TGM5

transglutaminase 5, the group of Transglutaminases

Basic information

Region (hg38): 15:43232590-43266928

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
acral peeling skin syndrome (Definitive), 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.

Inborn_genetic_diseases (98 variants)
Acral_peeling_skin_syndrome (69 variants)
not_provided (55 variants)
TGM5-related_disorder (16 variants)
Peeling_skin_syndrome_1 (3 variants)
not_specified (2 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. These statistics are base on transcript: NM_000201631.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			10 clinvar	7 clinvar	4 clinvar	21
missense	4 clinvar	4 clinvar	111 clinvar	14 clinvar	8 clinvar	141
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift	3 clinvar	2 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	1 clinvar			5
Total	9	11	123	21	12

Highest pathogenic variant AF is 0.0028188385

Loading clinvar variants...

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
Phenotype

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