The role of HCFC1 in syndromic and non-syndromic intellectual disability
Main Article Content
Abstract
Mutations in the HCFC1 gene are associated with cases of syndromic (cblX) and non-syndromic intellectual disability. Syndromic individuals present with severe neurological defects including intractable epilepsy, facial dysmorphia, and intellectual disability. Non-syndromic individuals have also been described and implicate a role for HCFC1 during brain development. The penetrance of phenotypes and the presence of an overall syndrome is associated with the location of the mutation within the HCFC1 protein. Thus, one could hypothesize that the positioning of HCFC1 mutations lead to different neurological phenotypes that include but are not restricted to intellectual disability. The HCFC1 protein is comprised of multiple domains that function in cellular proliferation/metabolism. Several reports of HCFC1 disease variants have been identified, but a comprehensive review of each variant and its associated phenotypes has not yet been compiled. Here we perform a detailed review of HCFC1 function, model systems, variant location, and accompanying phenotypes to highlight current knowledge and the future status of the field.
Keywords:
cblX, intellectual disability, HCFC1, functional analysis
Article Details
How to Cite
CASTRO, Victoria L.; QUINTANA, Anita M..
The role of HCFC1 in syndromic and non-syndromic intellectual disability.
Medical Research Archives, [S.l.], v. 8, n. 6, june 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2122>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v8i6.2122.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Watkins D, Rosenblatt DS. Inborn errors of cobalamin absorption and metabolism. Am J Med Genet C Semin Med Genet. 2011;157C(1):33-44. doi:10.1002/ajmg.c.30288
2. Kim J, Gherasim C, Banerjee R. Decyanation of vitamin B12 by a trafficking chaperone. Proc Natl Acad Sci U S A. 2008;105(38):14551-14554. doi:10.1073/pnas.0805989105
3. Froese DS, Krojer T, Wu X, et al. Structure of MMACHC reveals an arginine-rich pocket and a domain-swapped dimer for its B12 processing function. Biochemistry. 2012;51(25):5083-5090. doi:10.1021/bi300150y
4. Hannibal L, Kim J, Brasch NE, et al. Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Mol Genet Metab. 2009;97(4):260-266. doi:10.1016/j.ymgme.2009.04.005
5. Froese DS, Kopec J, Fitzpatrick F, et al. Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking. J Biol Chem. 2015;290(49):29167-29177. doi:10.1074/jbc.M115.683268
6. Orphanet: Methylmalonic acidemia with homocystinuria, type cblC. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=79282. Accessed May 9, 2016.
7. Coelho D, Suormala T, Stucki M, et al. Gene identification for the cblD defect of vitamin B12 metabolism. N Engl J Med. 2008;358(14):1454-1464. doi:10.1056/NEJMoa072200
8. Dobson CM, Wai T, Leclerc D, et al. Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. Proc Natl Acad Sci U S A. 2002;99(24):15554-15559. doi:10.1073/pnas.242614799
9. Dobson CM, Wai T, Leclerc D, et al. Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. Hum Mol Genet. 2002;11(26):3361-3369.
10. Yu H-C, Sloan JL, Scharer G, et al. An X-Linked Cobalamin Disorder Caused by Mutations in Transcriptional Coregulator HCFC1. Am J Hum Genet. 2013;93(3):506-514. doi:10.1016/j.ajhg.2013.07.022
11. Michaud J, Praz V, Faresse NJ, et al. HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy. Genome Res. April 2013. doi:10.1101/gr.150078.112
12. Huang L, Jolly LA, Willis-Owen S, et al. A Noncoding, Regulatory Mutation Implicates HCFC1 in Nonsyndromic Intellectual Disability. Am J Hum Genet. 2012;91(4):694-702. doi:10.1016/j.ajhg.2012.08.011
13. Jolly LA, Nguyen LS, Domingo D, et al. HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain. Hum Mol Genet. 2015;24(12):3335-3347. doi:10.1093/hmg/ddv083
14. Koufaris C, Alexandrou A, Tanteles GA, Anastasiadou V, Sismani C. A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder. Biomed Rep. 2016;4(2):215-218. doi:10.3892/br.2015.559
15. Gérard M, Morin G, Bourillon A, et al. Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder. Eur J Med Genet. 2015;58(3):148-153. doi:10.1016/j.ejmg.2014.12.015
16. X-Linked Cobalamin Disorder (HCFC1) Mimicking Nonketotic Hyperglycinemia With Increased Both Cerebrospinal Fluid Glycine and Methylmalonic Acid. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/28363510. Accessed January 27, 2020.
17. Dejosez M, Levine SS, Frampton GM, et al. Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev. 2010;24(14):1479-1484. doi:10.1101/gad.1935210
18. Dejosez M, Levine SS, Frampton GM, et al. Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev. 2010;24(14):1479-1484. doi:10.1101/gad.1935210
19. Mazars R, Gonzalez-de-Peredo A, Cayrol C, et al. The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias. J Biol Chem. 2010;285(18):13364-13371. doi:10.1074/jbc.M109.072579
20. Quintana AM, Yu H-C, Brebner A, et al. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities. Hum Mol Genet. 2017;26(15):2838-2849. doi:10.1093/hmg/ddx157
21. Pupavac M, Watkins D, Petrella F, et al. Inborn Error of Cobalamin Metabolism Associated with the Intracellular Accumulation of Transcobalamin-Bound Cobalamin and Mutations in ZNF143, Which Codes for a Transcriptional Activator. Hum Mutat. 2016;37(9):976-982. doi:10.1002/humu.23037
22. Piton A, Gauthier J, Hamdan FF, et al. Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol Psychiatry. 2011;16(8):867-880. doi:10.1038/mp.2010.54
23. Tarpey PS, Smith R, Pleasance E, et al. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet. 2009;41(5):535-543. doi:10.1038/ng.367
24. Daou S, Mashtalir N, Hammond-Martel I, et al. Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the host cell factor-1 maturation pathway. Proc Natl Acad Sci U S A. 2011;108(7):2747-2752. doi:10.1073/pnas.1013822108
25. Capotosti F, Guernier S, Lammers F, et al. O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1. Cell. 2011;144(3):376-388. doi:10.1016/j.cell.2010.12.030
26. Luciano RL, Wilson AC. An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP. Proc Natl Acad Sci U S A. 2002;99(21):13403-13408. doi:10.1073/pnas.202200399
27. Bhuiyan T, Waridel P, Kapuria V, Zoete V, Herr W. Distinct OGT-Binding Sites Promote HCF-1 Cleavage. PloS One. 2015;10(8):e0136636. doi:10.1371/journal.pone.0136636
28. Julien E, Herr W. Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF-1. EMBO J. 2003;22(10):2360-2369. doi:10.1093/emboj/cdg242
29. Wilson AC, Boutros M, Johnson KM, Herr W. HCF-1 amino- and carboxy-terminal subunit association through two separate sets of interaction modules: involvement of fibronectin type 3 repeats. Mol Cell Biol. 2000;20(18):6721-6730. doi:10.1128/mcb.20.18.6721-6730.2000
30. Tyagi S, Chabes AL, Wysocka J, Herr W. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol Cell. 2007;27(1):107-119. doi:10.1016/j.molcel.2007.05.030
31. Wilson AC, Parrish JE, Massa HF, Nelson DL, Trask BJ, Herr W. The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney. Genomics. 1995;25(2):462-468. doi:10.1016/0888-7543(95)80046-o
32. Wilson AC, Freiman RN, Goto H, Nishimoto T, Herr W. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression. Mol Cell Biol. 1997;17(10):6139-6146.
33. Zhou P, Wang Z, Yuan X, et al. Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with host cell factor-1 (HCF-1). J Biol Chem. 2013;288(24):17532-17543. doi:10.1074/jbc.M112.439729
34. Yokoyama A, Wang Z, Wysocka J, et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol. 2004;24(13):5639-5649. doi:10.1128/MCB.24.13.5639-5649.2004
35. Misaghi S, Ottosen S, Izrael-Tomasevic A, et al. Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1. Mol Cell Biol. 2009;29(8):2181-2192. doi:10.1128/MCB.01517-08
36. Machida YJ, Machida Y, Vashisht AA, Wohlschlegel JA, Dutta A. The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J Biol Chem. 2009;284(49):34179-34188. doi:10.1074/jbc.M109.046755
37. Yu H, Mashtalir N, Daou S, et al. The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Mol Cell Biol. 2010;30(21):5071-5085. doi:10.1128/MCB.00396-10
38. Tyagi S, Herr W. E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases. EMBO J. 2009;28(20):3185-3195. doi:10.1038/emboj.2009.258
39. Minocha S, Sung T-L, Villeneuve D, Lammers F, Herr W. Compensatory embryonic response to allele-specific inactivation of the murine X-linked gene Hcfc1. Dev Biol. 2016;412(1):1–17. doi:10.1016/j.ydbio.2016.02.019
40. Minocha S, Bessonnard S, Sung T-L, Moret C, Constam DB, Herr W. Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification. Dev Biol. 2016;418(1):75-88. doi:10.1016/j.ydbio.2016.08.008
41. Minocha S, Herr W. Cortical and Commissural Defects Upon HCF‐1 Loss in Nkx2.1‐Derived Embryonic Neurons and Glia. Developmental Neurobiology. doi:10.1002/dneu.22704
42. Minocha S, Villeneuve D, Praz V, et al. Rapid Recapitulation of Nonalcoholic Steatohepatitis upon Loss of Host Cell Factor 1 Function in Mouse Hepatocytes. Mol Cell Biol. 2019;39(5). doi:10.1128/MCB.00405-18
43. Quintana AM. The necessity for in vivo functional analysis in human medical genetics. Med Res Arch. 2015;2(8). doi:10.18103/mra.v2i8.393
44. Quintana AM, Geiger EA, Achilly N, et al. Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression. Dev Biol. 2014;396(1):94-106. doi:10.1016/j.ydbio.2014.09.026
45. Huning L, Kunkel GR. Two paralogous znf143 genes in zebrafish encode transcriptional activator proteins with similar functions but expressed at different levels during early development. BMC Mol Cell Biol. 2020;21(1):3. doi:10.1186/s12860-020-0247-7
46. Sloan JL, Achilly NP, Arnold ML, et al. The vitamin B12 processing enzyme, mmachc, is essential for zebrafish survival, growth and retinal morphology. Hum Mol Genet. March 2020. doi:10.1093/hmg/ddaa044
47. Bergsland M, Ramsköld D, Zaouter C, Klum S, Sandberg R, Muhr J. Sequentially acting Sox transcription factors in neural lineage development. Genes Dev. 2011;25(23):2453-2464. doi:10.1101/gad.176008.111
2. Kim J, Gherasim C, Banerjee R. Decyanation of vitamin B12 by a trafficking chaperone. Proc Natl Acad Sci U S A. 2008;105(38):14551-14554. doi:10.1073/pnas.0805989105
3. Froese DS, Krojer T, Wu X, et al. Structure of MMACHC reveals an arginine-rich pocket and a domain-swapped dimer for its B12 processing function. Biochemistry. 2012;51(25):5083-5090. doi:10.1021/bi300150y
4. Hannibal L, Kim J, Brasch NE, et al. Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Mol Genet Metab. 2009;97(4):260-266. doi:10.1016/j.ymgme.2009.04.005
5. Froese DS, Kopec J, Fitzpatrick F, et al. Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking. J Biol Chem. 2015;290(49):29167-29177. doi:10.1074/jbc.M115.683268
6. Orphanet: Methylmalonic acidemia with homocystinuria, type cblC. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=79282. Accessed May 9, 2016.
7. Coelho D, Suormala T, Stucki M, et al. Gene identification for the cblD defect of vitamin B12 metabolism. N Engl J Med. 2008;358(14):1454-1464. doi:10.1056/NEJMoa072200
8. Dobson CM, Wai T, Leclerc D, et al. Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. Proc Natl Acad Sci U S A. 2002;99(24):15554-15559. doi:10.1073/pnas.242614799
9. Dobson CM, Wai T, Leclerc D, et al. Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. Hum Mol Genet. 2002;11(26):3361-3369.
10. Yu H-C, Sloan JL, Scharer G, et al. An X-Linked Cobalamin Disorder Caused by Mutations in Transcriptional Coregulator HCFC1. Am J Hum Genet. 2013;93(3):506-514. doi:10.1016/j.ajhg.2013.07.022
11. Michaud J, Praz V, Faresse NJ, et al. HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy. Genome Res. April 2013. doi:10.1101/gr.150078.112
12. Huang L, Jolly LA, Willis-Owen S, et al. A Noncoding, Regulatory Mutation Implicates HCFC1 in Nonsyndromic Intellectual Disability. Am J Hum Genet. 2012;91(4):694-702. doi:10.1016/j.ajhg.2012.08.011
13. Jolly LA, Nguyen LS, Domingo D, et al. HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain. Hum Mol Genet. 2015;24(12):3335-3347. doi:10.1093/hmg/ddv083
14. Koufaris C, Alexandrou A, Tanteles GA, Anastasiadou V, Sismani C. A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder. Biomed Rep. 2016;4(2):215-218. doi:10.3892/br.2015.559
15. Gérard M, Morin G, Bourillon A, et al. Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder. Eur J Med Genet. 2015;58(3):148-153. doi:10.1016/j.ejmg.2014.12.015
16. X-Linked Cobalamin Disorder (HCFC1) Mimicking Nonketotic Hyperglycinemia With Increased Both Cerebrospinal Fluid Glycine and Methylmalonic Acid. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/28363510. Accessed January 27, 2020.
17. Dejosez M, Levine SS, Frampton GM, et al. Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev. 2010;24(14):1479-1484. doi:10.1101/gad.1935210
18. Dejosez M, Levine SS, Frampton GM, et al. Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev. 2010;24(14):1479-1484. doi:10.1101/gad.1935210
19. Mazars R, Gonzalez-de-Peredo A, Cayrol C, et al. The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias. J Biol Chem. 2010;285(18):13364-13371. doi:10.1074/jbc.M109.072579
20. Quintana AM, Yu H-C, Brebner A, et al. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities. Hum Mol Genet. 2017;26(15):2838-2849. doi:10.1093/hmg/ddx157
21. Pupavac M, Watkins D, Petrella F, et al. Inborn Error of Cobalamin Metabolism Associated with the Intracellular Accumulation of Transcobalamin-Bound Cobalamin and Mutations in ZNF143, Which Codes for a Transcriptional Activator. Hum Mutat. 2016;37(9):976-982. doi:10.1002/humu.23037
22. Piton A, Gauthier J, Hamdan FF, et al. Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol Psychiatry. 2011;16(8):867-880. doi:10.1038/mp.2010.54
23. Tarpey PS, Smith R, Pleasance E, et al. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet. 2009;41(5):535-543. doi:10.1038/ng.367
24. Daou S, Mashtalir N, Hammond-Martel I, et al. Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the host cell factor-1 maturation pathway. Proc Natl Acad Sci U S A. 2011;108(7):2747-2752. doi:10.1073/pnas.1013822108
25. Capotosti F, Guernier S, Lammers F, et al. O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1. Cell. 2011;144(3):376-388. doi:10.1016/j.cell.2010.12.030
26. Luciano RL, Wilson AC. An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP. Proc Natl Acad Sci U S A. 2002;99(21):13403-13408. doi:10.1073/pnas.202200399
27. Bhuiyan T, Waridel P, Kapuria V, Zoete V, Herr W. Distinct OGT-Binding Sites Promote HCF-1 Cleavage. PloS One. 2015;10(8):e0136636. doi:10.1371/journal.pone.0136636
28. Julien E, Herr W. Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF-1. EMBO J. 2003;22(10):2360-2369. doi:10.1093/emboj/cdg242
29. Wilson AC, Boutros M, Johnson KM, Herr W. HCF-1 amino- and carboxy-terminal subunit association through two separate sets of interaction modules: involvement of fibronectin type 3 repeats. Mol Cell Biol. 2000;20(18):6721-6730. doi:10.1128/mcb.20.18.6721-6730.2000
30. Tyagi S, Chabes AL, Wysocka J, Herr W. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol Cell. 2007;27(1):107-119. doi:10.1016/j.molcel.2007.05.030
31. Wilson AC, Parrish JE, Massa HF, Nelson DL, Trask BJ, Herr W. The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney. Genomics. 1995;25(2):462-468. doi:10.1016/0888-7543(95)80046-o
32. Wilson AC, Freiman RN, Goto H, Nishimoto T, Herr W. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression. Mol Cell Biol. 1997;17(10):6139-6146.
33. Zhou P, Wang Z, Yuan X, et al. Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with host cell factor-1 (HCF-1). J Biol Chem. 2013;288(24):17532-17543. doi:10.1074/jbc.M112.439729
34. Yokoyama A, Wang Z, Wysocka J, et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol. 2004;24(13):5639-5649. doi:10.1128/MCB.24.13.5639-5649.2004
35. Misaghi S, Ottosen S, Izrael-Tomasevic A, et al. Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1. Mol Cell Biol. 2009;29(8):2181-2192. doi:10.1128/MCB.01517-08
36. Machida YJ, Machida Y, Vashisht AA, Wohlschlegel JA, Dutta A. The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J Biol Chem. 2009;284(49):34179-34188. doi:10.1074/jbc.M109.046755
37. Yu H, Mashtalir N, Daou S, et al. The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Mol Cell Biol. 2010;30(21):5071-5085. doi:10.1128/MCB.00396-10
38. Tyagi S, Herr W. E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases. EMBO J. 2009;28(20):3185-3195. doi:10.1038/emboj.2009.258
39. Minocha S, Sung T-L, Villeneuve D, Lammers F, Herr W. Compensatory embryonic response to allele-specific inactivation of the murine X-linked gene Hcfc1. Dev Biol. 2016;412(1):1–17. doi:10.1016/j.ydbio.2016.02.019
40. Minocha S, Bessonnard S, Sung T-L, Moret C, Constam DB, Herr W. Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification. Dev Biol. 2016;418(1):75-88. doi:10.1016/j.ydbio.2016.08.008
41. Minocha S, Herr W. Cortical and Commissural Defects Upon HCF‐1 Loss in Nkx2.1‐Derived Embryonic Neurons and Glia. Developmental Neurobiology. doi:10.1002/dneu.22704
42. Minocha S, Villeneuve D, Praz V, et al. Rapid Recapitulation of Nonalcoholic Steatohepatitis upon Loss of Host Cell Factor 1 Function in Mouse Hepatocytes. Mol Cell Biol. 2019;39(5). doi:10.1128/MCB.00405-18
43. Quintana AM. The necessity for in vivo functional analysis in human medical genetics. Med Res Arch. 2015;2(8). doi:10.18103/mra.v2i8.393
44. Quintana AM, Geiger EA, Achilly N, et al. Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression. Dev Biol. 2014;396(1):94-106. doi:10.1016/j.ydbio.2014.09.026
45. Huning L, Kunkel GR. Two paralogous znf143 genes in zebrafish encode transcriptional activator proteins with similar functions but expressed at different levels during early development. BMC Mol Cell Biol. 2020;21(1):3. doi:10.1186/s12860-020-0247-7
46. Sloan JL, Achilly NP, Arnold ML, et al. The vitamin B12 processing enzyme, mmachc, is essential for zebrafish survival, growth and retinal morphology. Hum Mol Genet. March 2020. doi:10.1093/hmg/ddaa044
47. Bergsland M, Ramsköld D, Zaouter C, Klum S, Sandberg R, Muhr J. Sequentially acting Sox transcription factors in neural lineage development. Genes Dev. 2011;25(23):2453-2464. doi:10.1101/gad.176008.111