CHTF18

Summary

CHTF18 (chromosome transmission fidelity factor 18, HGNC:18435) is a protein-coding gene on chromosome 16p13.3, encoding Chromosome transmission fidelity protein 18 homolog (Q8WVB6). Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. It is a selective cancer dependency (DepMap: 23.3% of cell lines).

This gene encodes a protein which is a component of a replication factor C (RFC) complex, which loads proliferating cell nuclear antigen (PCNA) on to DNA during the S phase of cell cycle. The encoded protein may interact with other proteins, including RFC complex 3, to form a clamp loader complex that plays a role in sister chromatid cohesion during metaphase-anaphase transition.

Source: NCBI Gene 63922 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 367 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 23.3% of screened cell lines
• MANE Select transcript: NM_022092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18435
Approved symbol	CHTF18
Name	chromosome transmission fidelity factor 18
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CHL12, C321D2.4, Ctf18
Ensembl gene	ENSG00000127586
Ensembl biotype	protein_coding
OMIM	613201
Entrez	63922

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 18 protein_coding, 6 retained_intron, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000262315, ENST00000317063, ENST00000426047, ENST00000440239, ENST00000455171, ENST00000461268, ENST00000464728, ENST00000471202, ENST00000479976, ENST00000484349, ENST00000491530, ENST00000493715, ENST00000498439, ENST00000563545, ENST00000564940, ENST00000565787, ENST00000567620, ENST00000569270, ENST00000570058, ENST00000631357, ENST00000873773, ENST00000873774, ENST00000873775, ENST00000873776, ENST00000873777, ENST00000936315, ENST00000936316, ENST00000936317, ENST00000936318, ENST00000936319, ENST00000936320, ENST00000936321, ENST00000936322

RefSeq mRNA: 1 — MANE Select: NM_022092 NM_022092

CCDS: CCDS45371

Canonical transcript exons

ENST00000262315 — 22 exons

Exon	Start	End
ENSE00000664137	791851	791948
ENSE00003472534	790347	790399
ENSE00003473534	789210	789360
ENSE00003480838	792718	792811
ENSE00003483455	788931	789125
ENSE00003512553	789547	789715
ENSE00003513699	792224	792347
ENSE00003530166	796961	797092
ENSE00003530253	797694	797751
ENSE00003543830	796717	796861
ENSE00003551417	797839	798074
ENSE00003578448	795685	795834
ENSE00003578718	794054	794201
ENSE00003582580	795132	795356
ENSE00003585496	790525	790666
ENSE00003589983	795947	796077
ENSE00003590350	792439	792590
ENSE00003606392	788620	788775
ENSE00003636490	790177	790269
ENSE00003636938	793144	793274
ENSE00003681406	792966	793064
ENSE00003787490	791161	791370

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 92.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1711 / max 352.3882, expressed in 1373 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152008	4.3600	1205
152007	1.8111	906

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	92.69	gold quality
left testis	UBERON:0004533	92.51	gold quality
mucosa of transverse colon	UBERON:0004991	90.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.52	gold quality
cerebellar hemisphere	UBERON:0002245	89.79	gold quality
cerebellar cortex	UBERON:0002129	89.64	gold quality
testis	UBERON:0000473	89.51	gold quality
pancreatic ductal cell	CL:0002079	89.32	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.15	gold quality
sural nerve	UBERON:0015488	88.76	gold quality
ventricular zone	UBERON:0003053	88.46	gold quality
cerebellum	UBERON:0002037	87.95	gold quality
ganglionic eminence	UBERON:0004023	87.84	gold quality
lower esophagus mucosa	UBERON:0035834	87.24	gold quality
granulocyte	CL:0000094	87.18	gold quality
right uterine tube	UBERON:0001302	86.79	gold quality
spleen	UBERON:0002106	85.17	gold quality
left ovary	UBERON:0002119	84.57	gold quality
right frontal lobe	UBERON:0002810	83.94	gold quality
right ovary	UBERON:0002118	83.92	gold quality
cortical plate	UBERON:0005343	83.91	gold quality
ectocervix	UBERON:0012249	83.06	gold quality
esophagus mucosa	UBERON:0002469	83.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.62	gold quality
endocervix	UBERON:0000458	82.52	gold quality
vermiform appendix	UBERON:0001154	82.39	gold quality
body of uterus	UBERON:0009853	82.33	gold quality
stromal cell of endometrium	CL:0002255	81.80	gold quality
tendon of biceps brachii	UBERON:0008188	81.79	silver quality
skin of abdomen	UBERON:0001416	81.77	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-9689	no	114.12
E-ANND-3	no	2.22

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• identification as proliferating cell nuclear antigen-binding protein (PMID:12171929)
• hCTF18, hCTF8, and hDCC1 interact with each other as well as with the p38 subunit of RFC (PMID:12766176)
• The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA. (PMID:12930902)
• Ctf18-RFC interacts physically with pol eta, which allows DNA replication forks to overcome interference by various template structures, including damaged DNA and DNA-protein complexes that maintain chromosome cohesion (PMID:17545166)
• hChlR1 has a role in the establishment of sister chromatid cohesion, with Ctf18-RFC and Fen1 (PMID:18499658)
• Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8. (PMID:20826785)
• This is the first report of somatic mutations within ESCO1 and CHTF18 in endometrial tumors and of MRE11A mutations in microsatellite-stable endometrial tumors. (PMID:23755103)
• CTF18 forms a complex with RPA when replication stress is elicited by hydroxyurea treatment or UV exposure during S phase. The interaction kinetics between CTF18 and RPA is positively associated with the phosphorylation status of Chk1. (PMID:27175616)
• Human CTF18-RFC clamp-loader complexed with non-synthesising POLE efficiently loads the PCNA sliding clamp. (PMID:28199690)
• CTF18-RFC contributes to cellular tolerance against chain-terminating nucleoside analogs (CTNAs) in cooperation with proofreading exonuclease activity of DNA polymerase epsilon. (PMID:37099849)
• The proofreading exonuclease of leading-strand DNA polymerase epsilon prevents replication fork collapse at broken template strands. (PMID:37944988)
• Cryo-EM reveals a nearly complete PCNA loading process and unique features of the human alternative clamp loader CTF18-RFC. (PMID:38669181)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chtf18	ENSDARG00000058480
mus_musculus	Chtf18	ENSMUSG00000019214
rattus_norvegicus	Chtf18	ENSRNOG00000019174
drosophila_melanogaster	cutlet	FBGN0015376
caenorhabditis_elegans		WBGENE00010676

Protein

Protein identifiers

Chromosome transmission fidelity protein 18 homolog — Q8WVB6 (reviewed: Q8WVB6)

Alternative names: CHL12

All UniProt accessions (7): Q8WVB6, A0A0D9SF58, E7EXA6, F8WCC1, H0Y7D3, H3BN43, H3BT35

UniProt curated annotations — full annotation on UniProt →

Function. Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated by the presence of primed DNA, replication protein A (RPA) and by proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. Interacts with and stimulates DNA polymerase POLH. During DNA repair synthesis, involved in loading DNA polymerase POLE at the sites of local damage.

Subunit / interactions. Component of the CTF18-RFC complex, which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. During assembly of the CTF18-RFC complex, CTF18 may first assemble into a subcomplex with RFC2, RFC3, RFC4 and RFC5. CTF18 then interacts directly with CTF8, which in turn interacts with DCC1. The CTF18-RFC complex associates with PCNA and with DNA polymerase POLH. The CTF18-RFC complex does not interact with the Rad9/Rad1/Hus1 complex. CTF18 interacts with SMC1A and RAD21. Interacts with DDX11.

Subcellular location. Nucleus.

Similarity. Belongs to the activator 1 small subunits family. CTF18 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WVB6-1	1	yes
Q8WVB6-2	2
Q8WVB6-3	3

RefSeq proteins (1): NP_071375* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR047854	RFC_lid	Domain
IPR053016	CTF18-RFC_complex	Family

Pfam: PF00004

UniProt features (72 total): helix 29, strand 17, turn 6, region of interest 5, sequence variant 5, modified residue 4, splice variant 2, compositionally biased region 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8UMV	ELECTRON MICROSCOPY	2.75
8UMY	ELECTRON MICROSCOPY	2.83
8UMW	ELECTRON MICROSCOPY	2.93
8ZWO	ELECTRON MICROSCOPY	2.99
8UN0	ELECTRON MICROSCOPY	3
8UMU	ELECTRON MICROSCOPY	3.16
9IIN	ELECTRON MICROSCOPY	3.2
9UIQ	ELECTRON MICROSCOPY	3.2
8UMT	ELECTRON MICROSCOPY	3.33
8UNJ	ELECTRON MICROSCOPY	3.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVB6-F1	64.97	0.09

Functional residue map

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

Ligand- & substrate-binding residues (1): 374–381

Post-translational modifications (4): 64, 225, 871, 51

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-174411	Polymerase switching on the C-strand of the telomere

MSigDB gene sets: 111 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, LIAO_METASTASIS, GOBP_DNA_BIOSYNTHETIC_PROCESS, AFFAR_YY1_TARGETS_DN, REACTOME_EXTENSION_OF_TELOMERES, GOBP_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, FISCHER_DREAM_TARGETS, GOBP_DNA_REPLICATION, NUYTTEN_EZH2_TARGETS_DN, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOBP_DNA_METABOLIC_PROCESS, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON

GO Biological Process (2): DNA replication (GO:0006260), positive regulation of DNA-directed DNA polymerase activity (GO:1900264)

GO Molecular Function (7): DNA binding (GO:0003677), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), DNA clamp loader activity (GO:0003689), protein binding (GO:0005515), single-stranded DNA helicase activity (GO:0017116)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), Ctf18 RFC-like complex (GO:0031390), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Telomere C-strand (Lagging Strand) Synthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	1
DNA biosynthetic process	1
DNA-directed DNA polymerase activity	1
positive regulation of catalytic activity	1
regulation of transferase activity	1
positive regulation of DNA biosynthetic process	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
DNA binding	1
ATP-dependent activity, acting on DNA	1
binding	1
DNA helicase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
chromosome	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHTF18	CHTF8	P0CG13	999
CHTF18	DSCC1	Q9BVC3	999
CHTF18	RFC2	P32846	998
CHTF18	RFC3	P40938	960
CHTF18	RFC5	P40937	949
CHTF18	ESCO1	Q5FWF5	947
CHTF18	PDS5A	Q29RF7	940
CHTF18	SMC3	Q9UQE7	940
CHTF18	RFC4	P35249	931
CHTF18	RAD17	O75943	924
CHTF18	ESCO2	Q56NI9	922
CHTF18	WAPL	Q7Z5K2	914
CHTF18	ATAD5	Q96QE3	877
CHTF18	WDHD1	O75717	846
CHTF18	RAD21	O60216	824

IntAct

75 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC4	RAD17	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DSCC1	CHTF8	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PHOSPHO1	ACY1	psi-mi:“MI:0914”(association)	0.500
CRK	CHTF18	psi-mi:“MI:0915”(physical association)	0.490
CHTF18	STAT3	psi-mi:“MI:0915”(physical association)	0.370
Phospho1	SLC4A2	psi-mi:“MI:0914”(association)	0.350
FAM83H	SEC16A	psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350

BioGRID (125): CHTF18 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS), CHTF18 (Co-fractionation), CHTF18 (Co-fractionation), CHTF18 (Affinity Capture-MS), RFC3 (Affinity Capture-Western), PCNA (Affinity Capture-Western), CHTF18 (Two-hybrid), CHTF18 (Two-hybrid), CHTF18 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6ASZ5, A0JN53, A4IG66, D3Z8X7, D3ZND0, G3X992, O00750, O08836, O70576, P0DKR2, Q15021, Q1JQC5, Q1L5Z9, Q1LWH4, Q1LXZ7, Q2YD98, Q3T1I9, Q3TV65, Q3UJU9, Q4R5Q4, Q5EAU9, Q5JTW2, Q5R6Z1, Q5TC12, Q61249, Q66H15, Q6NY52, Q6P5E6, Q6PBQ2, Q6PI26, Q80TE0, Q80V31, Q80XC6, Q8BIW9, Q8BM55, Q8K2Z4, Q8R3L2, Q8VDP4, Q8WVB6, Q92574

Diamond homologs: A0B6D7, A1KU52, A1RSA2, A1RSA3, A1RV38, A1RWU6, A1RWU7, A2BL93, A2SQR6, A2SQT3, A3CTR4, A3DNV8, A3DNV9, A3MS27, A3MS28, A4FZ74, A4FZL6, A4WGV2, A4WGV3, A4WLY0, A5UMF3, A5UMF4, A6URV8, A6US36, A6UWR5, A6VIW1, A6VJ61, A7I781, A8AC24, A9A6K6, A9A6N2, A9LZC3, B0R601, B0R7H7, B1YC69, B4RLV8, B9LPV1, C3MQ13, C3MVD2, C3N5N1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Impaired BRCA2 binding to RAD51	5	23.4×	4e-04
Activation of ATR in response to replication stress	5	22.8×	4e-04
HDR through Single Strand Annealing (SSA)	5	22.2×	4e-04
Presynaptic phase of homologous DNA pairing and strand exchange	5	20.6×	5e-04
PKR-mediated signaling	5	10.7×	6e-03
G2/M DNA damage checkpoint	5	9.1×	8e-03
Regulation of TP53 Activity through Phosphorylation	5	8.9×	9e-03
Processing of DNA double-strand break ends	5	8.7×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	294
Likely benign	24
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

3704 predictions. Top by Δscore:

Variant	Effect	Δscore
16:788721:G:GT	donor_gain	1.0000
16:788754:G:GT	donor_gain	1.0000
16:788772:G:GT	donor_gain	1.0000
16:788842:G:GT	donor_gain	1.0000
16:789124:CGG:C	donor_loss	1.0000
16:789126:G:GG	donor_gain	1.0000
16:789127:T:A	donor_loss	1.0000
16:789335:G:GT	donor_gain	1.0000
16:789545:A:AG	acceptor_gain	1.0000
16:789546:G:GG	acceptor_gain	1.0000
16:789546:GA:G	acceptor_gain	1.0000
16:789546:GAGTC:G	acceptor_gain	1.0000
16:789635:GAC:G	donor_gain	1.0000
16:789715:GGTG:G	donor_loss	1.0000
16:789716:G:GA	donor_loss	1.0000
16:789717:T:A	donor_loss	1.0000
16:790175:AG:A	acceptor_gain	1.0000
16:790176:GG:G	acceptor_gain	1.0000
16:791147:C:A	acceptor_gain	1.0000
16:791156:C:A	acceptor_gain	1.0000
16:791156:CGCAG:C	acceptor_loss	1.0000
16:791157:GCAGT:G	acceptor_loss	1.0000
16:791158:CAGTT:C	acceptor_loss	1.0000
16:791159:A:AC	acceptor_loss	1.0000
16:791159:A:AG	acceptor_gain	1.0000
16:791160:G:GC	acceptor_gain	1.0000
16:791160:GT:G	acceptor_gain	1.0000
16:791160:GTT:G	acceptor_gain	1.0000
16:791160:GTTC:G	acceptor_gain	1.0000
16:791160:GTTCA:G	acceptor_gain	1.0000

AlphaMissense

6267 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:791197:T:A	W311R	0.998
16:791197:T:C	W311R	0.998
16:790658:A:C	S296R	0.997
16:790660:T:A	S296R	0.997
16:790660:T:G	S296R	0.997
16:791185:T:A	W307R	0.997
16:791185:T:C	W307R	0.997
16:791882:G:A	G379E	0.997
16:791171:G:C	R302P	0.996
16:791177:T:C	L304P	0.996
16:791199:G:C	W311C	0.996
16:791199:G:T	W311C	0.996
16:791867:G:A	G374E	0.996
16:791894:T:C	L383P	0.996
16:792319:T:A	V433D	0.996
16:792328:A:T	E436V	0.996
16:791858:T:C	L371P	0.995
16:791888:C:T	T381I	0.995
16:791947:A:C	S401R	0.995
16:792224:T:A	S401R	0.995
16:792224:T:G	S401R	0.995
16:792312:T:C	C431R	0.995
16:792314:C:G	C431W	0.995
16:797916:T:C	F957L	0.995
16:797918:C:A	F957L	0.995
16:797918:C:G	F957L	0.995
16:790653:T:C	L294P	0.994
16:791189:T:C	L308P	0.994
16:791897:C:A	A384E	0.994
16:791923:T:G	Y393D	0.994

dbSNP variants (sampled 300 via entrez): RS1000149367 (16:792103 C>A,T), RS1000261081 (16:789879 G>A,T), RS1000336565 (16:791520 G>A), RS1000419307 (16:793793 T>C,G), RS1000473170 (16:793676 T>C), RS1000815086 (16:793037 C>G,T), RS1000942742 (16:794107 A>G,T), RS1000968959 (16:798515 C>A,G,T), RS1001498936 (16:791501 A>G), RS1001515157 (16:789743 T>C,G), RS1001691972 (16:797279 C>G,T), RS1002519499 (16:789180 C>A,G,T), RS1002628831 (16:791462 C>A,T), RS1003350822 (16:788556 A>G), RS1003490214 (16:787852 G>A,C)

Disease associations

OMIM: gene MIM:613201 | disease phenotypes: MIM:600669, MIM:617027

GenCC curated gene-disease

Mondo (2): idiopathic generalized epilepsy (MONDO:0005579), hyperaldosteronism, familial, type IV (MONDO:0014875)

Orphanet (1): Familial hyperaldosteronism type IV (Orphanet:642671)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004602_225	Mean corpuscular volume	5.000000e-14
GCST004630_174	Mean corpuscular hemoglobin	3.000000e-13
GCST005951_12	Body mass index	5.000000e-11
GCST90002390_646	Mean corpuscular hemoglobin	3.000000e-14
GCST90002392_491	Mean corpuscular volume	7.000000e-21
GCST90002396_574	Mean reticulocyte volume	6.000000e-20
GCST90002397_228	Mean spheric corpuscular volume	3.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004340	body mass index
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562694	Epilepsy, Idiopathic Generalized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465337 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	5
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
titanium dioxide	affects binding, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases sumoylation	1
Troglitazone	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Benzophenoneidum	increases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Chlorpromazine	decreases expression	1
Ivermectin	decreases expression	1
Oxygen	decreases expression	1
Plant Extracts	affects cotreatment, decreases 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
CHEMBL5338455	Binding	Binding affinity to Chtf18 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03940326	PHASE4	COMPLETED	Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT00150735	PHASE3	COMPLETED	Monotherapy With Levetiracetam in Newly Diagnosed Patients Suffering From Epilepsy
NCT00150748	PHASE3	COMPLETED	Long Term Follow up Treatment With Levetiracetam in Subjects of 4 Years and Older With Generalized Epilepsy
NCT03678753	PHASE3	COMPLETED	Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
NCT05147571	PHASE3	ACTIVE_NOT_RECRUITING	RNS System NAUTILUS Study
NCT06908356	PHASE2	RECRUITING	An Open Label Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adults With Focal Onset or Tonic-Clonic Seizures
NCT06425159	PHASE2/PHASE3	TERMINATED	A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification
NCT01311440	Not specified	COMPLETED	Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy
NCT01432821	Not specified	COMPLETED	Blinking and Yawning in Epilepsy: The Role of Dopamine
NCT03368469	Not specified	WITHDRAWN	Transcranial Direct Current Stimulation (tDCS) in Children and Adolescents With Epilepsy and Depression
NCT03457961	Not specified	UNKNOWN	Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
NCT03955432	Not specified	TERMINATED	Long-term Cardiac Monitoring in Epilepsy
NCT04252846	Not specified	COMPLETED	A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy
NCT04965571	Not specified	COMPLETED	Clinical Features and Outcome of Wilson’s Disease With Generalized Epilepsy in Chinese Patients
NCT05374928	Not specified	ACTIVE_NOT_RECRUITING	Human Epilepsy Project 3
NCT05530109	Not specified	TERMINATED	Study of Attentional Disorders in Patients Suffering From Idiopathic Generalized Epilepsy.
NCT06388174	Not specified	RECRUITING	Idiopathic Generalized Epilepsy Syndromes
NCT06797791	Not specified	COMPLETED	Assessment of Multifocal Continuous Theta Burst Transcranial Magnetic Stimulation (cTBS) Effects in Generalized Epilepsy Patients.