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

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 (90 variants)
• Autosomal recessive congenital ichthyosis 1 (46 variants)
• Lamellar ichthyosis (8 variants)
• TGM1-related disorder (2 variants)
• Autosomal recessive congenital ichthyosis (1 variants)
• Abnormality of the skin (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.

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				341	8	349
missense	22	51	81	17	3	174
nonsense	27	22	1			50
start loss			1			1
frameshift	42	40	1			83
inframe indel	3	2	4	1		10
splice donor/acceptor (+/-2bp)	11	24				35
splice region			2	45	3	50
non coding			5	119	15	139
Total	105	139	93	478	26

Highest pathogenic variant AF is 0.000276

Variants in TGM1

This is a list of pathogenic ClinVar variants found in the TGM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-24249149-C-T		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Jan 12, 2018)
14-24249151-G-T		Autosomal recessive congenital ichthyosis 1	Likely benign (Jan 13, 2018)
14-24249173-TCTCCGGGAGCCCTGGACTCCCC-T			Benign (Jun 19, 2021)
14-24249223-A-G		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Jan 13, 2018)
14-24249309-G-A		Autosomal recessive congenital ichthyosis 1	Benign (Sep 10, 2021)
14-24249311-G-A		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Apr 17, 2020)
14-24249319-T-C			Likely benign (Dec 29, 2021)
14-24249322-A-G			Likely benign (Feb 21, 2023)
14-24249326-C-G		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Apr 17, 2020)
14-24249327-G-A		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Dec 01, 2017)
14-24249328-A-G		Autosomal recessive congenital ichthyosis 1	Likely benign (Jan 22, 2024)
14-24249331-T-C			Likely benign (Jan 30, 2024)
14-24249337-A-G			Likely benign (Jan 18, 2024)
14-24249347-TCTC-T		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Jan 26, 2017)
14-24249358-A-G			Likely benign (Sep 10, 2023)
14-24249362-T-A		Autosomal recessive congenital ichthyosis 1	Benign/Likely benign (Jan 25, 2024)
14-24249364-A-T			Likely benign (Oct 04, 2023)
14-24249366-C-A			Uncertain significance (Mar 04, 2022)
14-24249369-C-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2022)
14-24249373-G-A		Autosomal recessive congenital ichthyosis 1	Likely benign (Jan 26, 2024)
14-24249385-G-GC		Autosomal recessive congenital ichthyosis 1	Uncertain significance (Aug 04, 2017)
14-24249390-C-T		Autosomal recessive congenital ichthyosis 1 • Inborn genetic diseases	Likely benign (Jan 09, 2024)
14-24249391-A-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
14-24249417-C-A		Autosomal recessive congenital ichthyosis 1	Uncertain significance (-)
14-24249421-G-A			Likely benign (Jun 09, 2022)

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