TGM1

transglutaminase 1, the group of Transglutaminases

Basic information

Region (hg38): 14:24249114-24264432

Previous symbols: [ "ICR2" ]

Links

ENSG00000092295

∙ NCBI:7051 ∙ OMIM:190195 ∙ HGNC:11777 ∙ Uniprot:P22735 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive congenital ichthyosis 1 (Definitive), mode of inheritance: AR
autosomal recessive congenital ichthyosis 1 (Strong), mode of inheritance: AR
autosomal recessive congenital ichthyosis 1 (Strong), mode of inheritance: AR
lamellar ichthyosis (Supportive), mode of inheritance: AR
congenital non-bullous ichthyosiform erythroderma (Supportive), mode of inheritance: AR
bathing suit ichthyosis (Supportive), mode of inheritance: AR
self-healing collodion baby (Supportive), mode of inheritance: AR
acral self-healing collodion baby (Supportive), mode of inheritance: AR
autosomal recessive congenital ichthyosis 1 (Strong), mode of inheritance: AR
autosomal recessive congenital ichthyosis 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 1	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	7977373; 7824952; 7773290; 9326318; 9545389; 12542526; 18948357; 19486042; 19556108; 19863506; 20064174; 20301593; 22435431

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TGM1 gene.

not_provided (814 variants)
Autosomal_recessive_congenital_ichthyosis_1 (424 variants)
Inborn_genetic_diseases (116 variants)
Lamellar_ichthyosis (30 variants)
not_specified (29 variants)
TGM1-related_disorder (27 variants)
Abnormality_of_the_skin (5 variants)
Congenital_ichthyosiform_erythroderma (2 variants)
Autosomal_recessive_congenital_ichthyosis (1 variants)
Treacher_Collins_syndrome_1 (1 variants)
Ichthyosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000359.3. 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	1 clinvar	1 clinvar	16 clinvar	363 clinvar	6 clinvar	387
missense	30 clinvar	75 clinvar	199 clinvar	44 clinvar	5 clinvar	353
nonsense	32 clinvar	21 clinvar	1 clinvar			54
start loss			1			1
frameshift	47 clinvar	51 clinvar	1 clinvar			99
splice donor/acceptor (+/-2bp)	12 clinvar	25 clinvar				37
Total	122	173	218	407	11

Highest pathogenic variant AF is 0.00051147246

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGM1	protein_coding	protein_coding	ENST00000206765	14	15319

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.25e-13	0.837	125600	0	148	125748	0.000589

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0602	501	497	1.01	0.0000355	5289
Missense in Polyphen		212	236.58	0.8961		2541
Synonymous	-2.13	234	196	1.19	0.0000138	1685
Loss of Function	1.90	26	38.8	0.670	0.00000233	403

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000901	0.000898
Ashkenazi Jewish	0.000695	0.000695
East Asian	0.000109	0.000109
Finnish	0.000188	0.000185
European (Non-Finnish)	0.000905	0.000897
Middle Eastern	0.000109	0.000109
South Asian	0.000294	0.000294
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Responsible for cross- linking epidermal proteins during formation of the stratum corneum. Involved in cell proliferation (PubMed:26220141). {ECO:0000269|PubMed:26220141}.;
Disease: DISEASE: Ichthyosis, congenital, autosomal recessive 1 (ARCI1) [MIM:242300]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:11251583, ECO:0000269|PubMed:11511296, ECO:0000269|PubMed:19890349, ECO:0000269|PubMed:26220141, ECO:0000269|PubMed:7773290, ECO:0000269|PubMed:7824952, ECO:0000269|PubMed:9326318}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Recessive Scores

pRec: 0.476

Intolerance Scores

loftool: 0.118
rvis_EVS: -0.06
rvis_percentile_EVS: 48.93

Haploinsufficiency Scores

pHI: 0.294
hipred: N
hipred_score: 0.432
ghis: 0.437

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.332

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tgm1
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;

Gene ontology

Biological process: cellular protein modification process;positive regulation of keratinocyte proliferation;peptide cross-linking;keratinocyte differentiation;cell envelope organization;positive regulation of cell cycle;cornification
Cellular component: cornified envelope;cytosol;plasma membrane;intrinsic component of membrane;extracellular exosome
Molecular function: protein-glutamine gamma-glutamyltransferase activity;protein binding;metal ion binding