GGT6

protein-coding

gamma-glutamyltransferase 6, the group of Gamma-glutamyltransferases

Gene summary

GGT6 belongs to the gamma-glutamyltransferase (GGT; EC 2.3.2.2) gene family. GGT is a membrane-bound extracellular enzyme that cleaves gamma-glutamyl peptide bonds in glutathione and other peptides and transfers the gamma-glutamyl moiety to acceptors. GGT is also key to glutathione homeostasis because it provides substrates for glutathione synthesis (Heisterkamp et al., 2008 [PubMed 18357469]).[supplied by OMIM, Oct 2008]

MANE transcript

NM_001288702.2

Inheritance

—

ClinVar variants

U:88B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr17:4,556,927-4,560,818

External References & Databases

Ensembl (ENSG00000167741)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GGT6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001288702.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			88 clinvar	11 clinvar	1 clinvar	100
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	88	11	2	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001288702.2	RefSeq	NP_001275631.1	4	MANE Select
ENST00000381550.8	Ensembl	ENSP00000370962.3	4	MANE Select
NM_001122890.3	RefSeq	NP_001116362.1	4	Standard
NM_001288703.2	RefSeq	NP_001275632.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glutathione metabolism - Homo sapiens (human)
Taurine and hypotaurine metabolism - Homo sapiens (human)
Gamma-glutamyl-transpeptidase deficiency
5-oxoprolinase deficiency
Gamma-Glutamyltransferase Deficiency

Biological Process

proteolysis
glutathione biosynthetic process
glutathione catabolic process
biological_process
leukotriene D4 biosynthetic process

Molecular Function

molecular_function
glutathione hydrolase activity
hypoglycin A gamma-glutamyl transpeptidase activity
leukotriene C4 gamma-glutamyl transferase activity

Cellular Component

integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000574154
Coding exons: 4
Length: 3892
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125742
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.321	264	279	0.946	0.0000163	3028
Missense (PolyPhen)		67	75.449	0.88802		932
Synonymous	-0.326	139	134	1.04	0.00000834	1183
Loss of Function	0.204	12	12.8	0.939	7.11e-7	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves glutathione conjugates. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.825
RVIS EVS: 0.51
RVIS percentile EVS: 80.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0103

Gene Damage Prediction

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