G2E3

Summary

G2E3 (G2/M-phase specific E3 ubiquitin protein ligase, HGNC:20338) is a protein-coding gene on chromosome 14q12, encoding G2/M phase-specific E3 ubiquitin-protein ligase (Q7L622). E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in apoptotic process and protein ubiquitination. Predicted to act upstream of or within blastocyst development; negative regulation of intrinsic apoptotic signaling pathway; and protein polyubiquitination. Located in Golgi apparatus and cytosol.

Source: NCBI Gene 55632 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_017769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20338
Approved symbol	G2E3
Name	G2/M-phase specific E3 ubiquitin protein ligase
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20333, PHF7B
Ensembl gene	ENSG00000092140
Ensembl biotype	protein_coding
OMIM	611299
Entrez	55632

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000206595, ENST00000438909, ENST00000544007, ENST00000547532, ENST00000547638, ENST00000548934, ENST00000549159, ENST00000549553, ENST00000550944, ENST00000552488, ENST00000552515, ENST00000553504, ENST00000554714, ENST00000555429, ENST00000648008, ENST00000878880, ENST00000930374, ENST00000930375, ENST00000930376

RefSeq mRNA: 2 — MANE Select: NM_017769 NM_001308097, NM_017769

CCDS: CCDS76669, CCDS9638

Canonical transcript exons

ENST00000206595 — 15 exons

Exon	Start	End
ENSE00001093147	30616278	30620064
ENSE00001650715	30559158	30559272
ENSE00001666956	30607888	30608069
ENSE00003487409	30597420	30597526
ENSE00003505403	30612207	30612379
ENSE00003565308	30605505	30605812
ENSE00003590679	30598483	30598599
ENSE00003603766	30601999	30602131
ENSE00003622300	30581076	30581116
ENSE00003634415	30601770	30601894
ENSE00003640936	30615349	30615539
ENSE00003685277	30586718	30586815
ENSE00003786266	30589383	30589484
ENSE00003788830	30593474	30593639
ENSE00003791106	30592323	30592447

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 96.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1400 / max 406.6553, expressed in 1755 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139091	14.3731	1746
139090	0.7137	429
139093	0.0389	3
139092	0.0143	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.25	gold quality
ventricular zone	UBERON:0003053	91.69	gold quality
right testis	UBERON:0004534	91.23	gold quality
testis	UBERON:0000473	90.89	gold quality
left testis	UBERON:0004533	90.81	gold quality
embryo	UBERON:0000922	89.68	gold quality
ganglionic eminence	UBERON:0004023	89.68	gold quality
epithelial cell of pancreas	CL:0000083	88.95	gold quality
colonic epithelium	UBERON:0000397	88.89	gold quality
cortical plate	UBERON:0005343	88.10	gold quality
calcaneal tendon	UBERON:0003701	87.92	gold quality
tibialis anterior	UBERON:0001385	87.79	gold quality
secondary oocyte	CL:0000655	86.63	gold quality
bone marrow cell	CL:0002092	86.60	gold quality
adrenal tissue	UBERON:0018303	86.25	gold quality
pancreatic ductal cell	CL:0002079	85.09	gold quality
thymus	UBERON:0002370	84.42	gold quality
oocyte	CL:0000023	83.79	gold quality
oviduct epithelium	UBERON:0004804	83.79	gold quality
ileal mucosa	UBERON:0000331	83.76	gold quality
bone marrow	UBERON:0002371	83.17	gold quality
stromal cell of endometrium	CL:0002255	82.84	gold quality
deltoid	UBERON:0001476	82.23	silver quality
islet of Langerhans	UBERON:0000006	82.13	gold quality
endothelial cell	CL:0000115	82.09	gold quality
tibia	UBERON:0000979	82.06	gold quality
endometrium	UBERON:0001295	82.00	gold quality
lymph node	UBERON:0000029	81.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.96
E-CURD-89	no	133.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting G2E3, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 3)

• Cell cycle phase-specific expression and highly regulated subcellular localization of G2E3 suggest a possible role in cell cycle regulation and the cellular response to DNA damage. (PMID:17239372)
• Results suggest that G2E3 is a molecular determinant of the DDR and cell survival. (PMID:25593194)
• Comprehensive analysis of the expression, prognostic significance, and regulation pathway of G2E3 in breast cancer. (PMID:36517818)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	g2e3	ENSDARG00000001313
danio_rerio	si:ch211-37e10.1	ENSDARG00000055506
danio_rerio	si:ch211-57f7.7	ENSDARG00000093131
mus_musculus	G2e3	ENSMUSG00000035293
rattus_norvegicus	G2e3	ENSRNOG00000004232
drosophila_melanogaster	pie	FBGN0005683
drosophila_melanogaster	Phf7	FBGN0031091

Paralogs (3): PHF7 (ENSG00000010318), PHF11 (ENSG00000136147), PHF6 (ENSG00000156531)

Protein

Protein identifiers

G2/M phase-specific E3 ubiquitin-protein ligase — Q7L622 (reviewed: Q7L622)

Alternative names: G2/M phase-specific HECT-type E3 ubiquitin transferase

All UniProt accessions (10): Q7L622, A0A3B3ISH7, F5GX24, F8VY49, F8W0F5, G3V3B6, G3V483, G3V5B6, H0YH90, H0YI49

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Essential in early embryonic development to prevent apoptotic death.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Predominantly expressed in brain, liver, kidney, testes and ovary.

Domain organisation. Ubiquitin ligase activity is mediated by two distinct domains, PHD-type zinc fingers 2 and 3. The use of these distinct domains may allow ubiquitination of different targets by each domain. The HECT domain is catalytically inactive and does not contribute to this activity.

Induction. Up-regulated approximately 4-fold in G2 when compared to S phase. Down-regulated approximately 3-fold by gamma-irradiation.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (2): NP_001295026, NP_060239* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000569	HECT_dom	Domain
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR034732	EPHD	Domain
IPR035983	Hect_E3_ubiquitin_ligase	Homologous_superfamily
IPR042013	PHF7/G2E3_ePHD	Domain
IPR051188	PHD-type_Zinc_Finger	Family
IPR059102	PHD_PHF7/G2E3-like	Domain

Pfam: PF00632, PF13771, PF26054

UniProt features (16 total): mutagenesis site 6, zinc finger region 4, sequence conflict 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L622-F1	85.71	0.66

Functional residue map

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

Mutagenesis-validated functional residues (6):

Position	Phenotype
258	strong activity; when associated with a-84; a-261 and a-666. no activity; when associated with a-147; a-261 and a-666. n
261	strong activity; when associated with a-84; a-258 and a-666. no activity; when associated with a-84; a-147 and a-258. no
666	no effect on subcellular location. strong activity; when associated with a-84; a-258 and a261. strong activity; when ass
30–31	loss of nucleolar localization. no effect on nuclear localization.
84	strong activity; when associated with a-258; a-261 and a-666. strong activity; when associated with a-147 and a-666. no
147	strong activity; when associated with a-84 and a-666. no activity; when associated with a-258; a-261 and a-666. no activ

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, chr14q12, WEI_MYCN_TARGETS_WITH_E_BOX, SOX9_B1, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, FISCHER_DREAM_TARGETS, SOX5_01, YAMAZAKI_TCEB3_TARGETS_DN, GOCC_NUCLEOLUS, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, TST1_01

GO Biological Process (2): apoptotic process (GO:0006915), protein ubiquitination (GO:0016567)

GO Molecular Function (6): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
protein modification by small protein conjugation	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
endomembrane system	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
G2E3	GAS2L3	Q86XJ1	611
G2E3	CKAP5	Q14008	510
G2E3	CDCA2	Q69YH5	509
G2E3	SPDYE6	P0CI01	507
G2E3	SCFD1	Q8WVM8	505
G2E3	NCAPD2	Q15021	498
G2E3	DTD2	Q96FN9	488
G2E3	CKAP2	Q8WWK9	476
G2E3	KIF20B	Q96Q89	472
G2E3	DLGAP5	Q15398	465
G2E3	MYC	P01106	441
G2E3	PRIM1	P49642	434
G2E3	PSRC1	Q6PGN9	432
G2E3	DIP2C	Q9Y2E4	425
G2E3	ANKRD46	Q86W74	422

IntAct

42 interactions, top by confidence:

A	B	Type	Score
G2E3	RPS15	psi-mi:“MI:0915”(physical association)	0.560
RPS15	G2E3	psi-mi:“MI:0915”(physical association)	0.560
G2E3	SPECC1L	psi-mi:“MI:0915”(physical association)	0.560
G2E3	ATN1	psi-mi:“MI:0915”(physical association)	0.560
G2E3		psi-mi:“MI:0915”(physical association)	0.560
G2E3	NEFL	psi-mi:“MI:0915”(physical association)	0.560
KLK6	G2E3	psi-mi:“MI:0915”(physical association)	0.560
G2E3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
G2E3	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
HTT	G2E3	psi-mi:“MI:0915”(physical association)	0.560
G2E3	SPECC1L	psi-mi:“MI:0914”(association)	0.560
G2E3	MDH2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (19): G2E3 (Two-hybrid), G2E3 (Two-hybrid), SPECC1L (Affinity Capture-MS), G2E3 (Affinity Capture-RNA), G2E3 (Affinity Capture-MS), G2E3 (Affinity Capture-MS), G2E3 (Proximity Label-MS), G2E3 (Two-hybrid), EFHD1 (Affinity Capture-MS), SPECC1L (Affinity Capture-MS), G2E3 (Affinity Capture-MS), HMGN2 (Cross-Linking-MS (XL-MS)), HIST1H1C (Cross-Linking-MS (XL-MS)), SGTA (Cross-Linking-MS (XL-MS)), RPL31 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1KXW8, A6QL50, E1BGQ2, H0Y354, O94955, P47224, Q08326, Q0IIH8, Q1JQA1, Q1RMS8, Q1RMZ1, Q2TBU5, Q3T1H6, Q4R372, Q4R528, Q4R9C4, Q5F480, Q5F4A1, Q5I0G3, Q5RCQ0, Q5RFG8, Q5TFE4, Q5TYM5, Q641X7, Q6L9T8, Q6PIP5, Q7L622, Q7Z6J8, Q7ZX59, Q86X60, Q8BFZ8, Q8BKW4, Q8BM85, Q8BX13, Q8CEL2, Q8N5C7, Q8N635, Q8NHU2, Q8TCF1, Q8TCJ0

Diamond homologs: A6H5X4, F4I443, O08550, O14686, P55200, Q03164, Q08DR0, Q2HJ93, Q4R9C4, Q5F4A1, Q5I0E2, Q5I0J8, Q5R5Z2, Q5RJY2, Q6PDK2, Q7L622, Q8BRH4, Q8BVM9, Q8IWS0, Q8NEZ4, Q9D4J7, Q9UIL8, Q9UMN6, Q61818, Q6AXW4, Q7Z5J4, Q9BWX1, Q9DAG9, Q24742, Q9EPQ8, Q9UGU0, Q9VKW2, P20659, Q6AWG9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	G2E3	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2586 predictions. Top by Δscore:

Variant	Effect	Δscore
14:30586710:A:AG	acceptor_gain	1.0000
14:30586716:A:AG	acceptor_gain	1.0000
14:30586717:G:GG	acceptor_gain	1.0000
14:30586717:GCTT:G	acceptor_gain	1.0000
14:30586811:GTTTG:G	donor_gain	1.0000
14:30586812:TTTGG:T	donor_loss	1.0000
14:30586813:TTGGT:T	donor_loss	1.0000
14:30586814:TGGT:T	donor_loss	1.0000
14:30586815:GGT:G	donor_loss	1.0000
14:30586816:GTGA:G	donor_loss	1.0000
14:30586817:TGA:T	donor_loss	1.0000
14:30586818:GAG:G	donor_loss	1.0000
14:30586819:AGTAT:A	donor_loss	1.0000
14:30589381:A:AG	acceptor_gain	1.0000
14:30589381:AGTT:A	acceptor_gain	1.0000
14:30589382:G:GG	acceptor_gain	1.0000
14:30589382:GTT:G	acceptor_gain	1.0000
14:30589382:GTTG:G	acceptor_gain	1.0000
14:30592310:C:G	acceptor_gain	1.0000
14:30592312:T:G	acceptor_gain	1.0000
14:30592446:GC:G	donor_gain	1.0000
14:30592448:G:GG	donor_gain	1.0000
14:30597527:G:GG	donor_gain	1.0000
14:30598479:ATAG:A	acceptor_loss	1.0000
14:30598480:TA:T	acceptor_loss	1.0000
14:30598481:A:AG	acceptor_gain	1.0000
14:30598481:AG:A	acceptor_loss	1.0000
14:30598482:G:GG	acceptor_gain	1.0000
14:30598482:GA:G	acceptor_gain	1.0000
14:30598482:GAGAT:G	acceptor_gain	1.0000

AlphaMissense

4672 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:30586810:T:C	C44R	0.999
14:30589437:T:C	F64L	0.999
14:30589438:T:C	F64S	0.999
14:30589439:T:A	F64L	0.999
14:30589439:T:G	F64L	0.999
14:30592362:T:C	C93R	0.999
14:30593541:T:C	C144R	0.999
14:30597456:T:C	C189R	0.999
14:30598493:T:A	W216R	0.999
14:30598493:T:C	W216R	0.999
14:30598495:G:C	W216C	0.999
14:30598495:G:T	W216C	0.999
14:30601789:T:C	C258R	0.999
14:30586812:T:G	C44W	0.998
14:30589472:A:C	R75S	0.998
14:30589472:A:T	R75S	0.998
14:30592326:T:C	C81R	0.998
14:30592362:T:A	C93S	0.998
14:30592363:G:C	C93S	0.998
14:30592377:T:C	C98R	0.998
14:30593481:T:C	C124R	0.998
14:30593543:C:G	C144W	0.998
14:30597465:T:C	C192R	0.998
14:30597507:G:A	G206R	0.998
14:30597507:G:C	G206R	0.998
14:30597508:G:A	G206E	0.998
14:30586811:G:A	C44Y	0.997
14:30589471:G:C	R75T	0.997
14:30592363:G:A	C93Y	0.997
14:30592364:T:G	C93W	0.997

dbSNP variants (sampled 300 via entrez): RS1000051154 (14:30591166 A>G), RS1000097462 (14:30613613 T>C), RS1000111851 (14:30571259 GT>G,GTT), RS1000157074 (14:30583519 G>A), RS1000168284 (14:30615217 G>A), RS1000210153 (14:30566652 C>T), RS1000305561 (14:30613805 G>A,T), RS1000376746 (14:30619303 G>T), RS1000379087 (14:30596737 G>A), RS1000382061 (14:30561476 T>A), RS1000490674 (14:30582285 A>G), RS1000542381 (14:30565359 C>A), RS1000556574 (14:30608682 A>G), RS1000604809 (14:30582554 C>G), RS1000622868 (14:30610194 T>C)

Disease associations

OMIM: gene MIM:611299 | 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
GCST003074_17	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	7.000000e-07
GCST003901_18	Cognitive decline (age-related)	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
Valproic Acid	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1

Clinical trials (associated diseases)

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