CCNG1

Summary

CCNG1 (cyclin G1, HGNC:1592) is a protein-coding gene on chromosome 5q34, encoding Cyclin-G1 (P51959). May play a role in growth regulation.

The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and CDK inhibitors. The protein encoded by this gene is a member of the cyclin family and contains the cyclin box. The encoded protein lacks the protein destabilizing (PEST) sequence that is present in other family members. Transcriptional activation of this gene can be induced by tumor protein p53. Two transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 900 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 48 total — 1 pathogenic
• MANE Select transcript: NM_004060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1592
Approved symbol	CCNG1
Name	cyclin G1
Location	5q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113328
Ensembl biotype	protein_coding
OMIM	601578
Entrez	900

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000340828, ENST00000504553, ENST00000506186, ENST00000509143, ENST00000509425, ENST00000510097, ENST00000510664, ENST00000511490, ENST00000511683, ENST00000512163, ENST00000512532, ENST00000514367, ENST00000850590, ENST00000869626, ENST00000869627, ENST00000934523, ENST00000934524, ENST00000934525, ENST00000934526, ENST00000934527, ENST00000953329

RefSeq mRNA: 9 — MANE Select: NM_004060 NM_001364015, NM_001364018, NM_001364019, NM_001364020, NM_001364021, NM_001364022, NM_001364023, NM_004060, NM_199246

CCDS: CCDS4360, CCDS93817

Canonical transcript exons

ENST00000340828 — 7 exons

Exon	Start	End
ENSE00001373666	163437595	163437804
ENSE00001884424	163443674	163445016
ENSE00003495533	163441078	163441331
ENSE00003584685	163442045	163442143
ENSE00003728048	163442374	163442568
ENSE00003738994	163441886	163441964
ENSE00003759953	163439257	163439520

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 126.6870 / max 1903.1470, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59968	124.8675	1825
59969	1.5358	676
59970	0.2838	139

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.52	gold quality
biceps brachii	UBERON:0001507	99.18	gold quality
corpus epididymis	UBERON:0004359	99.15	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.08	gold quality
jejunum	UBERON:0002115	99.07	gold quality
nephron tubule	UBERON:0001231	99.04	gold quality
caput epididymis	UBERON:0004358	99.02	gold quality
diaphragm	UBERON:0001103	98.92	gold quality
parotid gland	UBERON:0001831	98.89	gold quality
germinal epithelium of ovary	UBERON:0001304	98.87	gold quality
duodenum	UBERON:0002114	98.82	gold quality
body of pancreas	UBERON:0001150	98.80	gold quality
heart right ventricle	UBERON:0002080	98.68	gold quality
cauda epididymis	UBERON:0004360	98.50	gold quality
skeletal muscle tissue	UBERON:0001134	98.49	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.42	gold quality
choroid plexus epithelium	UBERON:0003911	98.40	gold quality
parietal pleura	UBERON:0002400	98.37	gold quality
triceps brachii	UBERON:0001509	98.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.36	gold quality
mammary duct	UBERON:0001765	98.30	gold quality
vastus lateralis	UBERON:0001379	98.27	gold quality
colonic mucosa	UBERON:0000317	98.24	gold quality
gluteal muscle	UBERON:0002000	98.23	gold quality
quadriceps femoris	UBERON:0001377	98.22	gold quality
rectum	UBERON:0001052	98.17	gold quality
seminal vesicle	UBERON:0000998	98.12	gold quality
colonic epithelium	UBERON:0000397	98.10	gold quality
deltoid	UBERON:0001476	98.10	gold quality
muscle tissue	UBERON:0002385	98.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	14.67
E-CURD-112	yes	8.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, ETS1, HMGA2, NFKB, TP53, TP73

miRNA regulators (miRDB)

95 targeting CCNG1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AZ-5P	99.83	69.94	3230

Literature-anchored findings (GeneRIF, showing 33)

• cyclin G1 has growth inhibitory activity that is mechanistically linked to ARF-p53 and pRb tumor suppressor pathways. (PMID:12556559)
• does not increase significantly during colorectal carcinogenesis and during later metastasis to lymph nodes. (PMID:12684677)
• cyclin G has a role in ATM-dependent p53 regulation and in cell cycle regulation during DNA damage (PMID:15077171)
• Cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1. (PMID:16322753)
• cyclin G1 is a target of miR-122a in human hepatocellular carcinoma (PMID:17616664)
• Review of cyclin D1 and cyclin G and CDK acitivty and their roles in cancer pathogenesis, and their proteosomal degradation pathways as targets for cancer therapy (PMID:17868090)
• Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1. (PMID:18408012)
• the cyclin box has a role in the proteasome-mediated degradation of cyclin G1 (PMID:18632610)
• The B’alpha1 subunit of the serine/threonine protein phosphatase 2A, which binds to cyclin G1, can stabilize cyclin G1 under unstressed conditions and upon DNA damage, as well as inhibit the ability of cyclin G1 to be ubiquitinated. (PMID:18981217)
• Results show that in patients resected for HCC, lower miR-122 levels were associated with a shorter TTR, whereas higher cyclin G1 expression was related to a lower survival, suggesting that miR-122 might represent an effective molecular target for HCC. (PMID:19584283)
• Low expression of P27(kip1) and the high expression of cyclin G in patients acute leukemia may have some correlation with genesis and development of the disease. (PMID:19698214)
• Expression of cyclin G1 and G2 is strongly associated with nasopharyngeal carcinoma cell differentiation. (PMID:21688120)
• Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity. (PMID:22105316)
• Cyclin G1 overexpression enhanced Akt activation through interaction with p85 (regulatory subunit of phosphoinositide 3-kinase) (PMID:22271581)
• data suggest that the deficiency of progesterone and its receptors is an important cause of the decreased expression of cyclin G1 in endometrial carcinoma, which may account for carcinogenesis and development of endometrial carcinomas (PMID:22649121)
• cyclin G1 levels were increased in normal tissue compared with hepatocellular carcinoma tissue and vary over the course of the cell cycle, with equal distribution between the nucleus and cytoplasm. (PMID:22835824)
• cyclin G1 exerts negative control on proliferation of endometrial carcinoma cells (ECCs). (PMID:23589924)
• Post-transcriptional regulation of cyclins D1, D3 and G1 and proliferation of human cancer cells depend on IMP-3 nuclear localization. (PMID:23812426)
• Progesterone-induced cyclin G1 mediates the inhibitory effect of progesterone on endometrial epithelial cell proliferation. (PMID:25007270)
• OA induced cell cycle arrest in lung cancer cells through miR-122/Cyclin G1/MEF2D pathway. This finding may contribute to the understanding of the molecular mechanism of OA’s anti-tumor activity (PMID:25472877)
• Methylation-associated miR-9 down-regulation is probably one of the key mechanisms for paclitaxel resistance in EOC cells, via targeting CCNG1. (PMID:26152689)
• Data show that the miR-27b/cyclin G1 protein (CCNG1)/p53 tumor suppressor protein (P53)/miR-508-5p axis plays important roles in gastric cancer (GC)-associated multidrug resistance (MDR). (PMID:26623719)
• Results show that miR-23b may inhibit epithelial ovarian tumorigenesis and progression by targeting CCNG1 and modulating the expression of the relevant genes. (PMID:26872615)
• our findings revealed that the C/EBPbeta-LINC01133 axis performs an oncogenic function in pancreatic ductal adenocarcinoma by activating CCNG1 (PMID:29458145)
• Low CCNG1 expression is associated with cancer. (PMID:29787434)
• miR-516b functions as a tumor suppressor by directly modulating CCNG1 expression in esophageal squamous carcinoma cells. (PMID:30119241)
• Our findings indicate that CCNG1 overexpression, which is associated with poor clinical prognosis of high-grade serous ovarian cancer(HGSOC), can promote metastasis and chemotherapy resistance via the P53mt-Notch3 pathway. Our data also suggest that CCNG1 inhibitors represent a novel approach to increase chemotherapy efficacy in HGSOC and potentially improve patient outcomes. (PMID:30565428)
• Cyclin G1 (CG1), an atypical cyclin, promoted G2-M arrest in proximal tubular cell and up-regulated target of rapamycin (TOR)-autophagy spatial coupling compartment formation. (PMID:30674655)
• MicroRNA-23a inhibits the growth of papillary thyroid carcinoma via regulating cyclin G1. (PMID:31081097)
• MicroRNA-488 inhibits ovarian cancer cell metastasis through regulating CCNG1 and p53 expression. (PMID:32271408)
• Silencing the Expression of Cyclin G1 Enhances the Radiosensitivity of Hepatocellular Carcinoma In Vitro and In Vivo by Inducing Apoptosis. (PMID:33543294)
• Long noncoding RNA OIP5AS1 facilitates the progression of ovarian cancer via the miR1283p/CCNG1 axis. (PMID:33760168)
• PRMT6 functionally associates with PRMT5 to promote colorectal cancer progression through epigenetically repressing the expression of CDKN2B and CCNG1. (PMID:36400182)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccng1	ENSDARG00000076667
mus_musculus	Ccng1	ENSMUSG00000020326
rattus_norvegicus	Ccng1	ENSRNOG00000003256
drosophila_melanogaster	CycA	FBGN0000404
drosophila_melanogaster	CycB	FBGN0000405
drosophila_melanogaster	CycD	FBGN0010315
drosophila_melanogaster	CycE	FBGN0010382
caenorhabditis_elegans		WBGENE00000863
caenorhabditis_elegans		WBGENE00000864
caenorhabditis_elegans		WBGENE00000865
caenorhabditis_elegans		WBGENE00000866
caenorhabditis_elegans	cyb-2.2	WBGENE00000867
caenorhabditis_elegans		WBGENE00000870
caenorhabditis_elegans	cye-1	WBGENE00000871
caenorhabditis_elegans		WBGENE00017259

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

Cyclin-G1 — P51959 (reviewed: P51959)

All UniProt accessions (5): P51959, D6RCC5, D6RD30, D6RGX3, E7ERZ1

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in growth regulation. Is associated with G2/M phase arrest in response to DNA damage. May be an intermediate by which p53 mediates its role as an inhibitor of cellular proliferation.

Subcellular location. Nucleus.

Tissue specificity. High levels in skeletal muscle, ovary, kidney and colon.

Induction. Activated in breast and prostate cancer cells. Activated by actinomycin-D induced DNA damage.

Similarity. Belongs to the cyclin family. Cyclin G subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P51959-1	1	yes
P51959-2	2

RefSeq proteins (9): NP_001350944, NP_001350947, NP_001350948, NP_001350949, NP_001350950, NP_001350951, NP_001350952, NP_004051, NP_954854 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR039361	Cyclin	Family

Pfam: PF00134

UniProt features (7 total): sequence conflict 3, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51959-F1	85.69	0.66

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-6806003	Regulation of TP53 Expression and Degradation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 290 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, SMITH_TERT_TARGETS_DN, NKX62_Q2, CATTTCA_MIR203, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, MARZEC_IL2_SIGNALING_DN, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION

GO Biological Process (3): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), G1/S transition of mitotic cell cycle (GO:0000082), cell division (GO:0051301)

GO Molecular Function (2): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein binding (GO:0005515)

GO Cellular Component (4): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Regulation of TP53 Expression and Degradation	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Activity	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cyclin-dependent protein serine/threonine kinase activity	2
cellular anatomical structure	2
regulation of protein serine/threonine kinase activity	1
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cellular process	1
cyclin-dependent protein kinase regulator activity	1
binding	1
serine/threonine protein kinase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2467 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNG1	TP53	P04637	984
CCNG1	GAK	O14976	944
CCNG1	CDK5	Q00535	813
CCNG1	CCNL2	Q96S94	780
CCNG1	MDM2	Q00987	741
CCNG1	TRERF1	Q96PN7	649
CCNG1	CDKN1A	P38936	616
CCNG1	CDK1	P06493	611
CCNG1	SLC7A1	P30825	609
CCNG1	GADD45A	P24522	583
CCNG1	SRSF2	Q01130	579
CCNG1	ATM	Q13315	572
CCNG1	PPM1D	O15297	551
CCNG1	NDRG3	Q9UGV2	545
CCNG1	ZMAT3	Q9HA38	533

IntAct

61 interactions, top by confidence:

A	B	Type	Score
CCNG1	TNIP1	psi-mi:“MI:0915”(physical association)	0.830
TNIP1	CCNG1	psi-mi:“MI:0915”(physical association)	0.830
PAK5	CCNG1	psi-mi:“MI:0915”(physical association)	0.670
CCNG1	PAK5	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-7	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	HMBOX1	psi-mi:“MI:0915”(physical association)	0.560
CBY2	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
KRT40	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
HMBOX1	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
TFIP11	CCNG1	psi-mi:“MI:0915”(physical association)	0.560
CCNG1	CBY2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (75): PNMA1 (Two-hybrid), TNIP1 (Two-hybrid), RBPMS (Two-hybrid), TFIP11 (Two-hybrid), PAK7 (Two-hybrid), HMBOX1 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), SPERT (Two-hybrid), KRTAP10-7 (Two-hybrid), CCNG1 (Affinity Capture-RNA), CCNG1 (Affinity Capture-RNA), CCNG1 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), CUL4B (Affinity Capture-MS)

ESM2 similar proteins: A5PK16, O08918, O42575, O96020, P24385, P24864, P25322, P30279, P30280, P30282, P39948, P39949, P39950, P41002, P47794, P48961, P49706, P49707, P50755, P50756, P51944, P51945, P51959, P53782, P55169, Q04827, Q0P5D3, Q16589, Q2KI22, Q32NJ2, Q32NM1, Q52QT8, Q5E9I1, Q5E9K7, Q5R5D0, Q5R6J5, Q5SRT8, Q5T5M9, Q5XGG5, Q61457

Diamond homologs: O08918, P13351, P24868, P24869, P25011, P25012, P25322, P30183, P30278, P30279, P30280, P39950, P46277, P46278, P51945, P51959, Q04827, Q0JIF2, Q0P5D3, Q14094, Q16589, Q39068, Q39069, Q52QT8, Q5E9I1, Q5R5D0, Q61456, Q6AY13, Q6ZMN8, Q8WNW2, Q92161, Q95TJ9, Q9Z2V9, A0MEB5, A2YH60, O01501, O42575, O48790, O93229, O96020

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TP53	“up-regulates quantity by expression”	CCNG1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58393	GRCh38/hg38 5q34(chr5:161909955-164086917)x1	Pathogenic

SpliceAI

1047 predictions. Top by Δscore:

Variant	Effect	Δscore
5:163441073:TTTA:T	acceptor_loss	1.0000
5:163441074:TTA:T	acceptor_loss	1.0000
5:163441076:A:AG	acceptor_gain	1.0000
5:163441077:G:GG	acceptor_gain	1.0000
5:163441077:GGTAC:G	acceptor_gain	1.0000
5:163441327:GAAAG:G	donor_gain	1.0000
5:163441332:G:GG	donor_gain	1.0000
5:163442042:TA:T	acceptor_loss	1.0000
5:163442043:A:AG	acceptor_gain	1.0000
5:163442043:AGC:A	acceptor_loss	1.0000
5:163442044:G:A	acceptor_loss	1.0000
5:163442044:G:GA	acceptor_gain	1.0000
5:163442044:GC:G	acceptor_gain	1.0000
5:163442044:GCC:G	acceptor_gain	1.0000
5:163442044:GCCT:G	acceptor_gain	1.0000
5:163442044:GCCTT:G	acceptor_gain	1.0000
5:163442144:G:GA	donor_loss	1.0000
5:163442145:T:G	donor_loss	1.0000
5:163443784:A:G	donor_gain	1.0000
5:163439250:T:G	acceptor_gain	0.9900
5:163439255:A:AG	acceptor_gain	0.9900
5:163439256:G:GG	acceptor_gain	0.9900
5:163441076:AG:A	acceptor_gain	0.9900
5:163441077:GG:G	acceptor_gain	0.9900
5:163441077:GGT:G	acceptor_gain	0.9900
5:163441077:GGTA:G	acceptor_gain	0.9900
5:163441328:AAAG:A	donor_gain	0.9900
5:163441329:AAG:A	donor_gain	0.9900
5:163441330:AG:A	donor_gain	0.9900
5:163441331:GG:G	donor_gain	0.9900

AlphaMissense

1929 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:163439411:G:C	R52T	1.000
5:163439411:G:T	R52M	1.000
5:163439412:G:C	R52S	1.000
5:163439412:G:T	R52S	1.000
5:163441221:A:C	R136S	1.000
5:163441221:A:T	R136S	1.000
5:163441224:G:A	M137I	1.000
5:163441224:G:C	M137I	1.000
5:163441224:G:T	M137I	1.000
5:163442476:T:A	W267R	1.000
5:163442476:T:C	W267R	1.000
5:163439432:T:C	L59P	0.999
5:163439449:T:C	F65L	0.999
5:163439451:C:A	F65L	0.999
5:163439451:C:G	F65L	0.999
5:163439498:A:T	D81V	0.999
5:163441114:T:C	C101R	0.999
5:163441115:G:A	C101Y	0.999
5:163441116:C:G	C101W	0.999
5:163441127:C:A	A105D	0.999
5:163441186:A:C	S125R	0.999
5:163441188:T:A	S125R	0.999
5:163441188:T:G	S125R	0.999
5:163441198:T:C	F129L	0.999
5:163441200:T:A	F129L	0.999
5:163441200:T:G	F129L	0.999
5:163441210:G:C	D133H	0.999
5:163441211:A:C	D133A	0.999
5:163441211:A:G	D133G	0.999
5:163441211:A:T	D133V	0.999

dbSNP variants (sampled 300 via entrez): RS1000057593 (5:163449622 A>G), RS1000128828 (5:163450799 C>T), RS1000146521 (5:163450789 C>A,T), RS1000162278 (5:163457244 G>A), RS1000278532 (5:163456773 T>A,C), RS1000408692 (5:163449282 A>G), RS1000518526 (5:163451124 G>C), RS1000804448 (5:163437840 C>G), RS1000831672 (5:163442534 A>G), RS1000945737 (5:163445448 T>C), RS1000975358 (5:163445060 T>C), RS1001041779 (5:163452266 A>G), RS1001124539 (5:163442730 T>C,G), RS1001235520 (5:163437712 C>G,T), RS1001318065 (5:163450157 A>G)

Disease associations

OMIM: gene MIM:601578 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003123_15	Severe influenza A (H1N1) infection	2.000000e-13
GCST008369_17	Plasma anti-thyroglobulin levels	7.000000e-07
GCST009417_7	HIV progression (CD4 and viral load)	2.000000e-06
GCST009698_130	Metabolite levels	9.000000e-09
GCST012746_1	Aortic vascular smooth muscle cell proliferation in response to IL-1 beta	3.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0008336	disease progression measurement
EFO:0010105	CD4-positive T-lymphocyte count
EFO:0010125	viral load

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	affects response to substance, decreases expression, increases expression, increases reaction	6
Air Pollutants	increases abundance, increases oxidation, affects expression, decreases expression, affects cotreatment	4
Ozone	increases abundance, affects expression, affects cotreatment, increases oxidation, increases expression	4
sodium arsenite	increases expression, affects cotreatment, increases abundance	3
bisphenol A	affects cotreatment, decreases expression, affects expression	2
ochratoxin A	affects cotreatment, decreases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation, increases expression	2
Acrolein	increases expression, increases abundance, affects cotreatment, increases oxidation	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Estradiol	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
bufotalin	increases expression	1
naringenin	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
pyrithione zinc	decreases expression	1
trichostatin A	affects expression	1
cobaltous chloride	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases expression, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
polyhexamethyleneguanidine	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SH41	HAP1 CCNG1 (-) 1	Cancer cell line	Male
CVCL_SH42	HAP1 CCNG1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome