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GeneE
27 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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TGM1
transglutaminase 1
Chromosome 14 Β· 14q12
NCBI Gene: 7051Ensembl: ENSG00000092295.13HGNC: HGNC:11777UniProt: P22735
190PubMed Papers
1Diseases
0Drugs
299Pathogenic Variants
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein-glutamine gamma-glutamyltransferase activityprotein bindingidentical protein bindingpositive regulation of keratinocyte proliferationIchthyosis, congenital, autosomal recessive 1
✦AI Summary

TGM1 (transglutaminase 1) catalyzes protein cross-linking and polyamine conjugation, primarily functioning in epidermal barrier formation 123. It cross-links epidermal proteins during stratum corneum formation and promotes keratinocyte proliferation and differentiation 34. TGM1 is critical for cornified envelope assembly and maintaining skin barrier integrity 5. Mechanistically, TGM1 operates through transamidation reactions. Recent evidence reveals that TGM1 transamidates Exo70 with cystatin A, promoting tumor cell motility and extracellular matrix remodelingβ€”a process inhibited by the tumor suppressor LKB1 6. TGM1 expression is regulated by mitogen-activated protein kinase signaling pathways and associated with GF-RTK-PI3K and JAK-STAT signaling 7. Clinically, TGM1 mutations cause autosomal recessive congenital ichthyosis type 1 (ARCI), characterized by severe skin barrier dysfunction 8. TGM1 variants are associated with collodion membrane at birth, alopecia, hearing problems, and eye abnormalities in ichthyosis patients 9. Beyond monogenic disease, TGM1 functions as a signature gene in psoriasis, where elevated expression increases inflammatory cytokine production and keratinocyte differentiation markers 7. Pan-cancer analysis indicates TGM1 has prognostic significance and immunomodulatory roles in multiple malignancies 10. Gene therapy approaches using retroviral vectors effectively restore TGM1 expression in patient-derived keratinocytes, restoring barrier function 5.

Sources cited
1
TGM1 is critical for cornified envelope assembly and maintaining skin barrier integrity .
PMID: 39234443
2
Recent evidence reveals that TGM1 transamidates Exo70 with cystatin A, promoting tumor cell motility and extracellular matrix remodelingβ€”a process inhibited by the tumor suppressor LKB1 .
PMID: 39146185
3
TGM1 expression is regulated by mitogen-activated protein kinase signaling pathways and associated with GF-RTK-PI3K and JAK-STAT signaling .
PMID: 41268597
4
Clinically, TGM1 mutations cause autosomal recessive congenital ichthyosis type 1 (ARCI), characterized by severe skin barrier dysfunction .
PMID: 33435499
5
TGM1 variants are associated with collodion membrane at birth, alopecia, hearing problems, and eye abnormalities in ichthyosis patients .
PMID: 34851365
6
Pan-cancer analysis indicates TGM1 has prognostic significance and immunomodulatory roles in multiple malignancies .
PMID: 38472489
Disease Associationsβ“˜1
Ichthyosis, congenital, autosomal recessive 1UniProt
Pathogenic Variants299
NM_000359.3(TGM1):c.401A>G (p.Tyr134Cys)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 134
NM_000359.3(TGM1):c.968G>A (p.Arg323Gln)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Lamellar ichthyosis|Ichthyosis and erythrokeratoderma
β˜…β˜…β˜†β˜†2026β†’ Residue 323
NM_000359.3(TGM1):c.871G>A (p.Gly291Ser)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 291
NM_000359.3(TGM1):c.1223_1227del (p.Asp408fs)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 408
NM_000359.3(TGM1):c.1166G>A (p.Arg389His)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Abnormality of the skin|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2026β†’ Residue 389
NM_000359.3(TGM1):c.427C>T (p.Arg143Cys)Pathogenic
not provided|Autosomal recessive congenital ichthyosis 1
β˜…β˜…β˜†β˜†2026β†’ Residue 143
NM_000359.3(TGM1):c.425G>A (p.Arg142His)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Abnormality of the skin|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2026β†’ Residue 142
NM_000359.3(TGM1):c.877-2A>GPathogenic
not provided|Autosomal recessive congenital ichthyosis 1|Autosomal recessive congenital ichthyosis|TGM1-related disorder|Lamellar ichthyosis|Lung cancer|Familial cancer of breast|Cholangiocarcinoma|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2026
NM_000359.3(TGM1):c.1042C>T (p.Arg348Ter)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2026β†’ Residue 348
NM_000359.3(TGM1):c.857G>A (p.Arg286Gln)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|TGM1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 286
NM_000359.3(TGM1):c.919C>G (p.Arg307Gly)Pathogenic
not provided|Lamellar ichthyosis|Autosomal recessive congenital ichthyosis 1
β˜…β˜…β˜†β˜†2026β†’ Residue 307
NM_000359.3(TGM1):c.1160-2_1160-1delPathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2026
NM_000359.3(TGM1):c.376C>T (p.Arg126Cys)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 126
NM_000359.3(TGM1):c.1187G>A (p.Arg396His)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|TGM1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 396
NM_000359.3(TGM1):c.2278C>T (p.Arg760Ter)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 760
NM_000359.3(TGM1):c.1186C>T (p.Arg396Cys)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2025β†’ Residue 396
NM_000359.3(TGM1):c.1165C>T (p.Arg389Cys)Likely pathogenic
not provided|Autosomal recessive congenital ichthyosis 1
β˜…β˜…β˜†β˜†2025β†’ Residue 389
NM_000359.3(TGM1):c.1469A>G (p.Asp490Gly)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2025β†’ Residue 490
NM_000359.3(TGM1):c.984+1G>APathogenic
Autosomal recessive congenital ichthyosis 1|not provided
β˜…β˜…β˜†β˜†2025
NM_000359.3(TGM1):c.424C>T (p.Arg142Cys)Pathogenic
Autosomal recessive congenital ichthyosis 1|not provided|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2025β†’ Residue 142
View on ClinVar β†—
Related Genes
NIPAL4Protein interaction96%ABCA12Protein interaction95%CYP4F22Protein interaction92%ALOX12BProtein interaction91%ALOXE3Protein interaction90%PPLProtein interaction84%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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TGM1NIPAL4ABCA12CYP4F22ALOX12BALOXE3PPL
PROTEIN STRUCTURE
Preparing viewer…
PDB2XZZ Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.69 [0.56–0.85]
RankingsWhere TGM1 stands among ~20K protein-coding genes
  • #2,258of 20,598
    Most Researched190 Β· top quartile
  • #207of 5,498
    Most Pathogenic Variants299 Β· top 5%
  • #7,317of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedTGM1
Sources retrieved27 papers
Response timeβ€”
πŸ“„ Sources
27β–Ό
1
Anti-Wrinkling and Anti-Melanogenic Effect of
PMID: 30818884
Int J Mol Sci Β· 2019
1.00
2
Meta-Analysis of Mutations in
PMID: 33435499
Genes (Basel) Β· 2021
0.90
3
The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds.
PMID: 34851365
JAMA Dermatol Β· 2022
0.80
4
TGM1 as a novel signature gene in psoriasis identified by integrative bioinformatics and experimental validation.
PMID: 41268597
Mol Med Rep Β· 2026
0.70
5
Structure and organization of the human transglutaminase 1 gene.
PMID: 1348508
J Biol Chem Β· 1992
0.68