ELOVL4

ELOVL4
Identifiers
Aliases	ELOVL4 , ADMD, CT118, ISQMR, SCA34, STGD2, STGD3, ELOVL fatty acid elongase 4
External IDs	OMIM: 605512; MGI: 1933331; HomoloGene: 41488; GeneCards: ELOVL4; OMA:ELOVL4 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q14.1 Start 79,914,814 bp [1] End 79,947,553 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 E2 Start 83,660,745 bp [2] End 83,688,330 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of thigh skin of arm vulva thymus cerebellar vermis human penis skin of abdomen secondary oocyte postcentral gyrus orbitofrontal cortex Top expressed in skin of external ear lip skin of back skin of abdomen neural layer of retina esophagus retinal pigment epithelium umbilical cord pontine nuclei anterior horn of spinal cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity G protein-coupled photoreceptor activity protein binding 3-oxo-arachidoyl-CoA synthase activity 3-oxo-cerotoyl-CoA synthase activity 3-oxo-lignoceronyl-CoA synthase activity fatty acid elongase activity very-long-chain 3-ketoacyl-CoA synthase activity Cellular component integral component of membrane integral component of endoplasmic reticulum membrane endoplasmic reticulum membrane endoplasmic reticulum membrane Biological process fatty acid biosynthetic process fatty acid metabolic process lipid metabolism fatty acid elongation, saturated fatty acid very long-chain fatty acid biosynthetic process detection of visible light sphingolipid biosynthetic process fatty acid elongation, monounsaturated fatty acid fatty acid elongation, polyunsaturated fatty acid unsaturated fatty acid biosynthetic process long-chain fatty-acyl-CoA biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6785 83603 Ensembl ENSG00000118402 ENSMUSG00000032262 UniProt Q9GZR5 Q9EQC4 RefSeq (mRNA) NM_022726 NM_148941 RefSeq (protein) NP_073563 NP_683743 Location (UCSC) Chr 6: 79.91 – 79.95 Mb Chr 9: 83.66 – 83.69 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Elongation of very long chain fatty acids protein 4 is a protein that in humans is encoded by the ELOVL4 gene. ^{[5] [6]}

ELOVL4 is a member of a large family of fatty acid elongases (ELO) that catalyzes the rate-limiting step in the elongation of long chain fatty acids (LC-FA) into very long-chain saturated (VLC-SFA) and polyunsaturated (VLC-PUFA) fatty acids, collectively known as VLC-FA (very long chain fatty acid). ^{[7] [8]} ELOVL4 and its products are found in the brain, skin, retina, meibomian glands, testes and sperm. ^{[9] [10] [11] [12] [13] [14] [15]} Known mutations of ELOVL4 in humans cause diseases such as Autosomal Dominant Stargardt-like Macular Dystrophy (STGD3), spinocerebellar ataxia-34 (SCA34), skin deformities and seizures. ^{[16] [17] [18] [19] [20] [21] [22] [23] [24] [25]}

See also

• Stargardt disease

References

1. GRCh38: Ensembl release 89: ENSG00000118402 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032262 – 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. Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ, Austin CP, Gould RJ, Ayyagari R, Petrukhin K (Jan 2001). "A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy". Nature Genetics. 27 (1): 89–93. doi:10.1038/83817. PMID   11138005. S2CID   23672516.
6. "Entrez Gene: ELOVL4 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 4".
7. Agbaga MP, Brush RS, Mandal MN, Henry K, Elliott MH, Anderson RE (2008-09-02). "Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids". Proceedings of the National Academy of Sciences of the United States of America. 105 (35): 12843–12848. Bibcode:2008PNAS..10512843A. doi: 10.1073/pnas.0802607105 . ISSN   1091-6490. PMC   2525561 . PMID   18728184.
8. Vasireddy V, Uchida Y, Salem N, Kim SY, Mandal MN, Reddy GB, Bodepudi R, Alderson NL, Brown JC, Hama H, Dlugosz A (2007-03-01). "Loss of functional ELOVL4 depletes very long-chain fatty acids (> or =C28) and the unique omega-O-acylceramides in skin leading to neonatal death". Human Molecular Genetics. 16 (5): 471–482. doi:10.1093/hmg/ddl480. ISSN   0964-6906. PMC   1839956 . PMID   17208947.
9. Yeboah GK, Lobanova ES, Brush RS, Agbaga MP (2021). "Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4". Journal of Lipid Research. 62: 100030. doi: 10.1016/j.jlr.2021.100030 . ISSN   0022-2275. PMC   8042400 . PMID   33556440.
10. Bennett LD, Brush RS, Chan M, Lydic TA, Reese K, Reid GE, Busik JV, Elliott MH, Anderson RE (2014-04-10). "Effect of reduced retinal VLC-PUFA on rod and cone photoreceptors". Investigative Ophthalmology & Visual Science. 55 (5): 3150–3157. doi:10.1167/iovs.14-13995. ISSN   1552-5783. PMC   4027810 . PMID   24722693.
11. Craig LB, Brush RS, Sullivan MT, Zavy MT, Agbaga MP, Anderson RE (July 2019). "Decreased very long chain polyunsaturated fatty acids in sperm correlates with sperm quantity and quality". Journal of Assisted Reproduction and Genetics. 36 (7): 1379–1385. doi:10.1007/s10815-019-01464-3. ISSN   1573-7330. PMC   6642247 . PMID   31073727.
12. Vasireddy V, Uchida Y, Salem N, Kim SY, Mandal MN, Reddy GB, Bodepudi R, Alderson NL, Brown JC, Hama H, Dlugosz A (2007-03-01). "Loss of functional ELOVL4 depletes very long-chain fatty acids (> or =C28) and the unique omega-O-acylceramides in skin leading to neonatal death". Human Molecular Genetics. 16 (5): 471–482. doi:10.1093/hmg/ddl480. ISSN   0964-6906. PMC   1839956 . PMID   17208947.
13. Butovich IA (March 2009). "Cholesteryl esters as a depot for very long chain fatty acids in human meibum". Journal of Lipid Research. 50 (3): 501–513. doi: 10.1194/jlr.M800426-JLR200 . ISSN   0022-2275. PMC   2638107 . PMID   18836212.
14. McMahon A, Lu H, Butovich IA (2014-05-01). "A role for ELOVL4 in the mouse meibomian gland and sebocyte cell biology". Investigative Ophthalmology & Visual Science. 55 (5): 2832–2840. doi:10.1167/iovs.13-13335. ISSN   1552-5783. PMC   4008046 . PMID   24677106.
15. Hopiavuori BR, Deák F, Wilkerson JL, Brush RS, Rocha-Hopiavuori NA, Hopiavuori AR, Ozan KG, Sullivan MT, Wren JD, Georgescu C, Szweda L (February 2018). "Homozygous Expression of Mutant ELOVL4 Leads to Seizures and Death in a Novel Animal Model of Very Long-Chain Fatty Acid Deficiency". Molecular Neurobiology. 55 (2): 1795–1813. doi:10.1007/s12035-017-0824-8. ISSN   1559-1182. PMC   5820379 . PMID   29168048.
16. Yeboah GK, Lobanova ES, Brush RS, Agbaga MP (2021). "Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4". Journal of Lipid Research. 62: 100030. doi: 10.1016/j.jlr.2021.100030 . ISSN   1539-7262. PMC   8042400 . PMID   33556440.
17. Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE (January 2001). "A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy". Nature Genetics. 27 (1): 89–93. doi:10.1038/83817. ISSN   1061-4036. PMID   11138005. S2CID   23672516.
18. Bernstein PS, Tammur J, Singh N, Hutchinson A, Dixon M, Pappas CM, Zabriskie NA, Zhang K, Petrukhin K, Leppert M, Allikmets R (December 2001). "Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene". Investigative Ophthalmology & Visual Science. 42 (13): 3331–3336. ISSN   0146-0404. PMID   11726641.
19. Maugeri A, Meire F, Hoyng CB, Vink C, Van Regemorter N, Karan G, Yang Z, Cremers FP, Zhang K (December 2004). "A novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like macular dystrophy". Investigative Ophthalmology & Visual Science. 45 (12): 4263–4267. doi: 10.1167/iovs.04-0078 . ISSN   0146-0404. PMID   15557430.
20. Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M, Drouin CA, Rouleau GA, Nguyen DK, Cossette P (April 2014). "Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia". JAMA Neurology. 71 (4): 470–475. doi:10.1001/jamaneurol.2013.6337. ISSN   2168-6157. PMID   24566826.
21. Ozaki K, Doi H, Mitsui J, Sato N, Iikuni Y, Majima T, Yamane K, Irioka T, Ishiura H, Doi K, Morishita S (July 2015). "A Novel Mutation in ELOVL4 Leading to Spinocerebellar Ataxia (SCA) With the Hot Cross Bun Sign but Lacking Erythrokeratodermia: A Broadened Spectrum of SCA34". JAMA Neurology. 72 (7): 797–805. doi: 10.1001/jamaneurol.2015.0610 . ISSN   2168-6157. PMID   26010696. S2CID   6416150.
22. Bourassa CV, Raskin S, Serafini S, Teive HA, Dion PA, Rouleau GA (August 2015). "A New ELOVL4 Mutation in a Case of Spinocerebellar Ataxia With Erythrokeratodermia". JAMA Neurology. 72 (8): 942–943. doi:10.1001/jamaneurol.2015.0888. ISSN   2168-6157. PMID   26258735.
23. Bourque PR, Warman-Chardon J, Lelli DA, LaBerge L, Kirshen C, Bradshaw SH, Hartley T, Boycott KM (August 2018). "Novel ELOVL4 mutation associated with erythrokeratodermia and spinocerebellar ataxia (SCA 34)". Neurology. Genetics. 4 (4): e263. doi:10.1212/NXG.0000000000000263. ISSN   2376-7839. PMC   6066365 . PMID   30065956.
24. Xiao C, Binkley EM, Rexach J, Knight-Johnson A, Khemani P, Fogel BL, Das S, Stone EM, Gomez CM (October 2019). "A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an ELOVL4 mutation". Neurology. Genetics. 5 (5): e357. doi:10.1212/NXG.0000000000000357. ISSN   2376-7839. PMC   6812731 . PMID   31750392.
25. Beaudin M, Sellami L, Martel C, Touzel-Deschênes L, Houle G, Martineau L, Lacroix K, Lavallée A, Chrestian N, Rouleau GA, Gros-Louis F (April 2020). "Characterization of the phenotype with cognitive impairment and protein mislocalization in SCA34". Neurology. Genetics. 6 (2): e403. doi:10.1212/NXG.0000000000000403. ISSN   2376-7839. PMC   7073455 . PMID   32211516.

Further reading

• Zhang K, Bither PP, Park R, Donoso LA, Seidman JG, Seidman CE (1994). "A dominant Stargardt's macular dystrophy locus maps to chromosome 13q34". Archives of Ophthalmology. 112 (6): 759–64. doi:10.1001/archopht.1994.01090180057035. PMID   8002833. S2CID   23396964.
• Stone EM, Nichols BE, Kimura AE, Weingeist TA, Drack A, Sheffield VC (1994). "Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q". Archives of Ophthalmology. 112 (6): 765–72. doi:10.1001/archopht.1994.01090180063036. PMID   8002834.
• Edwards AO, Miedziak A, Vrabec T, Verhoeven J, Acott TS, Weleber RG, Donoso LA (1999). "Autosomal dominant Stargardt-like macular dystrophy: I. Clinical characterization, longitudinal follow-up, and evidence for a common ancestry in families linked to chromosome 6q14". American Journal of Ophthalmology. 127 (4): 426–35. doi:10.1016/S0002-9394(98)00331-6. PMID   10218695.
• Li Y, Marcos I, Borrego S, Yu Z, Zhang K, Antiñolo G (2001). "Evaluation of the ELOVL4 gene in families with retinitis pigmentosa linked to the RP25 locus". Journal of Medical Genetics. 38 (7): 478–80. doi:10.1136/jmg.38.7.478. PMC   1757187 . PMID   11474659.
• Edwards AO, Donoso LA, Ritter R (2001). "A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family". Investigative Ophthalmology & Visual Science. 42 (11): 2652–63. PMID   11581213.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Rivolta C, Ayyagari R, Sieving PA, Berson EL, Dryja TP (2003). "Evaluation of the ELOVL4 gene in patients with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis". Molecular Vision. 9: 49–51. PMID   12592226.
• Lagali PS, Liu J, Ambasudhan R, Kakuk LE, Bernstein SL, Seigel GM, Wong PW, Ayyagari R (2003). "Evolutionarily conserved ELOVL4 gene expression in the vertebrate retina". Investigative Ophthalmology & Visual Science. 44 (7): 2841–50. doi: 10.1167/iovs.02-0991 . PMID   12824221.
• Vrabec TR, Tantri A, Edwards A, Frost A, Donoso LA (2003). "Autosomal dominant Stargardt-like macular dystrophy: identification of a new family with a mutation in the ELOVL4 gene". American Journal of Ophthalmology. 136 (3): 542–5. doi:10.1016/S0002-9394(03)00227-7. PMID   12967813.
• Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. Bibcode:2003Natur.425..805M. doi: 10.1038/nature02055 . PMID   14574404.
• Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Ambasudhan R, Wang X, Jablonski MM, Thompson DA, Lagali PS, Wong PW, Sieving PA, Ayyagari R (2004). "Atrophic macular degeneration mutations in ELOVL4 result in the intracellular misrouting of the protein". Genomics. 83 (4): 615–25. doi:10.1016/j.ygeno.2003.10.004. PMID   15028284.
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Grayson C, Molday RS (2005). "Dominant negative mechanism underlies autosomal dominant Stargardt-like macular dystrophy linked to mutations in ELOVL4". Journal of Biological Chemistry. 280 (37): 32521–30. doi: 10.1074/jbc.M503411200 . PMID   16036915.
• Lai Z, Zhang XN, Zhou W, Yu R, Le YP (2006). "Evaluation of the ELOVL4 gene in a Chinese family with autosomal dominant STGD3-like macular dystrophy". Journal of Cellular and Molecular Medicine. 9 (4): 961–5. doi: 10.1111/j.1582-4934.2005.tb00392.x . PMC   6740257 . PMID   16364203.
• Hubbard AF, Askew EW, Singh N, Leppert M, Bernstein PS (2006). "Association of adipose and red blood cell lipids with severity of dominant Stargardt macular dystrophy (STGD3) secondary to an ELOVL4 mutation". Archives of Ophthalmology. 124 (2): 257–63. doi: 10.1001/archopht.124.2.257 . PMID   16476896.
• Seitsonen S, Lemmelä S, Holopainen J, Tommila P, Ranta P, Kotamies A, Moilanen J, Palosaari T, Kaarniranta K (2006). "Analysis of variants in the complement factor H, the elongation of very long chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular degeneration in the Finnish population". Molecular Vision. 12: 796–801. PMID   16885922.
• McMahon A, Butovich IA, Mata NL, Klein M, Ritter R, Richardson J, Birch DG, Edwards AO, Kedzierski W (2007). "Retinal pathology and skin barrier defect in mice carrying a Stargardt disease-3 mutation in elongase of very long chain fatty acids-4". Molecular Vision. 13: 258–72. PMC   2633486 . PMID   17356513.