GGH

gamma-glutamyl hydrolase, the group of Glutamine amidotransferase class 1 domain containing

Basic information

Region (hg38): 8:63014880-63039407

Links

ENSG00000137563 ∙ NCBI:8836 ∙ OMIM:601509 ∙ HGNC:4248 ∙ Uniprot:Q92820 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (14 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GGH 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			13	1	1	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	1	2

Variants in GGH

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

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

Position	Type	Phenotype	Significance	ClinVar
8-63015366-A-G		not specified	Uncertain significance (Oct 12, 2022)
8-63015406-C-T		not specified	Uncertain significance (Dec 09, 2023)
8-63017495-T-C		not specified	Uncertain significance (Dec 20, 2023)
8-63017519-T-G		not specified	Uncertain significance (Jan 23, 2024)
8-63017549-T-C		not specified	Uncertain significance (Dec 18, 2023)
8-63017624-T-C		not specified	Uncertain significance (Dec 19, 2022)
8-63017628-A-G		not specified	Uncertain significance (Nov 07, 2022)
8-63023913-T-C		not specified	Uncertain significance (Jun 22, 2022)
8-63023916-T-C		not specified	Uncertain significance (Nov 29, 2021)
8-63024099-T-C		not specified	Uncertain significance (Jul 09, 2021)
8-63024151-T-C		not specified	Likely benign (Oct 05, 2022)
8-63026176-G-A		not specified	Uncertain significance (Jun 02, 2023)
8-63026190-A-G		not specified	Uncertain significance (Feb 16, 2023)
8-63026193-G-A		not specified	Uncertain significance (May 28, 2023)
8-63027237-G-C		not specified	Uncertain significance (Jan 26, 2023)
8-63030174-T-C			Benign (Jul 17, 2018)
8-63035639-A-AC			Likely benign (Dec 20, 2023)
8-63035701-T-C		not specified	Uncertain significance (Aug 12, 2021)
8-63035706-C-T			Benign (Jun 20, 2018)
8-63038692-G-T		not specified	Uncertain significance (Oct 03, 2022)
8-63038752-C-T		not specified	Uncertain significance (Apr 10, 2023)
8-63038756-C-T		not specified	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GGH	protein_coding	protein_coding	ENST00000260118	9	24093

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.581	0.418	125716	0	18	125734	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.451	144	160	0.900	0.00000778	2067
Missense in Polyphen		40	54.555	0.73321		727
Synonymous	-0.289	62	59.2	1.05	0.00000300	568
Loss of Function	2.96	3	15.7	0.192	6.57e-7	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000273	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000549	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000361	0.0000352
Middle Eastern	0.0000549	0.0000544
South Asian	0.000213	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha- glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.
• Pathway: Fluoropyrimidine Pathway, Pharmacodynamics;Folate biosynthesis - Homo sapiens (human);Methotrexate Pathway (Cancer Cell), Pharmacodynamics;Folate malabsorption, hereditary;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;Fluoropyrimidine Activity;Neutrophil degranulation;glutathione-mediated detoxification;Innate Immune System;Immune System;glutamate removal from folates (Consensus)

Recessive Scores

• pRec: 0.237

Intolerance Scores

• loftool: 0.592
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.225
• hipred: N
• hipred_score: 0.355
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ggh

Gene ontology

• Biological process: proteolysis;response to zinc ion;response to insulin;neutrophil degranulation;response to ethanol;tetrahydrofolylpolyglutamate metabolic process
• Cellular component: extracellular region;extracellular space;nucleus;vacuole;cytosol;azurophil granule lumen;specific granule lumen;melanosome;extracellular exosome;tertiary granule lumen
• Molecular function: exopeptidase activity;omega peptidase activity;gamma-glutamyl-peptidase activity