CHAMP1

CHAMP1
Identifiers
Aliases	CHAMP1 , C13orf8, CAMP, CHAMP, ZNF828, MRD40, chromosome alignment maintaining phosphoprotein 1
External IDs	OMIM: 616327; MGI: 1196398; HomoloGene: 18780; GeneCards: CHAMP1; OMA:CHAMP1 - orthologs
Gene location (Human) Chr. Chromosome 13 (human) [1] Band 13q34 Start 114,314,482 bp [1] End 114,337,626 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8 A1.1|8 6.4 cM Start 13,919,641 bp [2] End 13,931,639 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of ileum secondary oocyte ganglionic eminence epithelium of colon tibialis anterior muscle cardiac muscle tissue of right atrium thymus skin of thigh myocardium of left ventricle stromal cell of endometrium Top expressed in hand zygote oocyte secondary oocyte primary oocyte otolith organ utricle maxillary prominence epiblast primitive streak More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding metal ion binding nucleic acid binding Cellular component cytoplasm chromosome spindle chromosome, centromeric region cytoskeleton condensed chromosome nucleus kinetochore nucleoplasm Flemming body Biological process sister chromatid biorientation protein localization to microtubule attachment of mitotic spindle microtubules to kinetochore protein localization to kinetochore Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 283489 101994 Ensembl ENSG00000198824 ENSMUSG00000047710 UniProt Q96JM3 Q8K327 RefSeq (mRNA) NM_032436 NM_001164144 NM_001164145 NM_181854 NM_001363455 RefSeq (protein) NP_001157616 NP_001157617 NP_115812 NP_862902 NP_001350384 Location (UCSC) Chr 13: 114.31 – 114.34 Mb Chr 8: 13.92 – 13.93 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Chromosome alignment-maintaining phosphoprotein 1 (CHAMP1) also known as zinc finger protein 828 (ZNF828) is a protein that in humans is encoded by the CHAMP1 gene. ^[5] CHAMP1 is a key component of a protein complex that has a role in facilitating homology-directed repair of DNA. ^[6]

Clinical Significance

Mutations in the CHAMP1 gene are associated with a neurodevelopmental disorder characterized by intellectual disability and severe speech impairment. ^{[7] [8]} This condition, often referred to as CHAMP1-related neurodevelopmental disorder , arises from a pathogenic variant in one of the two copies of the gene. ^[9] The majority of cases result from de novo mutations, meaning they are not inherited from the parents. ^[10]

Individuals with this disorder typically present with a range of symptoms, including global developmental delay, intellectual disability, and significant speech impairment. ^{[11] [12]} Common behavioral issues include features consistent with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). ^[13] Other frequently reported conditions include feeding difficulties, vision problems, seizures, and hypotonia (low muscle tone). ^[11]

Diagnosis is confirmed through genetic testing. Management is supportive and tailored to the individual's symptoms, involving physical, occupational, and speech therapies, as well as educational support. ^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000198824 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000047710 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: C13orf8 chromosome 13 open reading frame 8".
6. Li F, Zhang T, Syed A, Elbakry A, Holmer N, Nguyen H, Mukkavalli S, Greenberg RA, D'Andrea AD (February 2025). "CHAMP1 complex directs heterochromatin assembly and promotes homology-directed DNA repair". Nat Commun. 16 (1) 1714. Bibcode:2025NatCo..16.1714L. doi:10.1038/s41467-025-56834-6. PMC   11832927 . PMID   39962076.
7. Hempel M, Cremer K, Ockeloen CW (November 2015). "De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment". Journal of Medical Genetics. 52 (11): 758–762. doi:10.1177/1545968315604395. PMC   4680190 . PMID   26359341.
8. Héron D, Tabet AC, Mignot C (October 2018). "De Novo Truncating Mutations in the Kinetore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability". The American Journal of Human Genetics. 103 (4): 603–611. doi:10.1016/j.ajhg.2018.08.011. PMC   6174321 . PMID   30196985.
9. Mattioli F, Magini P, Bedeschi MF (April 2024). "CHAMP1-related disorders: pathomechanisms triggered by different genomic alterations define distinct nosological categories". Human Genetics. 31 (21): 30836–30848. doi:10.1007/s11356-024-33168-2. PMC   11096217 . PMID   38622415.
10. Tanaka AJ, Cho MT, Millan F (December 2018). "De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features". Human Mutation. 39 (12): 1903–1915. doi:10.1002/humu.23652. PMC   6294708 . PMID   30252159.
11. Schaaf CP, Koster J, Foulds N (May 2023). "A disease conceptual model for CHAMP1-related disorder". Journal of Neurodevelopmental Disorders. 15 (1): 19. doi: 10.1186/s12941-023-00586-y . PMC   10202970 . PMID   37202758.
12. Abi Raad S, Salignat V, Auvin S (July 2023). "CHAMP1-Related Disorder: Sharing 20 Years of thorough Clinical Follow-Up and Review of the Literature". Genes. 14 (7): 7361–7374. doi: 10.3390/genes14071432 . PMC   10381650 . PMID   37489569.
13. Levy T, Le Caignec C, Isidor B (July 2022). "CHAMP1 disorder is associated with a complex neurobehavioral phenotype including autism, ADHD, repetitive behaviors and sensory symptoms". Human Molecular Genetics. 31 (15): 2582–2594. doi:10.1093/hmg/ddac018. PMC   9288764 . PMID   35084013.

External links

• CHAMP1 UK - Charity for those affected by CHAMP1 disorders.
• CHAMP1 Research Foundation - Non-Profit raising funds for research into CHAMP1 and CHAMP1 disorders.
• Human CAMP genome location and CAMP gene details page in the UCSC Genome Browser .
• Human CHAMP1 genome location and CHAMP1 gene details page in the UCSC Genome Browser .

Further reading

• Yan H, Wang Y, Wang J (January 2023). "Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene". Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 40 (1): 58–61. doi: 10.1186/s40001-022-00978-4 . PMC   9827673 . PMID   36624515.
• Wang MM, Peng J, Zhou Y, He XY, Cao B (October 2020). "Autosomal dominant intellectual disability-40 caused by a de novo mutation of the CHAMP1 gene: a case report". Zhongguo Dang Dai Er Ke Za Zhi. 22 (10): 1081–1084. doi: 10.1186/s13195-020-00686-3 . PMC   7572235 . PMID   33066807.
• Itoh G, Kaji M, Kito K, Kabe Y, Hata A, Kiyono T (January 2011). "CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment". The EMBO Journal. 30 (1): 130–44. doi:10.1038/emboj.2010.286. PMC   3018590 . PMID   21081896.
• Li F, Zhang T, Syed A, Elbakry A, Holmer N, Nguyen H, Mukkavalli S, Greenberg RA, D'Andrea AD (September 2022). "CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair". Cell Reports. 40 (10) 111297. doi:10.1016/j.celrep.2022.111297. PMC   9481717 . PMID   36070669.
• Ben-Haim R, Zehavi Y, Yilmaz R, Sagi-Dain L, Ben-Zeev B, Tzadok M (October 2019). "CHAMP1 Mutations cause Refractory Infantile Myoclonic Epilepsy". Journal of Pediatric Neurology. 17 (4): 153–157. doi: 10.1055/s-0039-1693158 .
• Fujita H, Fukuda T, Hori M, Nakagawa K (May 2022). "CHAMP1-POGZ counteracts the inhibitory effect of 53BP1 on homologous recombination and affects PARP inhibitor resistance". Oncogene. 41 (19): 2706–2718. doi:10.1038/s41388-022-02299-6. PMC   9007991 . PMID   35437340.

Deciphering Developmental Disorders Study (March 2015). "Large-scale discovery of novel genetic causes of developmental disorders". Nature. 519 (7542): 223–8. Bibcode:2015Natur.519..223T. doi:10.1038/nature14135. PMC   5955210 . PMID   25533962.

• Whelan, C; Clegg, T (2020). "Language in CHAMP1 Syndrome". CHAMP1 Research Foundation.
• Clegg, T; Glaser, K (2020). "Neurodevelopmental Phenotypes in Individuals with Pathogenic Variants in CHAMP1". CHAMP1 Research Foundation.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID   16964243. S2CID   14294292.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi: 10.1073/pnas.0404720101 . PMC   514446 . PMID   15302935.
• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi: 10.1093/dnares/8.2.85 . PMID   11347906.