GGTLC1

Summary

GGTLC1 (gamma-glutamyltransferase light chain 1, HGNC:16437) is a protein-coding gene on chromosome 20p11.21, encoding Glutathione hydrolase light chain 1 (Q9BX51).

This gene encodes a member of the gamma-glutamyl transpeptidase (GGT) family, which are important in the metabolism of glutathione. The most ubiquitously expressed human GGT gene, GGT1, encodes a single transmembrane polypeptide that is post-translationally processed to form a heavy and a light chain. In contrast, the product of this gene only contains homology to the light chain region, and lacks a transmembrane domain. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 92086 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_178311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16437
Approved symbol	GGTLC1
Name	gamma-glutamyltransferase light chain 1
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ831C21.2, dJ831C21.1
Ensembl gene	ENSG00000149435
Ensembl biotype	protein_coding
OMIM	612338
Entrez	92086

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000278765, ENST00000286890, ENST00000335694, ENST00000969294

RefSeq mRNA: 2 — MANE Select: NM_178311 NM_178311, NM_178312

CCDS: CCDS13163

Canonical transcript exons

ENST00000335694 — 6 exons

Exon	Start	End
ENSE00001361149	23988609	23988779
ENSE00001626580	23985053	23985362
ENSE00001657900	23985862	23985974
ENSE00001668150	23986076	23986203
ENSE00001789079	23986436	23986645
ENSE00001789545	23985667	23985780

Expression profiles

Bgee: expression breadth broad, 40 present calls, max score 94.11.

Top tissues by expression

101 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	94.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.37	silver quality
upper lobe of left lung	UBERON:0008952	89.77	gold quality
lung	UBERON:0002048	84.30	gold quality
right testis	UBERON:0004534	80.37	gold quality
left testis	UBERON:0004533	79.50	gold quality
testis	UBERON:0000473	79.35	gold quality
left lobe of thyroid gland	UBERON:0001120	63.47	gold quality
right lobe of thyroid gland	UBERON:0001119	62.54	gold quality
thyroid gland	UBERON:0002046	62.06	gold quality
colonic epithelium	UBERON:0000397	45.93	gold quality
body of pancreas	UBERON:0001150	45.04	gold quality
metanephros cortex	UBERON:0010533	44.67	gold quality
bone marrow cell	CL:0002092	42.56	gold quality
adult mammalian kidney	UBERON:0000082	41.76	gold quality
duodenum	UBERON:0002114	41.60	gold quality
pancreas	UBERON:0001264	40.88	gold quality
kidney	UBERON:0002113	39.88	gold quality
muscle tissue	UBERON:0002385	38.96	gold quality
mucosa of transverse colon	UBERON:0004991	38.03	silver quality
lymph node	UBERON:0000029	37.75	silver quality
granulocyte	CL:0000094	37.41	gold quality
cortex of kidney	UBERON:0001225	36.89	gold quality
sural nerve	UBERON:0015488	36.66	gold quality
liver	UBERON:0002107	36.57	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	36.22	gold quality
tonsil	UBERON:0002372	36.18	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	ggt1b	ENSDARG00000018342
danio_rerio	ggt1a	ENSDARG00000023526
danio_rerio	ggt1l2.1	ENSDARG00000075055
danio_rerio	si:ch73-236c18.3	ENSDARG00000075541
danio_rerio	ggt1l2.2	ENSDARG00000087054
danio_rerio	si:ch73-59p9.2	ENSDARG00000091254
danio_rerio	si:dkey-222h21.12	ENSDARG00000092350
danio_rerio		ENSDARG00000098576
mus_musculus	Ggt1	ENSMUSG00000006345
rattus_norvegicus	Ggt1	ENSRNOG00000047697
drosophila_melanogaster	CG17636	FBGN0025837
drosophila_melanogaster	Ggt-1	FBGN0030932

Paralogs (6): GGT5 (ENSG00000099998), GGT1 (ENSG00000100031), GGTLC2 (ENSG00000100121), GGT7 (ENSG00000131067), GGT6 (ENSG00000167741), GGTLC3 (ENSG00000274252)

Protein

Protein identifiers

Glutathione hydrolase light chain 1 — Q9BX51 (reviewed: Q9BX51)

Alternative names: Gamma-glutamyltransferase light chain 1, Gamma-glutamyltransferase-like activity 4, Gamma-glutamyltransferase-like protein 6

All UniProt accessions (1): Q9BX51

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. Corresponds to the light chain of other gamma-glutamyltransferase family members. Has no catalytic activity.

Similarity. Belongs to the gamma-glutamyltransferase family.

RefSeq proteins (2): NP_842563, NP_842564 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000101	GGT_peptidase	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR043137	GGT_ssub_C	Homologous_superfamily
IPR055262	GGT_CS	Conserved_site

Pfam: PF01019

UniProt features (6 total): binding site 4, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BX51-F1	93.42	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 37 (nucleophile)

Ligand- & substrate-binding residues (4): 55; 76; 107–108; 129–130

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GOBP_LEUKOTRIENE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_GLUTATHIONE_METABOLIC_PROCESS, GOBP_FATTY_ACID_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_FATTY_ACID_DERIVATIVE_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_METABOLIC_PROCESS

GO Biological Process (2): glutathione catabolic process (GO:0006751), leukotriene D4 biosynthetic process (GO:1901750)

GO Molecular Function (2): glutathione gamma-glutamate hydrolase (GO:0036374), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glutathione metabolic process	1
modified amino acid catabolic process	1
sulfur compound catabolic process	1
leukotriene biosynthetic process	1
sulfur compound biosynthetic process	1
fatty acid derivative biosynthetic process	1
omega peptidase activity	1
threonine-type peptidase activity	1
binding	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGTLC1	GGT6	Q6P531	844
GGTLC1	POM121L1P	Q3SYA9	571
GGTLC1	ACTL10	Q5JWF8	401
GGTLC1	AKR1B10	O60218	372
GGTLC1	CA11	O75493	356
GGTLC1	USP1	O94782	349
GGTLC1	FTL	P02792	348
GGTLC1	GCLC	P48506	343
GGTLC1	TDRD10	Q5VZ19	336
GGTLC1	RCE1	Q9Y256	334
GGTLC1	ATAD3C	Q5T2N8	324
GGTLC1	POM121	Q96HA1	318
GGTLC1	ABHD1	Q96SE0	308
GGTLC1	TMEM130	Q8N3G9	304
GGTLC1	GGT7	Q9UJ14	301

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GGTLC1	GSTA1	psi-mi:“MI:0915”(physical association)	0.590
GGTLC1	VPS41	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): GSTA1 (Affinity Capture-MS), GSTA1 (Affinity Capture-MS), RICTOR (Affinity Capture-MS), VPS41 (Affinity Capture-MS), GGTLC1 (Negative Genetic), GGTLC1 (Negative Genetic), GGTLC1 (Negative Genetic)

ESM2 similar proteins: A6NGU5, B5MD39, B6EWW8, D4B387, F8S0Z7, O35409, O77564, P07314, P07686, P0DPU3, P0DPU6, P15693, P17439, P19111, P19440, P20735, P21588, P24822, P24823, P36268, P36269, P49614, P58242, P70627, Q04609, Q05927, Q0V8L2, Q14390, Q29548, Q2KHZ8, Q501L1, Q5RFI5, Q5RFU0, Q5TYS5, Q5XIG6, Q60928, Q680I5, Q68FH4, Q6DH69, Q6GMR7

Diamond homologs: A6NGU5, B5MD39, B8NM71, D4B387, O14194, P07314, P0DPU3, P0DPU6, P18956, P19440, P20735, P36267, P36268, P36269, P54422, P63186, Q05902, Q0V8L2, Q14390, Q60928, Q680I5, Q8VYW6, Q99JP7, Q99MZ4, Q9BX51, Q9CAR5, Q9I406, Q9M0G0, Q9QWE9, Q9UJ14, Q9US04, Q9Z2A9, A6T9C8, P15557, Q05053, Q51693, Q6P531, Q6IE08, O05218, A7YWM1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

45 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

523 predictions. Top by Δscore:

Variant	Effect	Δscore
20:23985359:CTTC:C	acceptor_gain	1.0000
20:23985661:GCCCA:G	donor_loss	1.0000
20:23985662:CCCA:C	donor_loss	1.0000
20:23985663:CCA:C	donor_loss	1.0000
20:23985664:CACC:C	donor_loss	1.0000
20:23985665:A:C	donor_loss	1.0000
20:23985666:C:A	donor_loss	1.0000
20:23985683:T:A	donor_gain	1.0000
20:23985777:TGGC:T	acceptor_gain	1.0000
20:23985781:C:CA	acceptor_loss	1.0000
20:23985781:C:CC	acceptor_gain	1.0000
20:23985782:T:G	acceptor_loss	1.0000
20:23985857:CATA:C	donor_loss	1.0000
20:23985858:ATAC:A	donor_loss	1.0000
20:23985859:TACC:T	donor_loss	1.0000
20:23985860:A:AC	donor_gain	1.0000
20:23985861:C:CC	donor_gain	1.0000
20:23985861:CCA:C	donor_gain	1.0000
20:23985970:CTTCC:C	acceptor_gain	1.0000
20:23985972:TCC:T	acceptor_gain	1.0000
20:23985973:CC:C	acceptor_gain	1.0000
20:23985973:CCC:C	acceptor_gain	1.0000
20:23985974:CC:C	acceptor_gain	1.0000
20:23985975:C:A	acceptor_loss	1.0000
20:23985975:C:CC	acceptor_gain	1.0000
20:23985975:C:T	acceptor_gain	1.0000
20:23985976:T:G	acceptor_loss	1.0000
20:23985979:G:T	acceptor_gain	1.0000
20:23985981:CCAA:C	acceptor_gain	1.0000
20:23985982:C:CT	acceptor_gain	1.0000

AlphaMissense

1476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:23986140:G:C	F80L	0.984
20:23986140:G:T	F80L	0.984
20:23986142:A:G	F80L	0.984
20:23986113:A:C	F89L	0.965
20:23986113:A:T	F89L	0.965
20:23986115:A:G	F89L	0.965
20:23986450:G:C	S54R	0.965
20:23986450:G:T	S54R	0.965
20:23986452:T:G	S54R	0.965
20:23986143:G:C	D79E	0.950
20:23986143:G:T	D79E	0.950
20:23986448:G:A	T55I	0.945
20:23986441:G:C	N57K	0.943
20:23986441:G:T	N57K	0.943
20:23986158:A:C	N74K	0.937
20:23986158:A:T	N74K	0.937
20:23986137:G:C	S81R	0.925
20:23986137:G:T	S81R	0.925
20:23986139:T:G	S81R	0.925
20:23985243:C:A	R217S	0.924
20:23985243:C:G	R217S	0.924
20:23986089:A:C	N97K	0.923
20:23986089:A:T	N97K	0.923
20:23985244:C:A	R217M	0.921
20:23986159:T:A	N74I	0.916
20:23985881:A:G	I133T	0.914
20:23986155:A:C	N75K	0.911
20:23986155:A:T	N75K	0.911
20:23986460:G:T	S51Y	0.911
20:23986141:A:G	F80S	0.910

dbSNP variants (sampled 300 via entrez): RS1000132813 (20:23984607 C>A,T), RS1000467372 (20:23988655 A>T), RS1000813768 (20:23988900 C>G,T), RS1001420836 (20:23987855 C>T), RS1001871991 (20:23987631 G>A), RS1002834450 (20:23986801 G>A), RS1002957677 (20:23989859 T>C), RS1003409079 (20:23990046 C>T), RS1003889999 (20:23985708 G>A,T), RS1004414180 (20:23986842 G>C), RS1004982679 (20:23990107 C>T), RS1005910615 (20:23989197 G>A,C), RS1006429299 (20:23984993 C>G), RS1006989412 (20:23988461 T>C), RS1007921238 (20:23987150 A>G,T)

Disease associations

OMIM: gene MIM:612338 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000824_9	Erectile dysfunction and prostate cancer treatment	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases expression	2
Valproic Acid	increases methylation, decreases expression, increases expression	2
benzo(e)pyrene	increases methylation	1
shogaol	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
Testosterone	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.