TGM5

transglutaminase 5, the group of Transglutaminases

Basic information

Region (hg38): 15:43232589-43266928

Links

ENSG00000104055 ∙ NCBI:9333 ∙ OMIM:603805 ∙ HGNC:11781 ∙ Uniprot:O43548 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acral peeling skin syndrome (Strong), mode of inheritance: AR
• acral peeling skin syndrome (Strong), mode of inheritance: AR
• acral peeling skin syndrome (Strong), mode of inheritance: AR
• acral peeling skin syndrome (Strong), mode of inheritance: AR
• acral peeling skin syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peeling skin syndrome 2	AR	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	Dermatologic	16380904

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TGM5 gene.

• not provided (5 variants)
• Acral peeling skin syndrome (3 variants)
• Inborn genetic diseases (2 variants)
• Peeling skin syndrome 1 (1 variants)
• TGM5-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGM5 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			7	5	5	17
missense	3	1	57	9	9	79
nonsense	1	2	1			4
start loss						0
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			2		2	4
non coding			8	1	11	20
Total	7	7	74	15	25

Highest pathogenic variant AF is 0.00242

Variants in TGM5

This is a list of pathogenic ClinVar variants found in the TGM5 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-43232681-T-C		Acral peeling skin syndrome	Uncertain significance (Jan 13, 2018)
15-43232761-G-A		Acral peeling skin syndrome	Uncertain significance (Jan 13, 2018)
15-43232939-G-A		Acral peeling skin syndrome	Benign (Jan 12, 2018)
15-43233135-A-G		Acral peeling skin syndrome	Uncertain significance (Jan 13, 2018)
15-43233193-A-G		Acral peeling skin syndrome	Likely pathogenic (Mar 29, 2024)
15-43233225-C-T		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
15-43233316-C-T		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
15-43233344-G-T		Inborn genetic diseases	Likely benign (Jan 04, 2022)
15-43233553-C-T			Uncertain significance (Oct 06, 2023)
15-43233577-G-A			Benign (May 24, 2018)
15-43233593-A-G		Acral peeling skin syndrome	Benign (Apr 01, 2024)
15-43233607-G-T		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
15-43233622-C-T		Acral peeling skin syndrome	Uncertain significance (Jan 13, 2018)
15-43233623-G-A		Inborn genetic diseases	Uncertain significance (Jul 06, 2022)
15-43233641-A-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
15-43233672-C-G		Acral peeling skin syndrome • Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
15-43233672-C-T		Inborn genetic diseases	Likely benign (Jan 26, 2022)
15-43234776-G-A		Acral peeling skin syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 23, 2022)
15-43234822-T-C		Acral peeling skin syndrome	Benign (Jan 12, 2018)
15-43234824-T-G		Acral peeling skin syndrome	Benign/Likely benign (Apr 01, 2024)
15-43234825-C-T		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
15-43234829-ACTGC-TGAAGGA		Acral peeling skin syndrome	Pathogenic (Oct 01, 2012)
15-43234871-G-A		Acral peeling skin syndrome • TGM5-related disorder	Benign/Likely benign (Dec 15, 2023)
15-43234894-A-G		Acral peeling skin syndrome	Uncertain significance (Jan 13, 2018)
15-43234928-T-C		Acral peeling skin syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGM5	protein_coding	protein_coding	ENST00000220420	13	34263

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.42e-25	0.000110	125570	0	178	125748	0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.316	403	386	1.05	0.0000236	4754
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00141	0.00141
Ashkenazi Jewish	0.00229	0.00228
East Asian	0.00120	0.00120
Finnish	0.000371	0.000370
European (Non-Finnish)	0.000686	0.000686
Middle Eastern	0.00120	0.00120
South Asian	0.000359	0.000359
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.195
• hipred: N
• hipred_score: 0.296
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0950

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tgm5

Gene ontology

• Biological process: cellular protein modification process;epidermis development;peptide cross-linking;cornification
• Cellular component: cytoplasm;plasma membrane
• Molecular function: protein-glutamine gamma-glutamyltransferase activity;metal ion binding