• Report nonhepatosplenic gamma-delta T-cell lymphomas representing a spectrum of aggressive cytotoxic T-cell lymphomas with a mainly extranodal presentation. (PMID:21753698)
• Our results suggest a lack of structural rearrangements of TCRAD, TCRB, and TCRG genes detected by FISH in CTCL patients. (PMID:21872828)
• Studies suggest that activated human gammadelta T cells can efficiently present PRAME and STEAP1-derived epitopes and allow breaking tolerance against these tumor-associated self-antigens. (PMID:21928126)
• psoriasis patients, gammadelta T cells were greatly increased in affected skin and produced large amounts of IL-17 (PMID:21982596)
• Findings suggest that Vgamma9Vdelta2 T cell-mediated production of granulysin as an underestimated immune effector in malaria. (PMID:22045985)
• [Review] Studies in a murine model provide important information for investigations of gammadelta T cells, mainly Vgamma1-positive cells, that are involved in immediate control of West Nile virus and the host TCRG immune response in humans. (PMID:22078709)
• G-CSF mobilization not only influences the distribution and expression levels of T cell receptors (TCR) of gamma delta+ T cells (TRGV and TRDV) repertoire, but also changes the clonality of gamma delta+ T cells. (PMID:22171570)
• Data indicate that that CD16 could stimulate gammadelta T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. (PMID:22180442)
• TCRG and TCRA analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon aging. (PMID:23000520)
• A second combinatorial immune receptor found in monocytes/macrophages is based on the TCRgamma-delta. (PMID:23312956)
• The surface TCR expression of primary alphabeta and gammadelta T cells from healthy donors carrying a single null or leaky mutation in CD3G (gamma+/-) or CD3D (delta+/-, delta+/leaky) with that of normal controls, were compared. (PMID:23336327)
• Data indicate that gammadelta T cell functions are specifically impaired in situ by active tuberculosis. (PMID:23770719)
• Data suggest that both CD8+ alphabeta and gammadelta T cells are activated in an antigen-specific manner in response to dietary gluten. (PMID:23878218)
• reduced TRECs level in the colonic mucosa, together with our previously demonstrated enhanced expression of Ki67(+) T cells, suggests local expansion of resident T lymphocytes in the inflamed mucosa of MC patients. (PMID:23956982)
• The gamma-delta TCR docked orthogonally, over the A’ pocket of CD1d, in which the Vdelta1-chain, and the germ line-encoded CDR1d loop, dominated interactions with CD1d. (PMID:24076636)
• T cell receptor delta gamma + intraepithelial lymphocytes (IEL) are developmentally the prominent IEL subtype in the immature murine and human gut. (PMID:24905458)
• Gamma-delta T cells and their corresponding T cell receptors hold pomise for cancer immunotherapy. (Review) (PMID:25864915)
• Data indicate that gamma delta (GD) T cells are essential components of the adaptive and innate immune system in the female reproductive tract. (PMID:27078021)
• Vgamma9Vdelta2 TCR activation is modulated by the GTPase activity of RhoB and its redistribution to BTN3A1. (PMID:27210746)
• The nanobodies (VHHs) are useful for flow cytometry, magnetic-activated cell sorting and immunocytochemistry to study Vgamma9Vdelta2-T cells. (PMID:27373969)
• Data indicate the expression of a chimeric T-cell receptor alpha beta (alphabeta TCR) harboring the immunoglobulin-like (Ig) domain of T-cell receptor gamma delta (gammadelta TCR) in Jurkat T cells. (PMID:27412930)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Canonical reviewed UniProt: None (reviewed: )

All UniProt accessions (0):

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.