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Protein / target

Gamma-glutamyl hydrolase

Encoded byGGHQ92820Homo sapiensSwiss-Prot
UniProt: Q92820Ensembl: ENSG00000137563HGNC: HGNC:4248NCBI Gene: 8836
Small-molecule tractable
Druggability
Druggable Family
1
Research papers

Protein at a glance

Biological role

Gamma-glutamyl-peptidase

Strongest disease association

Alcohol drinking

Via encoding gene GGH · Genetic evidence · score 0.10

Research activity

Emerging research

1 papers · latest 2016

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates.

View complete UniProt function annotation

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 (PubMed:11005824, PubMed:8816764). May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates

Subcellular location

Secreted, extracellular spaceLysosomeMelanosome
Domains and Gene Ontology detail (15)

Domains & features

Gamma-glutamyl hydrolase

Gene Ontology

  • Cazurophil granule lumen
  • Cendoplasmic reticulum
  • Cextracellular exosome
  • Cextracellular region
  • Cextracellular space
  • Cmelanosome
  • Cnucleus
  • Cspecific granule lumen
  • Ctertiary granule lumen
  • Cvacuole
  • Fexopeptidase activity
  • Fgamma-glutamyl-peptidase activity

318 aa · 36 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

ProteolysisGO
View supporting evidence

Proteolysis

  • ·exopeptidase activity
  • ·gamma-glutamyl-peptidase activity
  • ·omega peptidase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GGH

Gene-level evidence surfaced through the gene GGH that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neoplasms
0.11Preliminary

Literature evidence dominant · Open Targets 0.09 · no direct causal or clinical evidence

Carcinoma, Non-Small-Cell Lung
0.11Preliminary

Literature evidence dominant · Open Targets 0.07 · no direct causal or clinical evidence

Alcohol drinking
0.10Preliminary

Genetic evidence dominant · Open Targets 0.06

Urolithiasis
0.10Preliminary

Genetic evidence dominant · Open Targets 0.06

View evidence synthesis (4)
NeoplasmsPreliminary
0.11
agreement 0.00–0.39
Literature100%

Open Targets aggregate 0.09 · 1 independent evidence family · no direct causal or clinical evidence

Carcinoma, Non-Small-Cell LungPreliminary
0.11
agreement 0.00–0.30
Literature75%RNA expression26%

Open Targets aggregate 0.07 · 2 independent evidence families · no direct causal or clinical evidence

Alcohol drinkingPreliminary
0.10
agreement 0.00–0.24
Genetic97%Literature3%

Open Targets aggregate 0.06 · 2 independent evidence families

UrolithiasisPreliminary
0.10
agreement 0.00–0.22
Genetic100%

Open Targets aggregate 0.06 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neoplasms0.09
Carcinoma, Non-Small-Cell Lung0.07
Alcohol drinking0.06
Urolithiasis0.06

Tractability

Small molecules — Emerging

Feasibility evidence (druggable family) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

drug toxicityClinPGxaccumulation of active methotrexate metabolitesClinPGxbone marrow toxicityClinPGxthrombocytopeniaClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2016

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Preventing and Managing Toxicities of High-Dose Methotrexate.538 cites

Howard SC · The oncologist · 2016

Recent

Preventing and Managing Toxicities of High-Dose Methotrexate.

Howard SC · The oncologist · 2016

Europe PMC papers linked directly to this protein.