GGTLC2

Summary

GGTLC2 (gamma-glutamyltransferase light chain 2, HGNC:18596) is a protein-coding gene on chromosome 22q11.22, encoding Glutathione hydrolase light chain 2 (Q14390). It is a common-essential gene (DepMap: required in 96.0% of cancer cell lines).

This gene encodes a protein related to enzymes that cleaves gamma-glutamyl peptide bonds in glutathione and other peptides. Unlike similar proteins, the encoded protein contains only the light chain portion and may not have catalytic activity. Alternative splicing results in multiple transcript variants. There are several related family members and related pseudogene for this gene situated in the same region of chromosome 22.

Source: NCBI Gene 91227 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 64 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 96.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_199127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18596
Approved symbol	GGTLC2
Name	gamma-glutamyltransferase light chain 2
Location	22q11.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100121
Ensembl biotype	protein_coding
OMIM	612339
Entrez	91227

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000417145, ENST00000448514, ENST00000480559, ENST00000651213, ENST00000652219, ENST00000652249, ENST00000652467

RefSeq mRNA: 4 — MANE Select: NM_199127 NM_001282879, NM_001391910, NM_001391911, NM_199127

CCDS: CCDS13802, CCDS93129

Canonical transcript exons

ENST00000448514 — 6 exons

Exon	Start	End
ENSE00001660620	22647141	22647290
ENSE00001670430	22646983	22647038
ENSE00001719064	22647595	22647898
ENSE00003672221	22646754	22646881
ENSE00003745995	22646312	22646521
ENSE00003841444	22644614	22644708

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 84.46.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	84.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.41	gold quality
testis	UBERON:0000473	82.32	gold quality
left testis	UBERON:0004533	81.83	gold quality
blood	UBERON:0000178	79.09	gold quality
granulocyte	CL:0000094	72.48	gold quality
monocyte	CL:0000576	70.58	gold quality
leukocyte	CL:0000738	70.35	gold quality
right lung	UBERON:0002167	69.76	gold quality
spleen	UBERON:0002106	68.65	gold quality
upper lobe of left lung	UBERON:0008952	63.73	gold quality
right coronary artery	UBERON:0001625	61.92	gold quality
right lobe of thyroid gland	UBERON:0001119	61.70	gold quality
placenta	UBERON:0001987	60.65	gold quality
lung	UBERON:0002048	60.28	gold quality
colonic epithelium	UBERON:0000397	59.21	gold quality
bone marrow cell	CL:0002092	58.64	gold quality
stromal cell of endometrium	CL:0002255	58.24	gold quality
left lobe of thyroid gland	UBERON:0001120	57.79	gold quality
thyroid gland	UBERON:0002046	57.60	gold quality
adult mammalian kidney	UBERON:0000082	57.29	gold quality
kidney	UBERON:0002113	56.90	gold quality
sural nerve	UBERON:0015488	55.74	silver quality
metanephros cortex	UBERON:0010533	55.47	gold quality
vermiform appendix	UBERON:0001154	55.02	gold quality
cortex of kidney	UBERON:0001225	55.01	gold quality
mucosa of stomach	UBERON:0001199	53.18	gold quality
liver	UBERON:0002107	53.05	gold quality
bone marrow	UBERON:0002371	53.03	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting GGTLC2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4308	97.56	67.13	1385

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.0% of screened cell lines, common-essential.

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), GGT7 (ENSG00000131067), GGTLC1 (ENSG00000149435), GGT6 (ENSG00000167741), GGTLC3 (ENSG00000274252)

Protein

Protein identifiers

Glutathione hydrolase light chain 2 — Q14390 (reviewed: Q14390)

Alternative names: Gamma-glutamyltransferase light chain 2, Gamma-glutamyltransferase-like protein 4

All UniProt accessions (6): Q14390, A0A494C0N1, A0A494C112, A0A494C1E1, A0A494C1J8, A0A494C1L7

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Placenta and sigmoid tissues.

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 (4): NP_001269808, NP_001378839, NP_001378840, NP_954578* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000101	GGT_peptidase	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR043137	GGT_ssub_C	Homologous_superfamily
IPR043138	GGT_lsub	Homologous_superfamily
IPR055262	GGT_CS	Conserved_site

Pfam: PF01019

UniProt features (9 total): binding site 3, sequence variant 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14390-F1	90.14	0.73

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 (3): 55; 76; 107–108

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (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 (1): extracellular exosome (GO:0070062)

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
extracellular vesicle	1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGTLC2	GGT6	Q6P531	848
GGTLC2	POM121L1P	Q3SYA9	695
GGTLC2	ZNF280A	P59817	621
GGTLC2	ZNF280B	Q86YH2	600
GGTLC2	A0A1W2PQ80	A0A1W2PQ80	520
GGTLC2	IGKV2D-29	A0A075B6S2	495
GGTLC2	POM121	Q96HA1	477
GGTLC2	IGKV2-40	A0A087WW87	462
GGTLC2	OR4A5	Q8NH83	448
GGTLC2	OR4C12	Q96R67	432
GGTLC2	PRAME	P78395	395
GGTLC2	EVA1B	Q9NVM1	378
GGTLC2	RSPH14	Q9UHP6	373
GGTLC2	GPCPD1	Q9NPB8	350
GGTLC2	SLC20A1	Q8WUM9	349
GGTLC2	SLC20A2	Q08357	349

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TLX3	GGTLC2	psi-mi:“MI:0915”(physical association)	0.560
TLX3	GGTLC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): TLX3 (Two-hybrid), GGTLC2 (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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625624	GRCh37/hg19 22q11.22(chr22:22255329-23321856)	Pathogenic

SpliceAI

952 predictions. Top by Δscore:

Variant	Effect	Δscore
22:22644643:GCCAG:G	donor_gain	1.0000
22:22644644:CCAGG:C	donor_loss	1.0000
22:22644645:CAGG:C	donor_loss	1.0000
22:22644646:AG:A	donor_loss	1.0000
22:22644647:GGTA:G	donor_loss	1.0000
22:22644648:G:T	donor_loss	1.0000
22:22644649:T:G	donor_loss	1.0000
22:22646481:G:GT	donor_gain	1.0000
22:22646522:G:GG	donor_gain	1.0000
22:22646877:GCCAG:G	donor_gain	1.0000
22:22646879:CAGG:C	donor_loss	1.0000
22:22646880:AGGT:A	donor_loss	1.0000
22:22647119:T:TA	acceptor_gain	1.0000
22:22647274:A:T	donor_gain	1.0000
22:22647288:CAGGT:C	donor_loss	1.0000
22:22647290:GGTGG:G	donor_loss	1.0000
22:22647291:G:GC	donor_loss	1.0000
22:22646485:G:GT	donor_gain	0.9900
22:22646487:A:AG	donor_gain	0.9900
22:22646488:G:GG	donor_gain	0.9900
22:22646517:CTCTA:C	donor_gain	0.9900
22:22646520:TAGT:T	donor_loss	0.9900
22:22646521:AGT:A	donor_loss	0.9900
22:22646523:T:G	donor_loss	0.9900
22:22646882:GT:G	donor_loss	0.9900
22:22646883:T:G	donor_loss	0.9900
22:22646972:ATC:A	acceptor_gain	0.9900
22:22646972:ATCG:A	acceptor_gain	0.9900
22:22646974:C:A	acceptor_gain	0.9900
22:22646975:G:A	acceptor_gain	0.9900

AlphaMissense

1431 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:22646815:T:C	F80L	0.983
22:22646817:C:A	F80L	0.983
22:22646817:C:G	F80L	0.983
22:22646842:T:C	F89L	0.967
22:22646844:T:A	F89L	0.967
22:22646844:T:G	F89L	0.967
22:22646505:A:C	S54R	0.966
22:22646507:C:A	S54R	0.966
22:22646507:C:G	S54R	0.966
22:22646814:C:A	D79E	0.957
22:22646814:C:G	D79E	0.957
22:22646818:A:C	S81R	0.948
22:22646820:C:A	S81R	0.948
22:22646820:C:G	S81R	0.948
22:22647714:G:C	R210S	0.940
22:22647714:G:T	R210S	0.940
22:22647706:G:C	D208H	0.938
22:22647713:G:T	R210M	0.936
22:22646509:C:T	T55I	0.930
22:22647717:A:C	K211N	0.930
22:22647717:A:T	K211N	0.930
22:22647708:C:A	D208E	0.927
22:22647708:C:G	D208E	0.927
22:22646755:T:C	F60L	0.925
22:22646757:T:A	F60L	0.925
22:22646757:T:G	F60L	0.925
22:22647698:C:A	A205D	0.921
22:22647707:A:T	D208V	0.921
22:22646430:T:C	F29L	0.919
22:22646432:C:A	F29L	0.919

dbSNP variants (sampled 300 via entrez): RS1001823903 (22:22645103 A>G,T), RS1002101936 (22:22642821 C>G,T), RS1002273401 (22:22648152 T>A), RS1002772637 (22:22646148 G>A), RS1005513690 (22:22643581 T>A), RS1005564784 (22:22643997 A>C,G), RS1006118421 (22:22647826 C>A,T), RS1006587713 (22:22648063 G>A,T), RS1006618082 (22:22645731 T>C,G), RS1006973548 (22:22645452 T>C), RS1008907803 (22:22646691 G>A,C,T), RS1009460233 (22:22643485 T>C), RS1009810638 (22:22648278 G>A), RS1010327725 (22:22647408 C>T), RS1013042842 (22:22646199 G>A,T)

Disease associations

OMIM: gene MIM:612339 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001277_20	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-109
GCST010577_19	Crohn’s disease	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Pesticides	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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