HORMAD1

HORMAD1
Identifiers
Aliases	HORMAD1 , CT46, NOHMA, HORMA domain containing 1
External IDs	OMIM: 609824; MGI: 1915231; HomoloGene: 69415; GeneCards: HORMAD1; OMA:HORMAD1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q21.3 Start 150,698,060 bp [1] End 150,720,895 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3|3 F2.1 Start 95,466,988 bp [2] End 95,494,982 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right testis left testis gonad sperm testicle monocyte granulocyte skin of hip mucosa of esophagus appendix Top expressed in spermatocyte spermatid testicle morula embryo blastocyst embryo ovarian follicle epiblast secondary oocyte More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 84072 67981 Ensembl ENSG00000143452 ENSMUSG00000028109 UniProt Q86X24 Q9D5T7 RefSeq (mRNA) NM_001199829 NM_032132 NM_001289532 NM_001289534 NM_001289537 NM_026489 NM_001373886 RefSeq (protein) NP_001186758 NP_115508 NP_001276461 NP_001276463 NP_001276466 NP_080765 NP_001360815 Location (UCSC) Chr 1: 150.7 – 150.72 Mb Chr 3: 95.47 – 95.49 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

HORMA domain-containing protein 1 (HORMAD1) also known as cancer/testis antigen 46 (CT46) is a protein that in humans is encoded by the HORMAD1 gene. ^{[5] [6] [7]}

Function

HORMAD1 is a cancer/testis antigen that plays a key role in meiotic progression. ^[6] It has shown to regulate 3 different functions during meiosis. Specifically, it:

1. Ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends
2. Promotes synaptonemal-complex formation independently of its role in homology search.
3. Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes (By similarity) ^[8]

Role in cancer

HORMAD1 has been shown to have a role in Triple-Negative Breast Cancers ^[9] and in Lung Adenocarcinomas. ^[10] In particular, the Watkins et al., paper suggested that overexpression of HORMAD1 is a driver of homologous recombination repair deficiency in these types of breast cancers, and induced widespread allelic imbalances in the genome with implications for platinum and PARP inhibitor sensitivity.

References

1. GRCh38: Ensembl release 89: ENSG00000143452 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028109 – 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. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
6. Chen YT, Venditti CA, Theiler G, Stevenson BJ, Iseli C, Gure AO, et al. (July 2005). "Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein". Cancer Immunity. 5: 9. PMID   15999985.
7. "Entrez Gene: HORMAD1 HORMA domain containing 1".
8. Shin YH, Choi Y, Erdin SU, Yatsenko SA, Kloc M, Yang F, et al. (November 2010). "Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis". PLOS Genetics. 6 (11): e1001190. doi: 10.1371/journal.pgen.1001190 . PMC   2973818 . PMID   21079677.
9. Watkins J, Weekes D, Shah V, Gazinska P, Joshi S, Sidhu B, et al. (May 2015). "Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to Homologous Recombination Deficiency in Triple-Negative Breast Cancers". Cancer Discovery. 5 (5): 488–505. doi:10.1158/2159-8290.CD-14-1092. PMC   4490184 . PMID   25770156.
10. Gao Y, Kardos J, Yang Y, Tamir TY, Mutter-Rottmayer E, Weissman B, et al. (October 2018). "The Cancer/Testes (CT) Antigen HORMAD1 promotes Homologous Recombinational DNA Repair and Radioresistance in Lung adenocarcinoma cells". Scientific Reports. 8 (1): 15304. Bibcode:2018NatSR...815304G. doi:10.1038/s41598-018-33601-w. PMC   6192992 . PMID   30333500.

Further reading

• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.
• Pangas SA, Yan W, Matzuk MM, Rajkovic A (December 2004). "Restricted germ cell expression of a gene encoding a novel mammalian HORMA domain-containing protein". Gene Expression Patterns. 5 (2): 257–63. doi:10.1016/j.modgep.2004.07.008. PMID   15567723.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC   1083732 . PMID   11256614.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.