TGM3

transglutaminase 3, the group of Transglutaminases

Basic information

Region (hg38): 20:2296001-2341079

Links

ENSG00000125780

∙ NCBI:7053 ∙ OMIM:600238 ∙ HGNC:11779 ∙ Uniprot:Q08188 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

uncombable hair syndrome (Supportive), mode of inheritance: AR
uncombable hair syndrome 2 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Uncombable hair syndrome 2	AR	General	The clinical relevance of the condition is unclear	Dermatologic	27866708

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TGM3 gene.

not_specified (110 variants)
TGM3-related_disorder (21 variants)
not_provided (9 variants)
Uncombable_hair_syndrome_2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGM3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003245.4. 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	5 clinvar	15
missense			105 clinvar	8 clinvar	4 clinvar	117
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	105	18	9

Highest pathogenic variant AF is 0.000034338773

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGM3	protein_coding	protein_coding	ENST00000381458	13	45078

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000297	0.999	125695	0	52	125747	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.411	447	423	1.06	0.0000267	4568
Missense in Polyphen		159	163.06	0.97512		1815
Synonymous	-1.18	198	178	1.11	0.0000127	1363
Loss of Function	2.98	15	33.7	0.446	0.00000178	342

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000293	0.000290
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross- linking structural proteins to hardening the inner root sheath. {ECO:0000250}.;
Disease: DISEASE: Uncombable hair syndrome 2 (UHS2) [MIM:617251]: A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age. {ECO:0000269|PubMed:27866708}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.219

Intolerance Scores

loftool: 0.320
rvis_EVS: -0.21
rvis_percentile_EVS: 37.76

Haploinsufficiency Scores

pHI: 0.360
hipred: N
hipred_score: 0.380
ghis: 0.408

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.538

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tgm3
Phenotype: homeostasis/metabolism phenotype; 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); 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); limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: cellular protein modification process;peptide cross-linking;keratinocyte differentiation;hair follicle morphogenesis;keratinization;cell envelope organization;protein tetramerization
Cellular component: cytoplasm;extrinsic component of cytoplasmic side of plasma membrane;extracellular exosome
Molecular function: protein-glutamine gamma-glutamyltransferase activity;catalytic activity;calcium ion binding;transferase activity, transferring acyl groups