GGCT

Summary

GGCT (gamma-glutamylcyclotransferase, HGNC:21705) is a protein-coding gene on chromosome 7p14.3, encoding Gamma-glutamylcyclotransferase (O75223). Catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis.

The protein encoded by this gene catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides, the penultimate step in glutathione catabolism, and may play a critical role in glutathione homeostasis. The encoded protein may also play a role in cell proliferation, and the expression of this gene is a potential marker for cancer. Pseudogenes of this gene are located on the long arm of chromosome 5 and the short arm of chromosomes 2 and 20. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 79017 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• MANE Select transcript: NM_024051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21705
Approved symbol	GGCT
Name	gamma-glutamylcyclotransferase
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC3077, CRF21, Ggc
Ensembl gene	ENSG00000006625
Ensembl biotype	protein_coding
OMIM	137170
Entrez	79017

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 nonsense_mediated_decay

ENST00000005374, ENST00000275428, ENST00000409144, ENST00000409390, ENST00000409436, ENST00000426081, ENST00000440082, ENST00000447901, ENST00000912164, ENST00000912165

RefSeq mRNA: 4 — MANE Select: NM_024051 NM_001199815, NM_001199816, NM_001199817, NM_024051

CCDS: CCDS5428, CCDS56474, CCDS56475, CCDS56476

Canonical transcript exons

ENST00000275428 — 4 exons

Exon	Start	End
ENSE00001667222	30504569	30504829
ENSE00003491459	30496621	30497235
ENSE00003525042	30500536	30500681
ENSE00003761632	30498803	30498938

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.6315 / max 421.0361, expressed in 1806 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83441	27.9279	1801
83442	2.1943	1178
83440	0.5093	265

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mammalian vulva	UBERON:0000997	99.23	gold quality
esophagus squamous epithelium	UBERON:0006920	99.21	gold quality
penis	UBERON:0000989	99.02	gold quality
secondary oocyte	CL:0000655	99.01	gold quality
oocyte	CL:0000023	98.75	gold quality
endometrium epithelium	UBERON:0004811	98.56	gold quality
epithelium of esophagus	UBERON:0001976	98.36	gold quality
tongue squamous epithelium	UBERON:0006919	98.25	gold quality
gingival epithelium	UBERON:0001949	98.20	gold quality
upper arm skin	UBERON:0004263	98.20	gold quality
corpus epididymis	UBERON:0004359	98.09	gold quality
upper leg skin	UBERON:0004262	97.82	gold quality
hair follicle	UBERON:0002073	97.70	gold quality
gingiva	UBERON:0001828	97.65	gold quality
squamous epithelium	UBERON:0006914	97.34	gold quality
pharyngeal mucosa	UBERON:0000355	97.26	gold quality
epithelium of nasopharynx	UBERON:0001951	97.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.00	gold quality
germinal epithelium of ovary	UBERON:0001304	96.85	gold quality
middle temporal gyrus	UBERON:0002771	96.79	gold quality
colonic mucosa	UBERON:0000317	96.69	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.61	gold quality
oral cavity	UBERON:0000167	96.60	gold quality
superior surface of tongue	UBERON:0007371	96.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.19	gold quality
tongue	UBERON:0001723	96.16	gold quality
body of tongue	UBERON:0011876	96.07	gold quality
frontal pole	UBERON:0002795	96.04	gold quality
parietal pleura	UBERON:0002400	96.01	gold quality
esophagus mucosa	UBERON:0002469	95.94	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	508.92
E-GEOD-125970	yes	23.45
E-CURD-112	yes	11.38
E-ANND-3	yes	10.48
E-MTAB-9689	no	271.28
E-GEOD-110499	no	261.56
E-HCAD-6	no	178.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting GGCT, 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-548C-3P	99.99	74.01	7587
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-632	96.08	67.17	798

Literature-anchored findings (GeneRIF, showing 21)

• CRF21 might play an important role in the induction of apoptosis by GGO in leukemia U937 cells. (PMID:16765912)
• presence of extra electron density/ligands and conservation at the sequence and structure levels, it is likely that the cavity has a crucial role in the function of LOC79017 and its structural neighbors possibly as an active site or ligand-binding site (PMID:17932939)
• The GGCT gene is located on chromosome 7p14-15 and consists of four exons that span 8 kb, the primary sequence is 188 amino acids in length and is unlike any protein of known function (PMID:18515354)
• C7orf24 overexpression defines a subgroup of breast tumors with poor clinical outcome. (PMID:20527979)
• GGCT may be a biomarker of tumors in a limited range of organs. (PMID:22205682)
• C7orf24 has been recognized as a potent marker for bladder and breast cancers. Studies on the role of gamma-glutamylcyclotransferace may aid in the control of malignant transformation of these cancers. (PMID:23513927)
• Transcriptional silencing of the C7orf24 gene in the non-malignant cells is elicited through heterochromatin formation in its promoter region. (PMID:23853312)
• increased expression of GGCT was a common event among invasive esophageal squamous cell carcinoma tissues regardless of the depth of invasion. Lymph node metastasis and tumor differentiation correlated with GGCT expression (PMID:24342434)
• G6PD, GGCT, IDH1, isocitrate dehydrogenase 2 (NADP+,mitochondrial) (IDH2) and glutathione S-transferase pi 1(GSTP1), five of the critical components of GSH pathway, contribute to chemoresistance. (PMID:25818003)
• GGCT plays a critical role in lung cancer cell proliferation. (PMID:25941902)
• GGCT is promising as a diagnostic marker and a therapeutic target for various cancers. This review summarizes these interesting findings. (PMID:26339607)
• GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target. (PMID:26828272)
• Taken together, the results indicate that PHB2 plays a central role in p21 upregulation following GGCT knockdown and as such may promote deregulated proliferation of cancer cells by suppressing p21. (PMID:29307834)
• GGCT is highly upregulated in HGSC tissues and associated with FIGO stage, lymph node metastasis and ascitic fluid volume. High expression of GGCT is associated with poor survival in HGSC patients. (PMID:29429592)
• a role for EP2/EP4 signaling in regulating IGF-1-induced cell proliferation, in which EP2/EP4 signaling represses IGF-1-induced GGCT expression, is reported. (PMID:31217077)
• FOXO3a is identified as a mediator for p21 upregulation by GGCT depletion. AMPK is required for the FOXO3a-mediated p21 upregulation by GGCT depletion. AMPK-FOXO3a-p21 axis plays a role in cancer cell growth inhibition by GGCT depletion. (PMID:31345573)
• gamma-Glutamyl cyclotransferase contributes to endometrial carcinoma malignant progression and upregulation of PD-L1 expression during activation of epithelial-mesenchymal transition. (PMID:31757677)
• miR-877 inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting gamma-glutamylcyclotransferase. (PMID:34121038)
• [The expression of GGCT in the bladder urothelial cell carcinoma and its clinical significance]. (PMID:34794221)
• MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44. (PMID:35213720)
• Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer. (PMID:36233293)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ggctb	ENSDARG00000005085
mus_musculus	Ggct	ENSMUSG00000002797
rattus_norvegicus	Ggct	ENSRNOG00000034084
drosophila_melanogaster	CG4306	FBGN0036787
drosophila_melanogaster	CG32196	FBGN0052196
caenorhabditis_elegans		WBGENE00016629

Protein

Protein identifiers

Gamma-glutamylcyclotransferase — O75223 (reviewed: O75223)

Alternative names: Cytochrome c-releasing factor 21

All UniProt accessions (5): O75223, A0A090N7V5, A0A0B4J1Y4, B8ZZK2, H7BZK5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis. Induces release of cytochrome c from mitochondria with resultant induction of apoptosis.

Subunit / interactions. Homodimer.

Induction. By geranylgeraniol.

Similarity. Belongs to the gamma-glutamylcyclotransferase family.

Isoforms (4)

UniProt ID	Names	Canonical?
O75223-1	1	yes
O75223-2	2
O75223-3	3
O75223-4	4

RefSeq proteins (4): NP_001186744, NP_001186745, NP_001186746, NP_076956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013024	GGCT-like	Domain
IPR017939	G-Glutamylcylcotransferase	Family
IPR036568	GGCT-like_sf	Homologous_superfamily

Pfam: PF13772

Enzyme classification (BRENDA):

• EC 4.3.2.9 — gamma-glutamylcyclotransferase (BRENDA: 13 organisms, 119 substrates, 12 inhibitors, 54 Km, 28 kcat entries)

Substrate kinetics (BRENDA)

42 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5-L-GLUTAMYL-L-ALPHA-AMINOBUTYRATE	6–12	4
GAMMA-GLUTAMYL-L-ALANINE	2–8	4
5-L-GLUTAMYL-L-ALANINE	2–4.48	3
GLUTATHIONE	1.7–4.96	3
5-L-GLUTAMYL-L-GLUTAMINE	10–18	2
GAMMA-L-GLU-EPSILON-N-BENZYLOXYCARBONYL-L-LYS	0.28–0.32	2
2-AMINO-5-(BUTAN-2-YLAMINO)-5-OXOPENTANOIC ACID	0.07	1
2-AMINO-5-(CYCLOHEXYLAMINO)-5-OXOPENTANOIC ACID	0.061	1
2-AMINO-5-(CYCLOPROPYLAMINO)-5-OXOPENTANOIC ACID	0.045	1
2-AMINO-5-(TERT-BUTYLAMINO)-5-OXOPENTANOIC ACID	0.012	1
2-AMINO-5-OXO-5-(PROPAN-2-YLAMINO)PENTANOIC ACID	0.068	1
2-AMINO-5-[(2-METHYLBUTYL)AMINO]-5-OXOPENTANOIC	0.19	1
2-AMINO-5-[(2S)-BUTAN-2-YLAMINO]-5-OXOPENTANOIC	0.11	1
2-AMINO-5-[[(2S)-2-METHYLBUTYL]AMINO]-5-OXOPENTA	0.21	1
5-L-(THREO-2-METHYL)GLUTAMYL-L-ALPHA-AMINOBUTYRA	5	1

Catalyzed reactions (Rhea), 1 shown:

• an alpha-(gamma-L-glutamyl)-L-amino acid = 5-oxo-L-proline + an L-alpha-amino acid (RHEA:20505)

UniProt features (28 total): helix 8, strand 6, mutagenesis site 4, splice variant 4, binding site 2, chain 1, active site 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3CRY	X-RAY DIFFRACTION	1.7
2I5T	X-RAY DIFFRACTION	2.01
2Q53	X-RAY DIFFRACTION	2.01
2RBH	X-RAY DIFFRACTION	2.1
2PN7	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75223-F1	93.67	0.90

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): 98 (proton acceptor)

Ligand- & substrate-binding residues (2): 19–24; 139

Post-translational modifications (1): 173

Mutagenesis-validated functional residues (4):

Position	Phenotype
98	abolishes activity without altering structure.
105	marked decrease in catalytic efficiency and specific activity.
125	little or no change in reaction kinetics.
23	marked decrease in catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-174403	Glutathione synthesis and recycling

MSigDB gene sets: 160 (showing top): MORF_MTA1, REACTOME_BIOLOGICAL_OXIDATIONS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, WEI_MYCN_TARGETS_WITH_E_BOX, MORF_SKP1A, GOBP_APOPTOTIC_SIGNALING_PATHWAY, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, MORF_ATOX1, GOBP_RELEASE_OF_CYTOCHROME_C_FROM_MITOCHONDRIA, WEST_ADRENOCORTICAL_CARCINOMA_VS_ADENOMA_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, REACTOME_GLUTATHIONE_CONJUGATION, WANG_TARGETS_OF_MLL_CBP_FUSION_DN, FISCHER_DREAM_TARGETS

GO Biological Process (1): release of cytochrome c from mitochondria (GO:0001836)

GO Molecular Function (3): gamma-glutamylcyclotransferase activity (GO:0003839), protein homodimerization activity (GO:0042803), lyase activity (GO:0016829)

GO Cellular Component (2): cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glutathione conjugation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic mitochondrial changes	1
apoptotic signaling pathway	1
amidine-lyase activity	1
identical protein binding	1
protein dimerization activity	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGCT	AGA	P20933	845
GGCT	PLEKHF1	Q96S99	840
GGCT	GUCY2C	P25092	816
GGCT	GLYAT	Q6IB77	780
GGCT	TSHZ1	Q6ZSZ6	736
GGCT	GGTLC3	B5MD39	720
GGCT	GLS	O94925	701
GGCT	GGT2P	P36268	696
GGCT	GGT1	P19440	661
GGCT	OPLAH	O14841	629
GGCT	DOCK11	Q5JSL3	544
GGCT	TRIO	O75962	514
GGCT	SBSN	Q6UWP8	501
GGCT	CYCS	P00001	499
GGCT	NDUFB2	O95178	473
GGCT	CHAC1	Q9BUX1	473

IntAct

31 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GGCT	CARM1	psi-mi:“MI:0915”(physical association)	0.400
STK4	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
TSNAX		psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
GSK3A	PRSS37	psi-mi:“MI:0914”(association)	0.350
GSK3B	PRSS37	psi-mi:“MI:0914”(association)	0.350
TDRKH	GGCT	psi-mi:“MI:0914”(association)	0.350
WRAP73	GGCT	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
MSH2	GGCT	psi-mi:“MI:0914”(association)	0.350
KRAS	ARPC1B	psi-mi:“MI:0914”(association)	0.350
RBBP4	KPNA3	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ASB9	A2ML1	psi-mi:“MI:0914”(association)	0.350
MYB	A2ML1	psi-mi:“MI:0914”(association)	0.350
CTNNA1	MYO1G	psi-mi:“MI:0914”(association)	0.350
SOX2	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
GATA2	EFCAB5	psi-mi:“MI:0914”(association)	0.350
RASSF7	GGCT	psi-mi:“MI:0914”(association)	0.350
RASSF9	CCDC85C	psi-mi:“MI:0914”(association)	0.350
RASSF10	CCDC85C	psi-mi:“MI:0914”(association)	0.350
EGFR	GGCT	psi-mi:“MI:0914”(association)	0.350
SUPV3L1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (91): GGCT (Affinity Capture-MS), GGCT (Affinity Capture-MS), GGCT (Affinity Capture-MS), ITPA (Co-fractionation), SCLY (Co-fractionation), WDR1 (Co-fractionation), GGCT (Affinity Capture-MS), GGCT (Synthetic Lethality), GGCT (Affinity Capture-MS), GGCT (Affinity Capture-MS), GGCT (Affinity Capture-MS), GGCT (Affinity Capture-MS), GGCT (Affinity Capture-MS), GGCT (Proximity Label-MS), GGCT (Affinity Capture-MS)

ESM2 similar proteins: A3KNL6, A8E534, B3STU3, E0CTF3, F6HH45, O75223, O95568, P61801, Q08J23, Q0IIH4, Q28C69, Q2KIJ2, Q32LE4, Q3BCR0, Q3BCR2, Q3BCR3, Q3BCR9, Q4KM84, Q4KM86, Q4KMJ1, Q5PPV4, Q5R699, Q5SPB6, Q5ZI66, Q5ZIW7, Q641Z5, Q66I06, Q66KX0, Q6EIC1, Q6PZ05, Q7T287, Q7ZU92, Q84MC1, Q84QC1, Q8C9S8, Q8GXF0, Q8GY54, Q8R3J5, Q8RX28, Q8VYW1

Diamond homologs: O75223, Q32LE4, Q9D7X8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

750 predictions. Top by Δscore:

Variant	Effect	Δscore
7:30497246:T:TC	acceptor_gain	1.0000
7:30500581:C:CA	donor_gain	1.0000
7:30504564:CTCA:C	donor_loss	1.0000
7:30504565:TCA:T	donor_loss	1.0000
7:30504566:CACC:C	donor_loss	1.0000
7:30504567:A:AC	donor_gain	1.0000
7:30504567:ACC:A	donor_loss	1.0000
7:30504568:C:CC	donor_gain	1.0000
7:30504568:CCTG:C	donor_gain	1.0000
7:30497232:TAAT:T	acceptor_gain	0.9900
7:30497235:TC:T	acceptor_loss	0.9900
7:30497236:C:A	acceptor_loss	0.9900
7:30497236:C:CC	acceptor_gain	0.9900
7:30497236:CTGGA:C	acceptor_loss	0.9900
7:30497237:T:A	acceptor_loss	0.9900
7:30497237:T:C	acceptor_loss	0.9900
7:30497242:A:AC	acceptor_gain	0.9900
7:30497242:A:C	acceptor_gain	0.9900
7:30497245:G:C	acceptor_gain	0.9900
7:30497246:T:C	acceptor_gain	0.9900
7:30498797:GCTT:G	donor_loss	0.9900
7:30498798:CTTA:C	donor_loss	0.9900
7:30498798:CTTAC:C	donor_loss	0.9900
7:30498799:TTA:T	donor_loss	0.9900
7:30498799:TTAC:T	donor_loss	0.9900
7:30498800:TACC:T	donor_loss	0.9900
7:30498800:TACCT:T	donor_loss	0.9900
7:30498801:A:AT	donor_loss	0.9900
7:30498801:ACCTT:A	donor_loss	0.9900
7:30498802:C:A	donor_loss	0.9900

AlphaMissense

1244 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:30500664:A:C	F53L	0.995
7:30500664:A:T	F53L	0.995
7:30500666:A:G	F53L	0.995
7:30498854:A:C	S124R	0.992
7:30498854:A:T	S124R	0.992
7:30498856:T:G	S124R	0.992
7:30498860:A:C	C122W	0.992
7:30497180:A:G	L160S	0.989
7:30500573:A:G	W84R	0.989
7:30500573:A:T	W84R	0.989
7:30500617:G:T	A69D	0.988
7:30504635:G:C	N25K	0.988
7:30504635:G:T	N25K	0.988
7:30504650:A:C	F20L	0.988
7:30504650:A:T	F20L	0.988
7:30504652:A:G	F20L	0.988
7:30497204:A:G	L152S	0.986
7:30500582:C:G	G81R	0.986
7:30500582:C:T	G81R	0.986
7:30504633:A:G	L26P	0.986
7:30500571:C:A	W84C	0.985
7:30500571:C:G	W84C	0.985
7:30498811:A:G	Y139H	0.984
7:30498858:C:G	R123P	0.984
7:30504638:G:C	S24R	0.984
7:30504638:G:T	S24R	0.984
7:30504640:T:G	S24R	0.984
7:30498861:C:T	C122Y	0.983
7:30498862:A:G	C122R	0.983
7:30500581:C:T	G81E	0.983

dbSNP variants (sampled 300 via entrez): RS1000081672 (7:30506493 G>A), RS1000630186 (7:30506809 T>C,G), RS1000729865 (7:30501299 A>G), RS1000801711 (7:30501465 C>G), RS1000916490 (7:30506654 C>A,T), RS1001142087 (7:30505137 T>C), RS1001349335 (7:30498397 T>A), RS1001401809 (7:30498076 G>A,C), RS1001574860 (7:30503957 C>CT), RS1001652850 (7:30505032 T>C,G), RS1001809400 (7:30498420 T>C), RS1001860064 (7:30505101 A>C,G,T), RS1001975366 (7:30497383 T>C), RS1002232831 (7:30505552 A>G), RS1002315340 (7:30504945 G>A,C,T)

Disease associations

OMIM: gene MIM:137170 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067016 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Leukotriene and lipoxin metabolism

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
acivicin	Inhibition	6.15	pIC50
GGsTop	Inhibition	3.77	pKi

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	3
sodium arsenite	decreases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Benztropine	affects cotreatment, decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Coumestrol	increases expression, affects cotreatment	1
Cuprizone	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651470	Binding	Binding affinity to human GGCT incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice