GSTZ1

glutathione S-transferase zeta 1, the group of Soluble glutathione S-transferases

Basic information

Region (hg38): 14:77320996-77331597

Links

ENSG00000100577 ∙ NCBI:2954 ∙ OMIM:603758 ∙ HGNC:4643 ∙ Uniprot:O43708 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• maleylacetoacetate isomerase deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Maleylacetoacetate isomerase deficiency	AR	General	The clinical relevance of the condition is unclear	Biochemical	27876694

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GSTZ1 gene.

• Maleylacetoacetate isomerase deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSTZ1 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				1		1
missense		1	12	2	3	18
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)	2					2
splice region				1		1
non coding			2		1	3
Total	2	2	14	3	4

Highest pathogenic variant AF is 0.00000658

Variants in GSTZ1

This is a list of pathogenic ClinVar variants found in the GSTZ1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-77321186-C-G		GSTZ1-related disorder	Likely benign (May 06, 2020)
14-77324600-A-G		GSTZ1-related disorder	Likely benign (Sep 20, 2024)
14-77324892-G-A		not specified	Uncertain significance (Dec 22, 2023)
14-77324919-T-C		not specified	Uncertain significance (Mar 29, 2022)
14-77326826-G-A		Maleylacetoacetate isomerase deficiency	Affects (Jul 26, 2017)
14-77326864-G-A		GSTZ1-related disorder	Benign (Jun 13, 2019)
14-77326868-C-T		not specified	Uncertain significance (Dec 28, 2022)
14-77326869-G-A		GSTZ1-related disorder	Likely benign (Sep 23, 2019)
14-77326893-TG-T		Maleylacetoacetate isomerase deficiency	Likely pathogenic (Jun 20, 2023)
14-77326894-G-A		GSTZ1-related disorder	Benign (Sep 17, 2019)
14-77326898-G-T		not specified	Uncertain significance (Nov 15, 2021)
14-77327470-A-G		Maleylacetoacetate isomerase deficiency	Pathogenic (Jul 03, 2018)
14-77327510-G-T		not specified	Uncertain significance (Oct 02, 2023)
14-77327553-G-A		Maleylacetoacetate isomerase deficiency	Pathogenic (Feb 23, 2023)
14-77327915-G-A		not specified	Uncertain significance (Aug 02, 2021)
14-77327940-T-C		GSTZ1-related disorder	Benign (Oct 30, 2023)
14-77327941-G-A		not specified	Uncertain significance (Mar 08, 2024)
14-77327952-C-T		not specified	Uncertain significance (Dec 27, 2023)
14-77327954-C-T		Maleylacetoacetate isomerase deficiency	other (Apr 10, 2018)
14-77327990-G-A		Maleylacetoacetate isomerase deficiency • GSTZ1-related disorder	Likely pathogenic (May 01, 2022)
14-77327994-G-A		not specified	Uncertain significance (Dec 06, 2021)
14-77328014-G-A		not specified	Uncertain significance (Mar 20, 2023)
14-77329180-G-A		not specified	Uncertain significance (Aug 08, 2022)
14-77329782-C-T		Maleylacetoacetate isomerase deficiency	Affects (Jul 26, 2017)
14-77329800-G-A		not specified	Uncertain significance (Jun 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSTZ1	protein_coding	protein_coding	ENST00000216465	9	10714

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.51e-11	0.0623	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0147	126	126	1.00	0.00000684	1391
Missense in Polyphen		28	35.312	0.79293		448
Synonymous	-0.594	54	48.7	1.11	0.00000288	424
Loss of Function	0.0825	16	16.4	0.978	9.33e-7	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000603	0.000597
Ashkenazi Jewish	0.000315	0.000298
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000161	0.000158
Middle Eastern	0.000217	0.000217
South Asian	0.000307	0.000294
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Bifunctional enzyme showing minimal glutathione- conjugating activity with ethacrynic acid and 7-chloro-4- nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with T- butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid. {ECO:0000269|PubMed:10739172}.
• Pathway: Tyrosine metabolism - Homo sapiens (human);Tyrosinemia, transient, of the newborn;Dopamine beta-hydroxylase deficiency;Disulfiram Action Pathway;Phenylalanine and Tyrosine Metabolism;Tyrosine Metabolism;Alkaptonuria;Monoamine oxidase-a deficiency (MAO-A);Hawkinsinuria;Tyrosinemia Type I;Phenylketonuria;Tyrosinemia Type 3 (TYRO3);Tyrosinemia Type 2 (or Richner-Hanhart syndrome);Metapathway biotransformation Phase I and II;Glutathione conjugation;Phase II - Conjugation of compounds;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;glutathione-mediated detoxification;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Androgen and estrogen biosynthesis and metabolism;Leukotriene metabolism;Phenylalanine and tyrosine catabolism;Biological oxidations;Metabolism;tyrosine degradation;Prostaglandin formation from arachidonate;Tryptophan metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Xenobiotics metabolism;Tyrosine metabolism;Arachidonic acid metabolism (Consensus)

Recessive Scores

• pRec: 0.305

Intolerance Scores

• loftool: 0.929
• rvis_EVS: 0.95
• rvis_percentile_EVS: 90.01

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.251
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.269

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gstz1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); liver/biliary system phenotype; renal/urinary system phenotype; immune system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: L-phenylalanine catabolic process;tyrosine catabolic process;glutathione metabolic process;regulation of acetyl-CoA biosynthetic process from pyruvate;cellular oxidant detoxification;glutathione derivative biosynthetic process
• Cellular component: mitochondrion;mitochondrial matrix;cytosol
• Molecular function: glutathione transferase activity;glutathione peroxidase activity;protein binding;maleylacetoacetate isomerase activity;hydrolase activity, acting on acid halide bonds, in C-halide compounds;identical protein binding;protein homodimerization activity