CHTF8

Summary

CHTF8 (chromosome transmission fidelity factor 8, HGNC:24353) is a protein-coding gene on chromosome 16q22.1, encoding Chromosome transmission fidelity protein 8 homolog (P0CG13). Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. It is a selective cancer dependency (DepMap: 57.0% of cell lines).

This gene encodes a short protein that forms part of the Ctf18 replication factor C (RFC) complex that occurs in both yeast and mammals. The heteroheptameric RFC complex plays a role in sister chromatid cohesion and may load the replication clamp PCNA (proliferating cell nuclear antigen) onto DNA during DNA replication and repair. This gene is ubiquitously expressed and has been shown to have reduced expression in renal and prostate tumors. Alternatively spliced transcript variants have been described. This gene has a pseudogene on chromosome X.

Source: NCBI Gene 54921 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 23 total
• Cancer dependency (DepMap): dependent in 57.0% of screened cell lines
• MANE Select transcript: NM_001039690

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24353
Approved symbol	CHTF8
Name	chromosome transmission fidelity factor 8
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20400, CTF8
Ensembl gene	ENSG00000168802
Ensembl biotype	protein_coding
OMIM	613202
Entrez	54921

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000398235, ENST00000448552, ENST00000518041, ENST00000519534, ENST00000522091, ENST00000522497, ENST00000523421, ENST00000567763

RefSeq mRNA: 2 — MANE Select: NM_001039690 NM_001039690, NM_001040146

CCDS: CCDS42185

Canonical transcript exons

ENST00000448552 — 4 exons

Exon	Start	End
ENSE00002091863	69132484	69132588
ENSE00003546695	69118010	69120649
ENSE00003681057	69121053	69121170
ENSE00003849322	69121436	69121493

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.5794 / max 263.1907, expressed in 1820 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157891	51.5794	1820
157890	1.9919	1160

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.03	gold quality
adult mammalian kidney	UBERON:0000082	94.99	gold quality
mucosa of transverse colon	UBERON:0004991	94.92	gold quality
apex of heart	UBERON:0002098	94.61	gold quality
leukocyte	CL:0000738	94.39	gold quality
monocyte	CL:0000576	94.34	gold quality
islet of Langerhans	UBERON:0000006	94.16	gold quality
right lobe of liver	UBERON:0001114	93.96	gold quality
smooth muscle tissue	UBERON:0001135	93.72	gold quality
right lobe of thyroid gland	UBERON:0001119	93.05	gold quality
lower esophagus mucosa	UBERON:0035834	93.03	gold quality
fallopian tube	UBERON:0003889	92.97	gold quality
right uterine tube	UBERON:0001302	92.91	gold quality
pancreas	UBERON:0001264	92.87	gold quality
spleen	UBERON:0002106	92.65	gold quality
body of stomach	UBERON:0001161	92.56	gold quality
left adrenal gland	UBERON:0001234	92.51	gold quality
metanephros cortex	UBERON:0010533	92.51	gold quality
body of pancreas	UBERON:0001150	92.48	gold quality
left adrenal gland cortex	UBERON:0035825	92.42	gold quality
right testis	UBERON:0004534	92.41	gold quality
stromal cell of endometrium	CL:0002255	92.40	gold quality
prostate gland	UBERON:0002367	92.39	gold quality
right adrenal gland	UBERON:0001233	92.28	gold quality
fundus of stomach	UBERON:0001160	92.23	gold quality
lymph node	UBERON:0000029	92.18	gold quality
liver	UBERON:0002107	92.14	gold quality
right adrenal gland cortex	UBERON:0035827	92.10	gold quality
left testis	UBERON:0004533	92.05	gold quality
left lobe of thyroid gland	UBERON:0001120	92.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 57.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• 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)
• 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)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chtf8	ENSDARG00000069045
mus_musculus	Chtf8	ENSMUSG00000046691
drosophila_melanogaster	CG34001	FBGN0054001
caenorhabditis_elegans	ctf-8	WBGENE00011915

Protein

Protein identifiers

Chromosome transmission fidelity protein 8 homolog — P0CG13 (reviewed: P0CG13)

All UniProt accessions (5): P0CG13, E5RGY5, E5RHL4, H3BQB7, J3KSJ7

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, DSCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated the presence of primed DNA, replication protein A (RPA) and proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. It also interacts with and stimulates POLH, which is suggestive of a protein network that coordinates DNA repair, recombination and chromosome cohesion reactions with replication fork progression.

Subunit / interactions. Component of the CTF18-RFC complex, which consists of CTF18, CTF8, DSCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex does not interact with the Rad9/Rad1/Hus1 complex. The CTF18-RFC complex interacts with POLH. CTF18/CTF8/DSCC1 associate with PCNA. CTF8 exists as a dimer with DSCC1.

Subcellular location. Nucleus.

Similarity. Belongs to the CTF8 family.

RefSeq proteins (2): NP_001034779, NP_001035236 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018607	Ctf8	Family

Pfam: PF09696

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CG13-F1	86.99	0.61

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: 123 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, chr16q22, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_SISTER_CHROMATID_COHESION, GOBP_DNA_BIOSYNTHETIC_PROCESS, REACTOME_EXTENSION_OF_TELOMERES, GOBP_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, GOBP_DNA_REPLICATION, GOBP_MITOTIC_SISTER_CHROMATID_COHESION, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS

GO Biological Process (3): DNA replication (GO:0006260), mitotic sister chromatid cohesion (GO:0007064), positive regulation of DNA-directed DNA polymerase activity (GO:1900264)

GO Molecular Function (4): DNA binding (GO:0003677), DNA clamp loader activity (GO:0003689), protein binding (GO:0005515), single-stranded DNA helicase activity (GO:0017116)

GO Cellular Component (3): nucleoplasm (GO:0005654), Ctf18 RFC-like complex (GO:0031390), nucleus (GO:0005634)

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
DNA metabolic process	1
DNA biosynthetic process	1
sister chromatid cohesion	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
DNA binding	1
ATP-dependent activity, acting on DNA	1
binding	1
DNA helicase activity	1
nuclear lumen	1
cellular anatomical structure	1
chromosome	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHTF8	CHTF18	Q8WVB6	999
CHTF8	DSCC1	Q9BVC3	999
CHTF8	RFC2	P32846	989
CHTF8	RFC5	P40937	978
CHTF8	RFC3	P40938	970
CHTF8	SMC3	Q9UQE7	910
CHTF8	RFC4	P35249	909
CHTF8	ESCO1	Q5FWF5	878
CHTF8	WAPL	Q7Z5K2	849
CHTF8	WDHD1	O75717	838
CHTF8	PDS5A	Q29RF7	832
CHTF8	ESCO2	Q56NI9	822
CHTF8	RAD21	O60216	732
CHTF8	ATAD5	Q96QE3	723
CHTF8	RAD17	O75943	672

IntAct

27 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC4	RAD17	psi-mi:“MI:0914”(association)	0.730
CHTF8	IL36A	psi-mi:“MI:0915”(physical association)	0.670
DSCC1	CHTF8	psi-mi:“MI:0914”(association)	0.530
FKBP9	CASC3	psi-mi:“MI:0914”(association)	0.530
CHTF8	AP4M1	psi-mi:“MI:0915”(physical association)	0.370
FKBP9	COL2A1	psi-mi:“MI:0914”(association)	0.350
PPIE	PLRG1	psi-mi:“MI:0914”(association)	0.350
RFC4	RAD1	psi-mi:“MI:0914”(association)	0.350
IL36A	RNF40	psi-mi:“MI:0914”(association)	0.350
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.350
KCTD12	DUSP11	psi-mi:“MI:0914”(association)	0.350
CHTF18	ALDOB	psi-mi:“MI:0914”(association)	0.350
CPNE2	SUPT5H	psi-mi:“MI:0914”(association)	0.350
KCTD12	CYTH3	psi-mi:“MI:0914”(association)	0.350
RFC4	A2ML1	psi-mi:“MI:0914”(association)	0.350
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (48): CHTF8 (Affinity Capture-RNA), CHTF8 (Affinity Capture-RNA), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Two-hybrid), RFC3 (Affinity Capture-Western), CHTF8 (Proximity Label-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS)

ESM2 similar proteins: D3ZLY0, O08848, O35473, O95453, P0C6T1, P0CG11, P0CG13, P0CG15, P0CL18, P13984, P41214, P50747, P69341, Q01750, Q03123, Q05B58, Q13901, Q15650, Q2T9L9, Q2T9Y1, Q32PE4, Q3U2J5, Q5PPG7, Q5RA63, Q5RBU4, Q5RC51, Q5RK19, Q5U3V9, Q5ZHS3, Q6DC64, Q6GR37, Q6NYU2, Q6P4H8, Q7TSU0, Q80YV4, Q8BY71, Q8IVD9, Q8K2Q0, Q8R0A0, Q8R1T1

Diamond homologs: P0C6T1, P0CG11, P0CG13, P0CG15

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

568 predictions. Top by Δscore:

Variant	Effect	Δscore
16:69121166:TCGCA:T	acceptor_gain	1.0000
16:69121167:CGCA:C	acceptor_gain	1.0000
16:69121167:CGCAC:C	acceptor_gain	1.0000
16:69121168:GCA:G	acceptor_gain	1.0000
16:69121169:CA:C	acceptor_gain	1.0000
16:69121169:CAC:C	acceptor_gain	1.0000
16:69121170:ACTG:A	acceptor_loss	1.0000
16:69121171:C:CA	acceptor_loss	1.0000
16:69121171:C:CC	acceptor_gain	1.0000
16:69121431:CTTA:C	donor_loss	1.0000
16:69121432:TTA:T	donor_loss	1.0000
16:69121433:TA:T	donor_loss	1.0000
16:69121434:ACC:A	donor_loss	1.0000
16:69121435:C:CG	donor_loss	1.0000
16:69121489:ACAAG:A	acceptor_gain	1.0000
16:69121490:CAAG:C	acceptor_gain	1.0000
16:69121490:CAAGC:C	acceptor_gain	1.0000
16:69121491:AAG:A	acceptor_gain	1.0000
16:69121492:AG:A	acceptor_gain	1.0000
16:69121492:AGC:A	acceptor_loss	1.0000
16:69121493:GC:G	acceptor_loss	1.0000
16:69121494:C:CC	acceptor_gain	1.0000
16:69121494:C:T	acceptor_loss	1.0000
16:69121495:T:A	acceptor_loss	1.0000
16:69120649:CCTT:C	acceptor_gain	0.9900
16:69121048:CTCA:C	donor_loss	0.9900
16:69121051:A:T	donor_loss	0.9900
16:69121052:C:CT	donor_loss	0.9900
16:69121430:ACTT:A	donor_loss	0.9900
16:69121434:A:AC	donor_gain	0.9900

AlphaMissense

774 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:69120473:G:C	F106L	0.996
16:69120473:G:T	F106L	0.996
16:69120474:A:G	F106S	0.996
16:69120475:A:G	F106L	0.996
16:69120609:C:T	G61E	0.996
16:69120610:C:A	G61W	0.996
16:69120576:A:T	V72D	0.995
16:69120609:C:A	G61V	0.995
16:69120463:G:A	P110S	0.994
16:69120462:G:T	P110H	0.993
16:69120499:C:G	A98P	0.993
16:69120627:C:T	G55E	0.993
16:69120636:A:G	L52P	0.993
16:69120615:A:G	L59P	0.992
16:69120627:C:A	G55V	0.992
16:69121124:C:G	G24R	0.992
16:69121124:C:T	G24R	0.992
16:69120475:A:C	F106V	0.991
16:69120475:A:T	F106I	0.991
16:69120579:G:T	A71E	0.991
16:69121075:C:T	G40E	0.991
16:69120463:G:T	P110T	0.990
16:69120466:G:T	R109S	0.989
16:69120482:C:A	K103N	0.988
16:69120482:C:G	K103N	0.988
16:69121129:A:G	L22P	0.988
16:69121076:C:G	G40R	0.987
16:69121076:C:T	G40R	0.987
16:69121123:C:T	G24E	0.987
16:69120610:C:G	G61R	0.986

dbSNP variants (sampled 300 via entrez): RS1000311617 (16:69119977 G>A,C), RS1000537458 (16:69130925 T>C), RS1000769290 (16:69130528 C>A), RS1000915406 (16:69134408 G>C), RS1001210112 (16:69122032 C>A,T), RS1001282816 (16:69125686 A>C,G), RS1001868649 (16:69125805 G>A,C), RS1001898988 (16:69131595 C>A,G), RS1002171595 (16:69129710 TCTC>T), RS1002359386 (16:69126055 A>G), RS1002374308 (16:69131869 A>T), RS1002433966 (16:69117915 G>A), RS1002568418 (16:69134182 G>A), RS1002621283 (16:69120871 T>C), RS1002887875 (16:69118625 T>C)

Disease associations

OMIM: gene MIM:613202 | 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
GCST005951_13	Body mass index	5.000000e-11
GCST010703_183	Brain morphology (MOSTest)	5.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
GSK-J4	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Nickel	decreases expression	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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