TGM6

transglutaminase 6, the group of Transglutaminases

Basic information

Region (hg38): 20:2380900-2432753

Previous symbols: [ "TGM3L" ]

Links

ENSG00000166948 ∙ NCBI:343641 ∙ OMIM:613900 ∙ HGNC:16255 ∙ Uniprot:O95932 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 35 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 35 (Moderate), mode of inheritance: AD
• spinocerebellar ataxia type 35 (Limited), mode of inheritance: AD
• spinocerebellar ataxia type 35 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 35	AD	General	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	Neurologic	21106500; 22554020

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TGM6 gene.

• not provided (289 variants)
• Spinocerebellar ataxia type 35 (100 variants)
• not specified (74 variants)
• Inborn genetic diseases (39 variants)
• TGM6-related condition (3 variants)
• Autosomal dominant cerebellar ataxia (1 variants)
• Axial muscle stiffness;Oculomotor apraxia;Myopathic facies;Rigidity;Parkinsonism (1 variants)
• Polyneuropathy (1 variants)
• Acute myeloid leukemia (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGM6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	44	14	64
missense		1	118	33	16	168
nonsense		1	3	1	1	6
start loss						0
frameshift			11	1		12
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	1	2	6	1		10
splice region			3	2	3	8
non coding			11	16	46	73
Total	1	4	156	97	77

Highest pathogenic variant AF is 0.000112

Variants in TGM6

This is a list of pathogenic ClinVar variants found in the TGM6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-2380927-C-T		Spinocerebellar ataxia type 35	Likely benign (Jan 13, 2018)
20-2380933-T-C		Spinocerebellar ataxia type 35	Benign (Jan 13, 2018)
20-2380964-T-A		Spinocerebellar ataxia type 35	Uncertain significance (Jan 13, 2018)
20-2380967-A-G		Spinocerebellar ataxia type 35 • not specified	Benign/Likely benign (Jun 01, 2022)
20-2380976-G-T			Likely benign (Feb 01, 2023)
20-2380984-G-A		not specified	Benign (Oct 13, 2023)
20-2380984-G-T		not specified	Uncertain significance (May 01, 2017)
20-2381021-G-A			Likely benign (Jan 19, 2022)
20-2381038-C-T			Benign (Apr 13, 2021)
20-2381132-G-T			Likely benign (May 19, 2021)
20-2381148-G-A			Benign (May 15, 2021)
20-2381278-A-G			Benign (Apr 13, 2021)
20-2394454-AT-A		See cases	Uncertain significance (Mar 23, 2020)
20-2394456-C-G		Spinocerebellar ataxia type 35 • not specified • TGM6-related disorder	Benign/Likely benign (Nov 25, 2023)
20-2394464-C-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
20-2394475-T-G		Spinocerebellar ataxia type 35	Benign/Likely benign (Jan 01, 2024)
20-2394481-C-T		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
20-2394482-G-A		Spinocerebellar ataxia type 35 • TGM6-related disorder	Conflicting classifications of pathogenicity (Nov 22, 2023)
20-2394486-G-A		Spinocerebellar ataxia type 35 • not specified	Benign/Likely benign (Feb 01, 2024)
20-2394495-C-T			Likely benign (Jan 13, 2023)
20-2394495-CGCTGC-TGGGTACT			Uncertain significance (Nov 03, 2020)
20-2394496-G-A			Likely benign (Nov 19, 2022)
20-2394508-A-G		Spinocerebellar ataxia type 35	Uncertain significance (Feb 21, 2018)
20-2394518-AC-A			Uncertain significance (May 04, 2022)
20-2394519-C-T			Likely benign (Oct 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGM6	protein_coding	protein_coding	ENST00000202625	13	51846

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.12e-24	0.000270	125293	1	454	125748	0.00181

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.820	470	423	1.11	0.0000284	4585
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00163	0.00157
Ashkenazi Jewish	0.00	0.00
East Asian	0.00212	0.00207
Finnish	0.00421	0.00407
European (Non-Finnish)	0.00211	0.00148
Middle Eastern	0.00212	0.00207
South Asian	0.00376	0.00373
Other	0.00229	0.00212

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.112
• hipred: N
• hipred_score: 0.241
• ghis: 0.415

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.204

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tgm6
• Phenotype: skeleton phenotype; vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: peptide cross-linking
• Cellular component: cytoplasm
• Molecular function: protein-glutamine gamma-glutamyltransferase activity;metal ion binding