Map3k7cl, also known as MAP3K7-interacting protein 1 (MIP1), is a kinase gene. It is involved in various biological processes, and its dysregulation has been linked to multiple diseases [1-10]. Although its exact function and associated pathways are still being explored, its role in diseases suggests it is biologically important, and genetic models could be valuable for further study.

In a case of dermatofibrosarcoma protuberans with fibrosarcomatous transformation, a novel MAP3K7CL-ERG fusion was reported, indicating its potential role in this cancer transformation [1]. In pediatric sepsis, MAP3K7CL was downregulated and had a protective role, suggesting its involvement in immune response regulation in sepsis [2]. DNA methylation analysis in Tibetan elite alpinists showed that some differentially methylated CpGs were in the MAP3K7CL gene, indicating its possible role in response to extreme hypoxia [3]. In a canine model of dermatomyositis, a polymorphism in MAP3K7CL was associated with the disease, providing evidence for an epistatic foundation for this disease [4]. In congenital heart defects, CNVs in the MAP3K7CL locus were identified, and the gene was highly expressed in human and mouse embryo hearts, suggesting its role in heart development [5]. In heart failure, a genome-wide association analysis of all-cause HF identified MAP3K7CL as a locus linked to upstream HF risk factors [6]. In a Taiwanese population with chronic obstructive pulmonary disease, MAP3K7CL was identified as a prominent susceptibility locus [7]. In human vascular smooth muscle cells stimulated by high phosphorus, MAP3K7CL mRNA expression was lower in the high-phosphorus group, suggesting its possible role in vascular calcification [8]. In non-small cell lung cancer, MAP3K7CL was downregulated in tumor-educated leukocytes and was part of a four-gene panel with diagnostic potential [9]. In neurodegenerative diseases, MAP3K7CL was one of the mRNAs found in common among extracellular vesicles of patients with ALS, FTD, and PD [10].

In conclusion, Map3k7cl is involved in diverse biological processes and disease conditions, including cancer, sepsis, hypoxia response, muscle and heart-related diseases, and neurodegenerative diseases. The findings from various studies, though not directly from KO/CKO mouse models in the provided references, suggest its significance in understanding the molecular mechanisms underlying these diseases, potentially paving the way for future research and therapeutic strategies.

References:

1. Maloney, Nolan, Bridge, Julia A, de Abreu, Francine, Sakellariou, Stratigoula, Linos, Konstantinos. 2019. A novel MAP3K7CL-ERG fusion in a molecularly confirmed case of dermatofibrosarcoma protuberans with fibrosarcomatous transformation. In Journal of cutaneous pathology, 46, 532-537. doi:10.1111/cup.13469. https://pubmed.ncbi.nlm.nih.gov/30950098/

2. Zhang, Liuzhao, Chu, Quanwang, Jiang, Shuyue, Shao, Bo. 2025. Integration of Mendelian Randomization to explore the genetic influences of pediatric sepsis: a focus on RGL4, ATP9A, MAP3K7CL, and DDX11L2. In BMC pediatrics, 25, 66. doi:10.1186/s12887-025-05424-y. https://pubmed.ncbi.nlm.nih.gov/39871218/

3. Basang, Zhuoma, Zhang, Shixuan, Yang, La, Wang, Jiucun, Danzeng, Qiangba. 2021. Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia. In Journal of genetics and genomics = Yi chuan xue bao, 48, 928-935. doi:10.1016/j.jgg.2021.05.015. https://pubmed.ncbi.nlm.nih.gov/34531147/

4. Evans, Jacquelyn M, Noorai, Rooksana E, Tsai, Kate L, Famula, Thomas R, Clark, Leigh Anne. 2017. Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci. In PLoS genetics, 13, e1006604. doi:10.1371/journal.pgen.1006604. https://pubmed.ncbi.nlm.nih.gov/28158183/

5. Liu, Yichuan, Chang, Xiao, Glessner, Joseph, Sleiman, Patrick M A, Hakonarson, Hakon. 2019. Association of Rare Recurrent Copy Number Variants With Congenital Heart Defects Based on Next-Generation Sequencing Data From Family Trios. In Frontiers in genetics, 10, 819. doi:10.3389/fgene.2019.00819. https://pubmed.ncbi.nlm.nih.gov/31552105/

6. Aragam, Krishna G, Chaffin, Mark, Levinson, Rebecca T, Kathiresan, Sekar, Lubitz, Steven A. 2018. Phenotypic Refinement of Heart Failure in a National Biobank Facilitates Genetic Discovery. In Circulation, 139, 489-501. doi:10.1161/CIRCULATIONAHA.118.035774. https://pubmed.ncbi.nlm.nih.gov/30586722/

7. Lin, Wei-De, Liao, Wen-Ling, Chen, Wei-Cheng, Chen, Yu-Chia, Tsai, Fuu-Jen. 2024. Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population. In BMC genomics, 25, 607. doi:10.1186/s12864-024-10526-5. https://pubmed.ncbi.nlm.nih.gov/38886662/

8. Bao, Shumin, Guo, Yan, Diao, Zongli, Guo, Weikang, Liu, Wenhu. . Genome-wide identification of lncRNAs and mRNAs differentially expressed in human vascular smooth muscle cells stimulated by high phosphorus. In Renal failure, 42, 437-446. doi:10.1080/0886022X.2020.1758722. https://pubmed.ncbi.nlm.nih.gov/32401115/

9. Niu, Limin, Guo, Wei, Song, Xingguo, Song, Xianrang, Xie, Li. 2021. Tumor-educated leukocytes mRNA as a diagnostic biomarker for non-small cell lung cancer. In Thoracic cancer, 12, 737-745. doi:10.1111/1759-7714.13833. https://pubmed.ncbi.nlm.nih.gov/33474835/

10. Sproviero, Daisy, Gagliardi, Stella, Zucca, Susanna, Calogero, Raffaele A, Cereda, Cristina. 2022. Extracellular Vesicles Derived From Plasma of Patients With Neurodegenerative Disease Have Common Transcriptomic Profiling. In Frontiers in aging neuroscience, 14, 785741. doi:10.3389/fnagi.2022.785741. https://pubmed.ncbi.nlm.nih.gov/35250537/