GeneBe

TGM1

protein-coding

transglutaminase 1, the group of Transglutaminases

Gene summary

The protein encoded by this gene is a membrane protein that catalyzes the addition of an alkyl group from an akylamine to a glutamine residue of a protein, forming an alkylglutamine in the protein. This protein alkylation leads to crosslinking of proteins and catenation of polyamines to proteins. This gene contains either one or two copies of a 22 nt repeat unit in its 3' UTR. Mutations in this gene have been associated with autosomal recessive lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). [provided by RefSeq, Jul 2008]

Previous symbols:
  • ICR2

MANE transcript

NM_000359.3

Inheritance

AR

ClinVar variants

P:311U:245B:421

Top phenotype

Ichthyosis, congenital, autosomal recessive 1

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr14:24,249,114-24,264,432

External References & Databases

Ensembl (ENSG00000092295)NCBI Gene (7051)OMIM (190195)HGNC:11777GenCCUniProt (P22735)AlphaFoldClinVar (TGM1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~15.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

bathing suit ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015085

Submitter: Orphanet

self-healing collodion babySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017267

Submitter: Orphanet

acral self-healing collodion babySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017268

Submitter: Orphanet

autosomal recessive congenital ichthyosis 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009441

Submitter: Natera

autosomal recessive congenital ichthyosis 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009441

Submitter: G2P

autosomal recessive congenital ichthyosis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009441

Submitter: Genomics England PanelApp

lamellar ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017778

Submitter: Orphanet

autosomal recessive congenital ichthyosis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009441

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive congenital ichthyosis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009441

Submitter: PanelApp Australia

congenital non-bullous ichthyosiform erythrodermaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019306

Submitter: Orphanet

autosomal recessive congenital ichthyosis 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009441

Submitter: Myriad Women's Health

Clinical Genomic Database (CGD)

Ichthyosis, congenital, autosomal recessive 1AR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 7977373; 7824952; 7773290; 9326318; 9545389; 12542526; 18948357; 19486042; 19556108; 19863506; 20064174; 20301593; 22435431Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TGM1 variants in ClinVar

14 Conditions Cataloged
not providedTotal: 826
Autosomal recessive congenital ichthyosis 1Total: 439
Inborn genetic diseasesTotal: 134
Lamellar ichthyosisTotal: 34
not specifiedTotal: 29
TGM1-related disorderTotal: 27
Abnormality of the skinTotal: 5
Ichthyosis and erythrokeratodermaTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000359.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
19
clinvar
365
clinvar
6
clinvar
 392
missense
28
clinvar
86
clinvar
218
clinvar
45
clinvar
5
clinvar
 382
nonsense
32
clinvar
23
clinvar
1
clinvar
 56
start loss
1
clinvar
 1
frameshift
46
clinvar
56
clinvar
2
clinvar
 104
splice donor/acceptor (+/-2bp)
14
clinvar
24
clinvar
4
clinvar
 42
Total12119024541011977

Highest pathogenic variant AF is 0.00051147246

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000359.3RefSeqNP_000350.114MANE Select
ENST00000206765.11EnsemblENSP00000206765.614MANE Select
ENST00000544573.5EnsemblENSP00000439446.17Standard
ENST00000544573.6EnsemblENSP00000439446.17Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Keratinization
  • Developmental Biology
  • Formation of the cornified envelope

Biological Process

  • cellular protein modification process
  • positive regulation of keratinocyte proliferation
  • peptide cross-linking
  • keratinocyte differentiation
  • cell envelope organization

Molecular Function

  • protein-glutamine gamma-glutamyltransferase activity
  • protein binding
  • metal ion binding

Cellular Component

  • cornified envelope
  • cytosol
  • plasma membrane
  • intrinsic component of membrane
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000206765
Coding exons
14
Length
15319
Individuals with no LoFs
125600
Homozygous LoFs
0
Heterozygous LoFs
148
Defined
125748
p
0.000589
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.06025014971.010.00003555289
Missense (PolyPhen)212236.580.89612541
Synonymous-2.132341961.190.00001381685
Loss of Function1.902638.80.6700.00000233403

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000500.00049rare
Latino/Admixed American0.000410.00040rare
Ashkenazi Jewish0.000690.00069rare
East Asian0.000110.00011rare
Finnish0.000190.00018rare
European (Non-Finnish)0.000910.00090rare
South Asian0.000290.00029rare
Other0.000330.00033rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.476

Intolerance Scores

LoFtool
0.118
RVIS EVS
-0.06
RVIS percentile EVS
48.93

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.332

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.