GGT1

gamma-glutamyltransferase 1, the group of CD molecules|Gamma-glutamyltransferases

Basic information

Region (hg38): 22:24594810-24629005

Previous symbols: [ "GGT" ]

Links

ENSG00000100031 ∙ NCBI:2678 ∙ OMIM:612346 ∙ HGNC:4250 ∙ Uniprot:P19440 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• gamma-glutamyl transpeptidase deficiency (Limited), mode of inheritance: AR
• gamma-glutamyl transpeptidase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glutathionuria	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	Biochemical; Neurologic	29483667

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GGT1 gene.

• not provided (43 variants)
• Inborn genetic diseases (25 variants)
• gamma-Glutamyltransferase deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GGT1 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				7	5	12
missense			23	6	2	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					25	25
Total	0	0	23	13	32

Variants in GGT1

This is a list of pathogenic ClinVar variants found in the GGT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-24610949-T-C			Benign (Jun 15, 2019)
22-24611096-A-T		not specified	Likely benign (Nov 09, 2022)
22-24611165-A-G			Benign (Jun 15, 2019)
22-24611167-C-T		not specified	Uncertain significance (Jul 27, 2021)
22-24611208-G-A		gamma-Glutamyltransferase deficiency	Uncertain significance (Jun 09, 2020)
22-24611214-G-A		not specified	Uncertain significance (Jun 16, 2023)
22-24611235-A-G			Likely benign (Nov 01, 2023)
22-24611384-A-G			Benign (Jun 15, 2019)
22-24614614-CA-C			Benign (Aug 07, 2019)
22-24614779-T-C			Benign (Jun 14, 2019)
22-24614796-G-C		not specified	Uncertain significance (Nov 30, 2021)
22-24614802-C-T		not specified	Uncertain significance (Nov 08, 2022)
22-24614918-G-A			Benign (Jun 15, 2019)
22-24614974-G-A			Benign (Jun 21, 2019)
22-24614976-T-C			Benign (Jun 15, 2019)
22-24615000-G-C			Benign (Jun 15, 2019)
22-24615070-G-T		not specified	Uncertain significance (Feb 14, 2023)
22-24615142-A-C			Benign (Jun 28, 2019)
22-24615302-T-C			Benign (Jun 14, 2019)
22-24615353-T-C			Benign (Jun 14, 2019)
22-24615365-A-G			Benign (Jun 14, 2019)
22-24620074-A-G			Benign (Jun 28, 2019)
22-24620239-A-G			Benign (Jun 14, 2019)
22-24620240-T-C			Benign (Jun 14, 2019)
22-24620344-G-A			Benign (Jun 15, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GGT1	protein_coding	protein_coding	ENST00000400382	12	45255

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000753	0.996	125515	2	74	125591	0.000303

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.857	310	355	0.872	0.0000234	3609
Missense in Polyphen		71	101.12	0.70211		1054
Synonymous	0.0906	162	163	0.991	0.0000122	1187
Loss of Function	2.55	11	24.7	0.446	0.00000134	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000245	0.000236
Ashkenazi Jewish	0.00	0.00
East Asian	0.000121	0.000109
Finnish	0.00130	0.00125
European (Non-Finnish)	0.000270	0.000264
Middle Eastern	0.000121	0.000109
South Asian	0.000261	0.000229
Other	0.000498	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive. {ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}.
• Disease: DISEASE: Glutathionuria (GLUTH) [MIM:231950]: A very rare, autosomal recessive metabolic disorder characterized by the presence of glutathione in the urine, due to generalized gamma- glutamyl transpeptidase deficiency. Most patients manifest mild to moderate mental retardation, and behavioral disturbance. Seizures, tremor, marfanoid features and strabismus are observed in some patients. {ECO:0000269|PubMed:29483667}. Note=The disease is caused by mutations affecting the gene represented in this entry. A large homozygous deletion that removes several exons of all isoforms of GGT1 has been found in one family affected by glutathionuria. {ECO:0000269|PubMed:29483667}.
• Pathway: Glutathione metabolism - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Taurine and hypotaurine metabolism - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Leukotriene modifiers pathway, Pharmacodynamics;Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Selenoamino Acid Metabolism;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Glutathione metabolism;Selenium Micronutrient Network;Eicosanoid Synthesis;Nuclear Receptors Meta-Pathway;NRF2 pathway;Glutathione conjugation;Metabolism of lipids;Phase II - Conjugation of compounds;Prostaglandin Leukotriene metabolism;Synthesis of Leukotrienes (LT) and Eoxins (EX);Arachidonic acid metabolism;Biological oxidations;Metabolism;Fatty acid metabolism;Glutathione synthesis and recycling;Aflatoxin activation and detoxification (Consensus)

Recessive Scores

• pRec: 0.828

Intolerance Scores

• loftool: 0.855
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.380
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.124

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ggt1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region 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); homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; hematopoietic system 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); reproductive system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: regulation of immune system process;translation;proteolysis;cellular amino acid metabolic process;glutamate metabolic process;fatty acid metabolic process;leukotriene metabolic process;glutathione metabolic process;glutathione biosynthetic process;glutathione catabolic process;xenobiotic metabolic process;spermatogenesis;cysteine biosynthetic process;peptide modification;zymogen activation;response to estradiol;response to lipopolysaccharide;response to tumor necrosis factor;regulation of inflammatory response;leukotriene D4 biosynthetic process
• Cellular component: extracellular space;plasma membrane;integral component of membrane;extracellular exosome
• Molecular function: peptidyltransferase activity;leukotriene-C(4) hydrolase;protein binding;glutathione hydrolase activity;hypoglycin A gamma-glutamyl transpeptidase activity;leukotriene C4 gamma-glutamyl transferase activity