TGM6 (transglutaminase 6)

Gene

• Entrez ID: 343641
• Gene name: Transglutaminase 6
• Gene symbol: TGM6
• Synonyms (NCBI Gene): SCA35, TG6, TGM3L, TGY, dJ734P14.3
• Chromosome: 20
• Chromosome location: 20p13
• 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). Alte

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs141258102	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, synonymous variant
rs201964784	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs372250159	C>T	Pathogenic	Coding sequence variant, missense variant
rs377479985	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, 3 prime UTR variant
rs387907097	T>G	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs387907098	A>G,T	Pathogenic	Coding sequence variant, missense variant
rs793888526	AGA>-	Pathogenic	Coding sequence variant, inframe deletion
rs1181987535	->TCTCTGGCGTGACGACCTCCTG	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555799865	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555799867	->C	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555799870	TGCACAGGTA>-	Likely-pathogenic	Intron variant, coding sequence variant, splice donor variant
rs1599953368	G>A	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1421902	hsa-miR-149	CLIP-seq
MIRT1421903	hsa-miR-3190	CLIP-seq
MIRT1421904	hsa-miR-4491	CLIP-seq
MIRT1421905	hsa-miR-4649-3p	CLIP-seq
MIRT1421906	hsa-miR-4657	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003810	Function	Protein-glutamine gamma-glutamyltransferase activity	IBA
GO:0003810	Function	Protein-glutamine gamma-glutamyltransferase activity	IDA	23206699
GO:0003810	Function	Protein-glutamine gamma-glutamyltransferase activity	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	23206699, 25253745, 29053796
GO:0005737	Component	Cytoplasm	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016746	Function	Acyltransferase activity	IEA
GO:0046872	Function	Metal ion binding	IEA

Other IDs

• MIM: 613900
• HGNC: 16255
• e!Ensembl: ENSG00000166948

Protein

• UniProt ID: O95932
• Protein name: Protein-glutamine gamma-glutamyltransferase 6 (EC 2.3.2.13) (Transglutaminase Y) (TGY) (TGase Y) (Transglutaminase-3-like) (TGase-3-like) (Transglutaminase-6) (TG6) (TGase-6)
• Protein function: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00868	Transglut_N	3 → 119	Transglutaminase family	Domain
  PF01841	Transglut_core	252 → 357	Transglutaminase-like superfamily	Family
  PF00927	Transglut_C	495 → 600	Transglutaminase family, C-terminal ig like domain	Domain
  PF00927	Transglut_C	607 → 704	Transglutaminase family, C-terminal ig like domain	Domain

• Sequence:

  MAGIRVTKVDWQRSRNGAAHHTQEYPCPELVVRRGQSFSLTLELSRALDCEEILIFTMET
  GPRASEALHTKAVFQTSELERGEGWTAAREAQMEKTLTVSLASPPSAVIGRYLLSIRLSS
  HRKHSNRRLGEFVLLFNPWCAEDDVFLASEEERQEYVLSDSGIIFRGVEKHIRAQGWNYG
  QFEEDILNICLSILDRSPGHQNNPATDVSCRHNPIYVTRVISAMVNSNNDRGVVQGQWQG
  KYGGGTSPLHWRGSVAILQKWLKGRYKPVKYGQCWVFAGVLCTVLRCLGIATRVVSNFNS
  AHDTDQNLSVDKYVDSFGRTLEDLTEDSMWNFHVWNESWFARQDLGPSYNGWQVLDATPQ
  EESEGVFRCGPASVTAIREGDVHLAHDGPFVFAEVNADYITWLWHEDESRERVYSNTKKI
  GRCISTKAVGSDSRVDITDLYKYPEGSRKERQVYSKAVNRLFGVEASGRRIWIRRAGGRC
  LWRDDLLEPATKPSIAGKFKVLEPPMLGHDLRLALCLANLTSRAQRVRVNLSGATILYTR
  KPVAEILHESHAVRLGPQEEKRIPITISYSKYKEDLTEDKKILLAAMCLVTKGEKLLVEK
  DITLEDFITIKVLGPAMVGVAVTVEVTVVNPLIERVKDCALMVEGSGLLQEQLSIDVPTL
  EPQERASVQFDITPSKSGPRQLQVDLVSPHFPDIKGFVIVHVATAK

• Sequence length: 706

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Spinocerebellar ataxia type 35	Likely pathogenic; Pathogenic	rs750743855, rs766605124, rs2122376594, rs372250159, rs793888526	RCV001327983 RCV001849201 RCV001730101 RCV000170474 RCV000170475	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TGM6-related disorder	Likely pathogenic	rs1026525677	RCV003410753	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA, SPINOCEREBELLAR	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal dominant cerebellar ataxia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Axial muscle stiffness	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myopathic facies	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Oculomotor apraxia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson disease	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinsonian disorder	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSONIAN DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polyneuropathy	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Rigidity	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 35	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIAS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vascular parkinsonism	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer`s Disease	Alzheimer disease	GWASDB_DG	23535033		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	23535033		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	25867286		★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	33160304	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	BEFREE	21106500, 22554020		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	29072974		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune disease	Pubtator	28542044	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	30885888		★☆☆☆☆ Found in Text Mining only
Brain atrophy	Brain atrophy	BEFREE	30885888		★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	BEFREE	25867286, 28542044, 30885888		★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	Pubtator	28542044	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Ataxia	Cerebellar ataxia	Pubtator	33160304	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	33160304	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	BEFREE	30885888		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	30884206	Associate	★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	31698178		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Diseases	Gastrointestinal disease	Pubtator	28542044	Associate	★☆☆☆☆ Found in Text Mining only
Gluten intolerance	Gluten intolerance	BEFREE	18825674		★☆☆☆☆ Found in Text Mining only
Inherited acute myeloid leukemia	Myeloid Leukemia	ORPHANET_DG	24755948		★☆☆☆☆ Found in Text Mining only
Inherited acute myeloid leukemia	Myeloid Leukemia	Orphanet			★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	24755948		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	28273770		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis, Relapsing-Remitting	Multiple Sclerosis	BEFREE	28273770		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	18825674		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	28886934, 31698178		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	32259886	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease Secondary	Secondary parkinson disease	Pubtator	32259886	Associate	★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pseudobulbar Palsy	Pseudobulbar Palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
SPINOCEREBELLAR ATAXIA 31 (disorder)	Spinocerebellar Ataxia	BEFREE	22287014		★☆☆☆☆ Found in Text Mining only
SPINOCEREBELLAR ATAXIA 35	Spinocerebellar Ataxia	UNIPROT_DG	21106500, 22554020, 23206699, 25253745, 29053796		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 35	Spinocerebellar Ataxia	CLINVAR_DG	21106500		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 35	Spinocerebellar Ataxia	GENOMICS_ENGLAND_DG	22554020		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 35	Spinocerebellar Ataxia	BEFREE	23206699, 25253745, 28934387, 30229425, 30670339		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINOCEREBELLAR ATAXIA 35	Spinocerebellar Ataxia	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spinocerebellar Ataxia Type 1	Spinocerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 2	Spinocerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar ataxia type 35	Spinocerebellar Ataxia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Spinocerebellar Ataxia Type 4	Spinocerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 5	Spinocerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 6 (disorder)	Spinocerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 7	Spinocerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxias	Spinocerebellar ataxia	Pubtator	30229425, 32259886, 33160304, 34298918	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Supranuclear Palsy Progressive	Progressive supranuclear palsy	Pubtator	34298918	Associate	★☆☆☆☆ Found in Text Mining only