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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CHTF18
chromosome transmission fidelity factor 18
Chromosome 16 · 16p13.3
NCBI Gene: 63922Ensembl: ENSG00000127586.18HGNC: HGNC:18435UniProt: Q8WVB6
69PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
DNA clamp loader activitysingle-stranded DNA helicase activityprotein bindingpositive regulation of DNA-directed DNA polymerase activitysensory perception of smellazoospermiapartial chromosome Y deletionspermatogenic failure 25
✦AI Summary

CHTF18 (chromosome 16 fidelity factor 18) is a component of the CTF18-RFC clamp loader complex that catalyzes ATP-dependent loading of PCNA onto primed and gapped DNA during DNA replication 1. This complex binds single-stranded and primed DNA and has weak ATPase activity stimulated by RPA and PCNA presence [UniProt]. CHTF18 plays critical roles in sister chr16 cohesion, genome stability during leading strand synthesis, and meiotic recombination 2, 3. In spermatogenesis, Chtf18-null males exhibit reduced sperm concentration and defective meiotic recombination with premature homologous chromosome 16 and delayed DNA double-strand break repair 3. Beyond its canonical replication function, CHTF18 has a moonlighting role in hematopoietic stem cell positioning and migration that is independent of its clamp loader activity 4. Disease relevance includes T lymphopenia when CHTF18 function is disrupted 4, male infertility from spermatogenic failure 5, congenital anomalies of kidney and urinary tract (CAKUT) 6, neurodevelopmental delay with epilepsy 7, and endometrial cancer through chromosome 16 8. CHTF18 variants are also associated with prostate cancer prognosis 9. These findings establish CHTF18 as a multifunctional gene critical for chr16 integrity and cell-type-specific developmental processes.

Sources cited
1
CHTF18-RFC2/5 complex regulates leading strand-specific PCNA loading and is synthetically lethal with POLE3-POLE4 loss
PMID: 41339636
2
Chtf18 null males have reduced sperm concentrations, defective meiotic recombination, premature chromosome separation, and delayed DNA double-strand break repair
PMID: 23133398
3
CHTF18 variants cause T lymphopenia through disrupted hematopoietic stem cell positioning and migration, independent of its clamp loader function
PMID: 40028343
4
CHTF18 variants identified in male infertility cohort; CHTF18 preferentially expressed in spermatogonial stem cells
PMID: 39267058
5
CHTF18 identified as candidate gene for congenital anomalies of kidney and urinary tract with biallelic variants in affected families
PMID: 37499630
6
De novo CHTF18 missense variants in AAA+ATPase domain associated with neurodevelopmental delay and epilepsy as cohesinopathy
PMID: 40717333
7
Somatic CHTF18 mutations identified in 1.9% of endometrial cancers, associated with chromosome instability
PMID: 23755103
8
CHTF18 identified as survival-related cell cycle gene in prostate cancer prognostic risk model
PMID: 35087757
Disease Associationsⓘ20
sensory perception of smellOpen Targets
0.09Suggestive
azoospermiaOpen Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.06Suggestive
spermatogenic failure 25Open Targets
0.05Suggestive
spermatogenic failure 50Open Targets
0.05Suggestive
spermatogenic failure 57Open Targets
0.05Suggestive
spermatogenic failure 54Open Targets
0.05Suggestive
spermatogenic failure 65Open Targets
0.05Suggestive
spermatogenic failure 84Open Targets
0.05Suggestive
spermatogenic failure 93Open Targets
0.05Suggestive
spermatogenic failure 63Open Targets
0.05Suggestive
spermatogenic failure 56Open Targets
0.05Suggestive
spermatogenic failure 92Open Targets
0.05Suggestive
spermatogenic failure 94Open Targets
0.05Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.05Suggestive
spermatogenic failure 48Open Targets
0.05Suggestive
spermatogenic failure 51Open Targets
0.05Suggestive
spermatogenic failure 39Open Targets
0.05Suggestive
spermatogenic failure 40Open Targets
0.05Suggestive
Isolated follicle stimulating hormone deficiencyOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LIG1Protein interaction100%PCNAProtein interaction100%POLA1Protein interaction100%POLE2Protein interaction100%PRIM2Protein interaction100%RAD17Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
33%
Lung
17%
Liver
14%
Brain
8%
Heart
4%
Gene Interaction Network
Click a node to explore
CHTF18LIG1PCNAPOLA1POLE2PRIM2RAD17
PROTEIN STRUCTURE
Preparing viewer…
PDB8UMV · 2.75 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.50 [1.31–1.71]
RankingsWhere CHTF18 stands among ~20K protein-coding genes
  • #6,789of 20,598
    Most Researched69
  • #16,156of 17,882
    Most Constrained (LOEUF)1.71
Genes detectedCHTF18
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Whole exome sequencing analysis of 167 men with primary infertility.
PMID: 39267058
BMC Med Genomics · 2024
1.00
2
Disruption of the moonlighting function of CTF18 in a patient with T-lymphopenia.
PMID: 40028343
Front Immunol · 2025
0.90
3
The genetic and biochemical basis of human leading strand synthesis.
PMID: 41339636
Nat Commun · 2025
0.80
4
Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer.
PMID: 35087757
Front Oncol · 2021
0.70
5
Sequencing of candidate chromosome instability genes in endometrial cancers reveals somatic mutations in ESCO1, CHTF18, and MRE11A.
PMID: 23755103
PLoS One · 2014
0.60