TGM5 (transglutaminase 5)

Gene

• Entrez ID: 9333
• Gene name: Transglutaminase 5
• Gene symbol: TGM5
• Synonyms (NCBI Gene): PSS2, TG(X), TGASE5, TGASEX, TGM6, TGMX, TGX
• Chromosome: 15
• Chromosome location: 15q15.2
• 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. Mu

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs112292549	C>A	Pathogenic	Missense variant, genic upstream transcript variant, intron variant, coding sequence variant
rs115677373	A>G	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant
rs143601447	A>G	Likely-pathogenic, pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant
rs606231276	C>G	Pathogenic	Coding sequence variant, missense variant
rs606231277	G>-	Pathogenic	Genic upstream transcript variant, frameshift variant, coding sequence variant
rs606231278	ACTGC>TGAAGGA	Pathogenic	Frameshift variant, coding sequence variant
rs748610718	AC>-	Pathogenic	Splice donor variant, intron variant, upstream transcript variant, genic upstream transcript variant
rs749224503	C>G,T	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs755087362	C>T	Likely-pathogenic	Splice donor variant, genic upstream transcript variant
rs758505358	T>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs777586604	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs778322388	G>-	Pathogenic, likely-pathogenic	Intron variant, frameshift variant, genic upstream transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1421896	hsa-miR-1264	CLIP-seq
MIRT1421897	hsa-miR-3157-3p	CLIP-seq
MIRT1421898	hsa-miR-4290	CLIP-seq
MIRT1421899	hsa-miR-4633-3p	CLIP-seq
MIRT1421900	hsa-miR-490-5p	CLIP-seq
MIRT1421901	hsa-miR-874	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	IEA
GO:0003810	Function	Protein-glutamine gamma-glutamyltransferase activity	TAS	9452468
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0008544	Process	Epidermis development	TAS	9452468
GO:0016740	Function	Transferase activity	IEA
GO:0016746	Function	Acyltransferase activity	IEA
GO:0036211	Process	Protein modification process	TAS	9452468
GO:0046872	Function	Metal ion binding	IEA

Other IDs

• MIM: 603805
• HGNC: 11781
• e!Ensembl: ENSG00000104055

Protein

• UniProt ID: O43548
• Protein name: Protein-glutamine gamma-glutamyltransferase 5 (EC 2.3.2.13) (Transglutaminase X) (TG(X)) (TGX) (TGase X) (Transglutaminase-5) (TGase-5)
• Protein 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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00868	Transglut_N	4 → 122	Transglutaminase family	Domain
  PF01841	Transglut_core	245 → 361	Transglutaminase-like superfamily	Family
  PF00927	Transglut_C	507 → 606	Transglutaminase family, C-terminal ig like domain	Domain
  PF00927	Transglut_C	620 → 718	Transglutaminase family, C-terminal ig like domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in foreskin keratinocytes.
• Sequence:

  MAQGLEVALTDLQSSRNNVRHHTEEITVDHLLVRRGQAFNLTLYFRNRSFQPGLDNIIFV
  VETGPLPDLALGTRAVFSLARHHSPSPWIAWLETNGATSTEVSLCAPPTAAVGRYLLKIH
  IDSFQGSVTAYQLGEFILLFNPWCPEDAVYLDSEPQRQEYVMNDYGFIYQGSKNWIRPCP
  WNYGQFEDKIIDICLKLLDKSLHFQTDPATDCALRGSPVYVSRVVCAMINSNDDNGVLNG
  NWSENYTDGANPAEWTGSVAILKQWNATGCQPVRYGQCWVFAAVMCTVMRCLGIPTRVIT
  NFDSGHDTDGNLIIDEYYDNTGRILGNKKKDTIWNFHVWNECWMARKDLPPAYGGWQVLD
  ATPQEMSNGVYCCGPASVRAIKEGEVDLNYDTPFVFSMVNADCMSWLVQGGKEQKLHQDT
  SSVGNFISTKSIQSDERDDITENYKYEEGSLQERQVFLKALQKLKARSFHGSQRGAELQP
  SRPTSLSQDSPRSLHTPSLRPSDVVQVSLKFKLLDPPNMGQDICFVLLALNMSSQFKDLK
  VNLSAQSLLHDGSPLSPFWQDTAFITLSPKEAKTYPCKISYSQYSQYLSTDKLIRISALG
  EEKSSPEKILVNKIITLSYPSITINVLGAAVVNQPLSIQVIFSNPLSEQVEDCVLTVEGS
  GLFKKQQKVFLGVLKPQHQASIILETVPFKSGQRQIQANMRSNKFKDIKGYRNVYVDFAL
  

• Sequence length: 720

Pathways

Reactome:

Formation of the cornified envelope

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
Acral peeling skin syndrome	Likely pathogenic; Pathogenic	rs755448082, rs1045182796, rs115677373, rs606231277, rs606231278, rs2142390360, rs112292549, rs2542636329, rs1451315165, rs748610718, rs778322388	RCV001783866 RCV001783867 RCV000144912 RCV000144914 RCV000144915 RCV002249190 RCV000006411 RCV003445428 RCV003989429 RCV005632417 RCV000778431	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Peeling skin syndrome 1	Pathogenic; Likely pathogenic	rs606231277, rs755087362	RCV000989297 RCV000989296	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
TGM5-related disorder	Pathogenic	rs112292549	RCV003398452	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEELING SKIN SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEELING SKIN SYNDROME 2	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEELING SKIN SYNDROME, ACRAL TYPE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acral peeling skin syndrome	Acral Peeling Skin Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Adrenogenital Syndrome	Adrenogenital Syndrome	BEFREE	31028847		★☆☆☆☆ Found in Text Mining only
alpha 1-Antitrypsin Deficiency	Alpha 1-Antitrypsin Deficiency	BEFREE	31028847		★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder	Attention Deficit Hyperactivity Disorder	BEFREE	27211562		★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder with Hyperactivity	Attention deficit hyperactivity disorder	Pubtator	27211562	Associate	★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	27211562		★☆☆☆☆ Found in Text Mining only
Cholesteatoma	Cholesteatoma	BEFREE	27390311		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	27211562		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	BEFREE	31028847		★☆☆☆☆ Found in Text Mining only
Congenital ichthyosis	Congenital Ichthyosis	BEFREE	12230511		★☆☆☆☆ Found in Text Mining only
Darier Disease	Darier disease	Pubtator	12230511	Associate	★☆☆☆☆ Found in Text Mining only
Dermatitis, Atopic	Dermatitis	BEFREE	23189155		★☆☆☆☆ Found in Text Mining only
Dermatologic disorders	Dermatologic Disorders	BEFREE	16380904		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	27211562		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	BEFREE	23189155		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa	Epidermolysis Bullosa	BEFREE	28940785		★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa Simplex	Epidermolysis Bullosa Simplex	BEFREE	24628291		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	29048665		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	29048665		★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	BEFREE	12230511		★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	LHGDN	12230511		★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyosis	Ichthyosis	Pubtator	12230511	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyosis Vulgaris	Ichthyosis Vulgaris	BEFREE	12230511		★☆☆☆☆ Found in Text Mining only
Ichthyosis Vulgaris	Ichthyosis vulgaris	Pubtator	12230511	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	27211562		★☆☆☆☆ Found in Text Mining only
Keratoconus	Keratoconus	Pubtator	36240204	Associate	★☆☆☆☆ Found in Text Mining only
Keratosis Follicularis	Keratosis Follicularis	BEFREE	12230511		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	21303977, 24518713, 37058478	Associate	★☆☆☆☆ Found in Text Mining only
Nasal Polyps	Nasal polyp	Pubtator	36361742	Associate	★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	24518713		★☆☆☆☆ Found in Text Mining only
Peeling Skin Syndrome	Peeling skin syndrome	Pubtator	16380904, 21307953, 22429841	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEELING SKIN SYNDROME	Peeling Skin Syndrome	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peeling skin syndrome acral type	Peeling skin syndrome	Pubtator	16380904, 21307953, 22429841, 22622422	Associate	★☆☆☆☆ Found in Text Mining only
Peeling skin syndrome, acral type	Peeling skin syndrome	BEFREE	16380904, 22622422, 24628291, 25644735, 26684698		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peeling skin syndrome, acral type	Peeling skin syndrome	CLINVAR_DG	16380904, 20164844, 22036214, 22622422, 24019772, 24628291, 25644735, 26707537, 29242947		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peeling skin syndrome, acral type	Peeling skin syndrome	UNIPROT_DG	16380904		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peeling skin syndrome, acral type	Peeling skin syndrome	GENOMICS_ENGLAND_DG	22036214, 22622422		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peeling skin syndrome, acral type	Peeling skin syndrome	ORPHANET_DG	9767297		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peeling skin syndrome, acral type	Peeling skin syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polyglucosan Body Disease, Adult Form	Polyglucosan body myopathy	BEFREE	28630259		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	BEFREE	12230511, 19554025		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	Pubtator	12230511, 19554025	Associate	★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychotic disorders	Pubtator	27211562	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	26091878		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	27211562	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	31028847		★☆☆☆☆ Found in Text Mining only
Skin Diseases	Skin disease	Pubtator	16380904	Associate	★☆☆☆☆ Found in Text Mining only
Skin Erosion	Skin Erosion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uncombable hair syndrome	Uncombable Hair Syndrome	BEFREE	28940785		★☆☆☆☆ Found in Text Mining only
Very long chain acyl-CoA dehydrogenase deficiency	Acyl CoA Dehydrogenase Deficiency	BEFREE	31028847		★☆☆☆☆ Found in Text Mining only
von Willebrand Disease, Type 2N	Von Willebrand Disorder	BEFREE	31028847		★☆☆☆☆ Found in Text Mining only