GGTLC3

Summary

GGTLC3 (gamma-glutamyltransferase light chain family member 3, HGNC:33426) is a protein-coding gene on chromosome 22q11.21, encoding Glutathione hydrolase light chain 3 (B5MD39). Likely to be catalytically inactive.

Gamma-glutamyltransferase-1 (GGT1; MIM 612346) 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. Autocatalytic cleavage of the GGT1 precursor polypeptide produces a heavy chain and a light chain that associate with each other to form the functional enzyme. Light chain-only GGTs, such as GGTLC3, contain a region corresponding to the GGT1 light chain, but they lack the membrane-anchoring heavy chain region (Heisterkamp et al., 2008 [PubMed 18357469]).

Source: NCBI Gene 728226 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001355479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33426
Approved symbol	GGTLC3
Name	gamma-glutamyltransferase light chain family member 3
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000274252
Ensembl biotype	protein_coding
OMIM	612340
Entrez	728226

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000619998, ENST00000962325, ENST00000962326, ENST00000962327

RefSeq mRNA: 1 — MANE Select: NM_001355479 NM_001355479

CCDS: CCDS86996

Canonical transcript exons

ENST00000619998 — 6 exons

Exon	Start	End
ENSE00003716958	18517722	18517931
ENSE00003726674	18516952	18517065
ENSE00003740248	18517362	18517489
ENSE00003745033	18517147	18517259
ENSE00003745456	18516344	18516647
ENSE00003746089	18518063	18518161

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 83.59.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.59	gold quality
right lobe of thyroid gland	UBERON:0001119	79.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.87	silver quality
left lobe of thyroid gland	UBERON:0001120	74.13	gold quality
thyroid gland	UBERON:0002046	73.58	gold quality
adult mammalian kidney	UBERON:0000082	64.82	gold quality
right lung	UBERON:0002167	63.19	gold quality
upper lobe of left lung	UBERON:0008952	62.11	gold quality
metanephros cortex	UBERON:0010533	60.88	gold quality
lung	UBERON:0002048	56.47	gold quality
kidney	UBERON:0002113	56.38	gold quality
left testis	UBERON:0004533	55.41	gold quality
testis	UBERON:0000473	54.20	gold quality
right testis	UBERON:0004534	53.78	gold quality
ganglionic eminence	UBERON:0004023	52.21	gold quality
cortex of kidney	UBERON:0001225	52.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	51.79	gold quality
cortical plate	UBERON:0005343	49.30	gold quality
skin of leg	UBERON:0001511	48.82	gold quality
superior frontal gyrus	UBERON:0002661	48.36	gold quality
zone of skin	UBERON:0000014	47.93	gold quality
skin of abdomen	UBERON:0001416	47.39	gold quality
primary visual cortex	UBERON:0002436	46.68	gold quality
endocervix	UBERON:0000458	44.24	gold quality
mucosa of stomach	UBERON:0001199	44.16	gold quality
duodenum	UBERON:0002114	43.96	gold quality
adenohypophysis	UBERON:0002196	43.34	gold quality
right frontal lobe	UBERON:0002810	42.56	gold quality
pituitary gland	UBERON:0000007	41.80	gold quality
cerebellar hemisphere	UBERON:0002245	41.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.61

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), GGTLC1 (ENSG00000149435), GGT6 (ENSG00000167741)

Protein

Protein identifiers

Glutathione hydrolase light chain 3 — B5MD39 (reviewed: B5MD39)

Alternative names: Gamma-glutamyltransferase light chain 3

All UniProt accessions (1): B5MD39

UniProt curated annotations — full annotation on UniProt →

Function. Likely to be catalytically inactive.

Miscellaneous. Corresponds to the light chain of other gamma-glutamyltransferase family members.

Similarity. Belongs to the gamma-glutamyltransferase family.

RefSeq proteins (1): NP_001342408* (*=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 (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-B5MD39-F1	92.84	0.79

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: 27 (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 (1): glutathione gamma-glutamate hydrolase (GO:0036374)

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
extracellular vesicle	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGTLC3	GGT6	Q6P531	801
GGTLC3	AGA	P20933	797
GGTLC3	GGCT	O75223	720
GGTLC3	GLYAT	Q6IB77	609
GGTLC3	GPT	P24298	603
GGTLC3	GUCY2C	P25092	574
GGTLC3	DOCK11	Q5JSL3	529
GGTLC3	ALB	P02768	459
GGTLC3	TCTA	P57738	447
GGTLC3	GPT2	Q8TD30	438
GGTLC3	ADIPOQ	Q15848	437
GGTLC3	GLS	O94925	423
GGTLC3	TSHZ1	Q6ZSZ6	399
GGTLC3	CRP	P02741	391
GGTLC3	TRIO	O75962	375

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350

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, O05218, P15557, Q05053, Q51693, Q6P531, Q6IE08, A7YWM1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997057	GRCh37/hg19 22q11.21(chr22:18909044-21464119)	Pathogenic

SpliceAI

776 predictions. Top by Δscore:

Variant	Effect	Δscore
22:18516947:CCCA:C	donor_loss	1.0000
22:18516948:CCAC:C	donor_loss	1.0000
22:18516949:CACC:C	donor_loss	1.0000
22:18516950:ACCTG:A	donor_loss	1.0000
22:18516951:C:CT	donor_loss	1.0000
22:18516968:T:A	donor_gain	1.0000
22:18517046:C:CT	acceptor_gain	1.0000
22:18517062:TGGC:T	acceptor_gain	1.0000
22:18517064:GCCT:G	acceptor_loss	1.0000
22:18517066:C:CC	acceptor_gain	1.0000
22:18517067:T:G	acceptor_loss	1.0000
22:18517142:CATA:C	donor_loss	1.0000
22:18517144:TACCA:T	donor_loss	1.0000
22:18517145:A:AC	donor_gain	1.0000
22:18517145:A:T	donor_loss	1.0000
22:18517146:C:CC	donor_gain	1.0000
22:18517258:CC:C	acceptor_gain	1.0000
22:18517259:CC:C	acceptor_gain	1.0000
22:18517260:C:CC	acceptor_gain	1.0000
22:18517264:G:T	acceptor_gain	1.0000
22:18517266:CCGA:C	acceptor_gain	1.0000
22:18517267:C:T	acceptor_gain	1.0000
22:18517267:CGA:C	acceptor_gain	1.0000
22:18517268:G:T	acceptor_gain	1.0000
22:18517269:A:AC	acceptor_gain	1.0000
22:18517269:A:C	acceptor_gain	1.0000
22:18517720:A:AC	donor_gain	1.0000
22:18517721:C:CC	donor_gain	1.0000
22:18517761:T:TA	donor_gain	1.0000
22:18518083:C:CA	donor_gain	1.0000

AlphaMissense

1459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:18517736:G:C	S54R	0.910
22:18517736:G:T	S54R	0.910
22:18517738:T:G	S54R	0.910
22:18517042:G:C	F147L	0.881
22:18517042:G:T	F147L	0.881
22:18517044:A:G	F147L	0.881
22:18517486:A:C	F60L	0.873
22:18517486:A:T	F60L	0.873
22:18517488:A:G	F60L	0.873
22:18517811:G:C	F29L	0.864
22:18517811:G:T	F29L	0.864
22:18517813:A:G	F29L	0.864
22:18516528:C:A	R217S	0.861
22:18516528:C:G	R217S	0.861
22:18517773:A:T	V42D	0.856
22:18516542:C:G	A213P	0.852
22:18516544:G:T	A212D	0.834
22:18517770:A:T	V43D	0.832
22:18517779:A:G	L40P	0.827
22:18517753:C:G	A49P	0.824
22:18516529:C:A	R217M	0.823
22:18517752:G:T	A49D	0.822
22:18516512:C:G	A223P	0.821
22:18516575:C:G	A202P	0.816
22:18516551:A:G	W210R	0.815
22:18516551:A:T	W210R	0.815
22:18516534:G:C	D215E	0.803
22:18516534:G:T	D215E	0.803
22:18516536:C:G	D215H	0.800
22:18517749:A:T	V50E	0.800

dbSNP variants (sampled 300 via entrez): RS1000578830 (22:18516270 TC>T), RS1008983001 (22:18516708 T>C), RS1014265155 (22:18518857 C>A,T), RS1027839568 (22:18517053 T>G), RS1043680032 (22:18518084 C>T), RS1046621727 (22:18518889 T>C), RS1047357664 (22:18518723 G>A), RS1053219843 (22:18516393 A>C,G), RS1053570562 (22:18519650 G>A), RS111275698 (22:18519240 G>A,C), RS112912641 (22:18518482 A>C), RS1156805909 (22:18518178 C>CA), RS1156829222 (22:18517818 GGC>G), RS1159018239 (22:18519261 A>C), RS1159258685 (22:18517291 G>A)

Disease associations

OMIM: gene MIM:612340 | disease phenotypes: MIM:219050

GenCC curated gene-disease

Mondo (1): cryptorchidism (MONDO:0009047)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
coumarin	affects phosphorylation	1
Zoledronic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02110745	PHASE4	COMPLETED	The Effect of Induction Technique on Postoperative Pain and Agitation
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT01701778	PHASE2	COMPLETED	Caudal Versus Intravenous Dexmedetomidine for Supplementation of Caudal Analgesia in Children
NCT00253253	Not specified	COMPLETED	Long-Term Outcome in Congenital Undescended Testis After Surgical Treatment by Orchidopexy
NCT00264121	Not specified	UNKNOWN	The Incidence of Congenital Undescended Testis Among Dutch Infants
NCT00435383	Not specified	COMPLETED	Comparing Oxygen Saturation in Post Anesthesia Care Unit After Different Methods of Pain Relief
NCT00565513	Not specified	COMPLETED	Cryptorchidism: Impact of in Utero Exposure to Xenobiotics With Hormonal Action
NCT01604915	Not specified	COMPLETED	Comparison of Dexamethasone Added to Ropivacaine and Ropivacaine Alone in Caudal Analgesia in Children Undergoing Orchiopexy
NCT01896076	Not specified	COMPLETED	The Caudal Space in Children: Ultrasound Evaluation
NCT02040389	Not specified	COMPLETED	Visual Guidelines and Tutoring in Pediatric Urological Surgery
NCT02249637	Not specified	COMPLETED	A Novel Technique of Circumcision Incision Orchidopexy
NCT02731989	Not specified	UNKNOWN	Comparison Between the Clinical Assessment of the Undescended Testis and Its’ Ultrasonographic Size
NCT02936024	Not specified	UNKNOWN	One Stage vs. Two Stage Gubernaculum Sparing Laparoscopic Orchidopexy (GSLO)
NCT03575377	Not specified	COMPLETED	Opioid Use, Storage, and Disposal Among Pediatric Patients After Surgery
NCT03677453	Not specified	COMPLETED	Interactive Perioperative Teaching Platform (IPTP)
NCT04342026	Not specified	RECRUITING	Role of the Environment and Endocrine Disruptors in Child Cryptorchidism
NCT04528381	Not specified	UNKNOWN	Role of Laparoscopy in Management of Non-palpable Undescended Testis : Assuit University Experience
NCT05097820	Not specified	RECRUITING	Prospective Observational Study on SEBBIN Silicone Gel-filled Testicular Implants
NCT05558748	Not specified	UNKNOWN	Comparison of USG-Guided Caudal Versus Ilioinguinal/Iliohypogastric Nerve Block for Pediatric Inguinal Surgeries
NCT06187844	Not specified	UNKNOWN	Value of Inguinal Exploration for Impalpable Testes
NCT06533306	Not specified	COMPLETED	Metachronous Acquired Contralateral Cryptorchidism in Patients With a History of Unilateral Cryptorchidism.
NCT06558994	Not specified	RECRUITING	Transection Versus Ligation of Internal Spermatic Vessels in Laparoscopic Fowler-Stephens Orchidopexy
NCT06560086	Not specified	UNKNOWN	Ketoconazole Contributes to Cryptorchidism Outcome Via Modulating Macrophage Trem2
NCT06698081	Not specified	RECRUITING	The Effect of Using Multimedia During the Informed Consent Process on the Anxiety of Parents of Orchiopexy Patients
NCT06862258	Not specified	NOT_YET_RECRUITING	Shehata Technique in the Treatment of Intra-abdominal Testis
NCT07106502	Not specified	NOT_YET_RECRUITING	Learning to Palpate the Child’s Testicles Using Simulation
NCT07233265	Not specified	RECRUITING	Comparison of Single Incision Scrotal vs Standard Two Incision Inguinal Orchidopexy in Children Under 10 Years.
NCT07315737	Not specified	COMPLETED	Could miRNAs be Used as Markers for Distinguishing Undescended Testicles From Retractile Testicles
NCT07319637	Not specified	COMPLETED	Comparing Two Types of Surgery for Children With Undescended Testicles When the Hernia Sac Is Tied or Not
NCT07426796	Not specified	RECRUITING	Comparison of Posterior QLB and QIPB in Pediatric Undescended Testis Surgery.
NCT07586332	Not specified	ACTIVE_NOT_RECRUITING	INVESTIGATION OF THE GENETIC ETIOLOGY OF HERNIA SAC DEVELOPMENT IN MALE CHILDREN WITH UNDESCENDED TESTIS AND INGUINAL HERNIA