TGM6
protein-codingtransglutaminase 6, the group of Transglutaminases
Gene summary
The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
- TGM3L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~51.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013485
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0013485
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0013485
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0013485
Submitter: Illumina
Inheritance Pattern: AD
Disease ID:MONDO:0013485
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
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 TGM6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198994.3. 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 | 6 | 81 | 10 | 97 | ||
| missense | 3 | 231 | 67 | 9 | 310 | |
| nonsense | 5 | 5 | 3 | 1 | 14 | |
| start loss | 0 | |||||
| frameshift | 1 | 4 | 10 | 4 | 19 | |
| splice donor/acceptor (+/-2bp) | 1 | 3 | 9 | 2 | 15 | |
| Total | 2 | 15 | 261 | 157 | 20 | 455 |
Highest pathogenic variant AF is 0.0004827499
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_945345.2 | 13 | MANE Select | |
| Ensembl | ENSP00000202625.2 | 13 | MANE Select | |
| RefSeq | NP_001241663.1 | 12 | Standard | |
| Ensembl | ENSP00000370831.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- peptide cross-linking
Molecular Function
- protein-glutamine gamma-glutamyltransferase activity
- metal ion binding
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000202625
- Coding exons
- 13
- Length
- 51846
- Individuals with no LoFs
- 125293
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 454
- Defined
- 125748
- p
- 0.00181
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.820 | 470 | 423 | 1.11 | 0.0000284 | 4585 |
| Missense (PolyPhen) | 174 | 139.83 | 1.2444 | 1657 | ||
| Synonymous | -0.321 | 184 | 179 | 1.03 | 0.0000131 | 1420 |
| Loss of Function | -0.190 | 36 | 34.8 | 1.03 | 0.00000188 | 366 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00055 | rare |
| Latino/Admixed American | 0.0010 | 0.00072 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0021 | 0.0021 | notable |
| Finnish | 0.0042 | 0.0041 | notable |
| European (Non-Finnish) | 0.0021 | 0.0015 | notable |
| South Asian | 0.0038 | 0.0037 | notable |
| Other | 0.0023 | 0.0021 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. {ECO:0000250}.;
- Disease
- DISEASE: Spinocerebellar ataxia 35 (SCA35) [MIM:613908]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA35 patients commonly show upper limb involvement and torticollis. There is no cognitive impairment. {ECO:0000269|PubMed:21106500, ECO:0000269|PubMed:22554020, ECO:0000269|PubMed:23206699, ECO:0000269|PubMed:25253745, ECO:0000269|PubMed:29053796}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.137
- RVIS EVS
- 1.63
- RVIS percentile EVS
- 96.08
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.204
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |