TGM5
protein-codingtransglutaminase 5, the group of Transglutaminases
Gene summary
This gene encodes a member of the transglutaminase family. The encoded protein catalyzes formation of protein cross-links between glutamine and lysine residues, often resulting in stabilization of protein assemblies. This reaction is calcium dependent. Mutations in this gene have been associated with acral peeling skin syndrome. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012345
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012345
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0012345
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0012345
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012345
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0012345
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TGM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_201631.4. 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 | 9 | 7 | 4 | 20 | ||
| missense | 3 | 5 | 117 | 15 | 8 | 148 |
| nonsense | 2 | 3 | 5 | |||
| start loss | 0 | |||||
| frameshift | 3 | 3 | 1 | 7 | ||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 1 | 5 | ||
| Total | 9 | 14 | 128 | 22 | 12 | 185 |
Highest pathogenic variant AF is 0.0028188385
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_963925.2 | 13 | MANE Select | |
| Ensembl | ENSP00000220420.5 | 13 | MANE Select | |
| RefSeq | NP_004236.1 | 12 | Standard | |
| Ensembl | ENSP00000220419.8 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cellular protein modification process
- epidermis development
- peptide cross-linking
- cornification
Molecular Function
- protein-glutamine gamma-glutamyltransferase activity
- metal ion binding
Cellular Component
- cytoplasm
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000220420
- Coding exons
- 13
- Length
- 34263
- Individuals with no LoFs
- 125570
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 178
- Defined
- 125748
- p
- 0.000708
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.316 | 403 | 386 | 1.05 | 0.0000236 | 4754 |
| Missense (PolyPhen) | 164 | 166.73 | 0.98364 | 2144 | ||
| Synonymous | 0.689 | 149 | 160 | 0.931 | 0.0000104 | 1379 |
| Loss of Function | -0.465 | 36 | 33.1 | 1.09 | 0.00000154 | 383 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00080 | 0.00080 | rare |
| Latino/Admixed American | 0.00061 | 0.00061 | rare |
| Ashkenazi Jewish | 0.0023 | 0.0023 | notable |
| East Asian | 0.0012 | 0.0012 | notable |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00069 | 0.00069 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Contributes to the formation of the cornified cell envelope of keratinocytes.;
- Disease
- DISEASE: Peeling skin syndrome 2 (PSS2) [MIM:609796]: A non- inflammatory and localized form of peeling skin syndrome, a genodermatosis characterized by the continuous shedding of the outer layers of the epidermis. In PSS2 patients, skin peeling is painless and strictly limited to the dorsa of the hands and feet. It is accompanied by painless erythema and spontaneous non- scarring healing. Ultrastructural and histological analysis shows a level of blistering high in the epidermis at the stratum granulosum-stratum corneum junction. {ECO:0000269|PubMed:16380904}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.226
- RVIS EVS
- 0.83
- RVIS percentile EVS
- 88.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0950
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |