TGM2
protein-codingtransglutaminase 2, the group of Transglutaminases
Gene summary
Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. The protein encoded by this gene acts as a monomer, is induced by retinoic acid, and appears to be involved in apoptosis. Finally, the encoded protein is the autoantigen implicated in celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005148
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TGM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004613.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 12 | 26 | |||
| missense | 99 | 2 | 3 | 104 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 104 | 16 | 15 | 135 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004604.2 | 13 | MANE Select | |
| Ensembl | ENSP00000355330.2 | 13 | MANE Select | |
| RefSeq | NP_001310245.1 | 13 | Standard | |
| RefSeq | NP_001310246.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Huntington,s disease - Homo sapiens (human)
- phospholipase c delta in phospholipid associated cell signaling
- Thromboxane A2 receptor signaling
- Alpha9 beta1 integrin signaling events
- Beta1 integrin cell surface interactions
Biological Process
- blood vessel remodeling
- isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine
- negative regulation of endoplasmic reticulum calcium ion concentration
- positive regulation of apoptotic process
- positive regulation of I-kappaB kinase/NF-kappaB signaling
Molecular Function
- protein-glutamine gamma-glutamyltransferase activity
- protein binding
- GTP binding
- protein domain specific binding
- metal ion binding
Cellular Component
- mitochondrion
- endoplasmic reticulum
- cytosol
- focal adhesion
- intrinsic component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361475
- Coding exons
- 13
- Length
- 38118
- Individuals with no LoFs
- 125626
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 122
- Defined
- 125748
- p
- 0.000485
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.536 | 400 | 431 | 0.927 | 0.0000299 | 4487 |
| Missense (PolyPhen) | 127 | 156.77 | 0.81011 | 1594 | ||
| Synonymous | -0.467 | 196 | 188 | 1.04 | 0.0000141 | 1336 |
| Loss of Function | 0.703 | 29 | 33.4 | 0.869 | 0.00000172 | 356 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00045 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00055 | 0.00055 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.0016 | 0.0015 | notable |
| Other | 0.00083 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.;
Recessive Scores
- pRec
- 0.707
Intolerance Scores
- LoFtool
- 0.248
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.48
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.962
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |