HOXD13

HOXD13
Identifiers
Aliases	HOXD13 , BDE, BDSD, HOX4I, SPD, SPD1, homeobox D13
External IDs	OMIM: 142989; MGI: 96205; HomoloGene: 20147; GeneCards: HOXD13; OMA:HOXD13 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2q31.1 Start 176,092,721 bp [1] End 176,095,944 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 C3|2 44.13 cM Start 74,498,654 bp [2] End 74,501,943 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in urethra vagina muscle layer of sigmoid colon ectocervix Achilles tendon seminal vesicula prostate canal of the cervix vulva rectum Top expressed in genital tubercle left colon hand tail of embryo limb bud rectum foot vas deferens urethra footplate More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific chromatin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity sequence-specific double-stranded DNA binding Cellular component nucleus Biological process pattern specification process skeletal system development regulation of branching involved in prostate gland morphogenesis male genitalia development regulation of transcription, DNA-templated limb morphogenesis embryonic digit morphogenesis embryonic hindgut morphogenesis branch elongation of an epithelium transcription, DNA-templated multicellular organism development gland morphogenesis regulation of cell population proliferation embryonic limb morphogenesis prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis anterior/posterior pattern specification morphogenesis of an epithelial fold transcription by RNA polymerase II prostate gland development response to testosterone positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3239 15433 Ensembl ENSG00000128714 ENSMUSG00000001819 UniProt P35453 P70217 RefSeq (mRNA) NM_000523 NM_008275 RefSeq (protein) NP_000514 NP_032301 Location (UCSC) Chr 2: 176.09 – 176.1 Mb Chr 2: 74.5 – 74.5 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene. ^{[5] [6] [7]} This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms.

Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9–11 genes arranged in tandem. HOXD13 is the first of several HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd13 gene plays a role in axial skeleton development and forelimb morphogenesis. ^[8]

Changes in the expression of the Hoxd13 gene in early lobe-finned fish may have also contributed to the evolution of the tetrapod limb. ^[9] Experiments investigating the impact of 5′ Hoxd overexpression in zebrafish embryos observed modified development of distal fin structures, resulting in increased proliferation, distal expansion of cartilage tissue and fin fold reduction. ^[10] A number of similar studies conducted with a range of animals, including catsharks ^[11] and marsupials, ^[12] lend further credibility to the role of the Hoxd13 gene in the fin-to-limb transition.

Clinical significance

Mutations in HOXD13 can cause several types of autosomal dominant syndactyly and brachydactyly, including brachydactyly type D ("club thumb"), brachydactyly type E, syndactyly type 5 and synpolydactyly type 1. ^[13]

See also

• Homeobox

References

1. GRCh38: Ensembl release 89: ENSG00000128714 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001819 – 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. Acampora D, D'Esposito M, Faiella A, Pannese M, Migliaccio E, Morelli F, et al. (December 1989). "The human HOX gene family". Nucleic Acids Research. 17 (24): 10385–402. doi:10.1093/nar/17.24.10385. PMC   335308 . PMID   2574852.
6. McAlpine PJ, Shows TB (July 1990). "Nomenclature for human homeobox genes". Genomics. 7 (3): 460. doi:10.1016/0888-7543(90)90186-X. PMID   1973146.
7. "Entrez Gene: HOXD13 homeobox D13".
8. Davis AP, Capecchi MR (April 1996). "A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse". Development. 122 (4): 1175–85. doi:10.1242/dev.122.4.1175. PMID   8620844.
9. Schneider I, Shubin NH (December 2012). "Making limbs from fins". Developmental Cell. 23 (6): 1121–2. doi: 10.1016/j.devcel.2012.11.011 . PMID   23237946.
10. Freitas R, Gómez-Marín C, Wilson JM, Casares F, Gómez-Skarmeta JL (December 2012). "Hoxd13 contribution to the evolution of vertebrate appendages". Developmental Cell. 23 (6): 1219–29. doi: 10.1016/j.devcel.2012.10.015 . PMID   23237954.
11. "Key genetic event underlying fin-to-limb evolution: Study of catsharks reveals how alterations in the expression, function of certain genes in limb buds underlie evolution of fish fins to limbs". ScienceDaily. Retrieved 2019-11-18.
12. Chew KY, Yu H, Pask AJ, Shaw G, Renfree MB (January 2012). "HOXA13 and HOXD13 expression during development of the syndactylous digits in the marsupial Macropus eugenii". BMC Developmental Biology. 12 (1): 2. doi: 10.1186/1471-213X-12-2 . PMC   3268106 . PMID   22235805.
13. "OMIM Entry - * 142989 - HOMEOBOX D13; HOXD13". www.omim.org. Retrieved 2020-03-01.

Further reading

• Johnson RL, Tabin CJ (September 1997). "Molecular models for vertebrate limb development". Cell. 90 (6): 979–90. doi: 10.1016/S0092-8674(00)80364-5 . PMID   9323126. S2CID   16213729.
• Goodman FR (October 2002). "Limb malformations and the human HOX genes". American Journal of Medical Genetics. 112 (3): 256–65. doi:10.1002/ajmg.10776. PMID   12357469.
• Scott MP (November 1992). "Vertebrate homeobox gene nomenclature". Cell. 71 (4): 551–3. doi:10.1016/0092-8674(92)90588-4. PMID   1358459. S2CID   13370372.
• D'Esposito M, Morelli F, Acampora D, Migliaccio E, Simeone A, Boncinelli E (May 1991). "EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5' end of HOX4 locus on chromosome 2". Genomics. 10 (1): 43–50. doi:10.1016/0888-7543(91)90482-T. PMID   1675198.
• Sarfarazi M, Akarsu AN, Sayli BS (August 1995). "Localization of the syndactyly type II (synpolydactyly) locus to 2q31 region and identification of tight linkage to HOXD8 intragenic marker". Human Molecular Genetics. 4 (8): 1453–8. doi:10.1093/hmg/4.8.1453. PMID   7581388.
• Muragaki Y, Mundlos S, Upton J, Olsen BR (April 1996). "Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13". Science. 272 (5261): 548–51. Bibcode:1996Sci...272..548M. doi:10.1126/science.272.5261.548. PMID   8614804. S2CID   25054058.
• Akarsu AN, Stoilov I, Yilmaz E, Sayli BS, Sarfarazi M (July 1996). "Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families". Human Molecular Genetics. 5 (7): 945–52. doi: 10.1093/hmg/5.7.945 . PMID   8817328.
• Warren ST (January 1997). "Polyalanine expansion in synpolydactyly might result from unequal crossing-over of HOXD13". Science. 275 (5298): 408–9. doi: 10.1126/science.275.5298.408 . PMID   9005557.
• Goodman FR, Mundlos S, Muragaki Y, Donnai D, Giovannucci-Uzielli ML, Lapi E, et al. (July 1997). "Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract". Proceedings of the National Academy of Sciences of the United States of America. 94 (14): 7458–63. Bibcode:1997PNAS...94.7458G. doi: 10.1073/pnas.94.14.7458 . PMC   23843 . PMID   9207113.
• Goodman F, Giovannucci-Uzielli ML, Hall C, Reardon W, Winter R, Scambler P (October 1998). "Deletions in HOXD13 segregate with an identical, novel foot malformation in two unrelated families". American Journal of Human Genetics. 63 (4): 992–1000. doi:10.1086/302070. PMC   1377502 . PMID   9758628.
• Limongi MZ, Pelliccia F, Gaddini L, Rocchi A (2000). "Clustering of two fragile sites and seven homeobox genes in human chromosome region 2q31→q32.1". Cytogenetics and Cell Genetics. 90 (1–2): 151–3. doi:10.1159/000015651 (inactive 2024-08-22). PMID   11060466. S2CID   35579702.
• Harrington JJ, Sherf B, Rundlett S, Jackson PD, Perry R, Cain S, et al. (May 2001). "Creation of genome-wide protein expression libraries using random activation of gene expression". Nature Biotechnology. 19 (5): 440–5. doi:10.1038/88107. PMID   11329013. S2CID   25064683.
• Goodman FR, Majewski F, Collins AL, Scambler PJ (February 2002). "A 117-kb microdeletion removing HOXD9-HOXD13 and EVX2 causes synpolydactyly". American Journal of Human Genetics. 70 (2): 547–55. doi:10.1086/338921. PMC   384929 . PMID   11778160.
• Kosaki K, Kosaki R, Suzuki T, Yoshihashi H, Takahashi T, Sasaki K, et al. (February 2002). "Complete mutation analysis panel of the 39 human HOX genes". Teratology. 65 (2): 50–62. doi:10.1002/tera.10009. PMID   11857506.
• Debeer P, Bacchelli C, Scambler PJ, De Smet L, Fryns JP, Goodman FR (November 2002). "Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13". Journal of Medical Genetics. 39 (11): 852–6. doi:10.1136/jmg.39.11.852. PMC   1735011 . PMID   12414828.
• Caronia G, Goodman FR, McKeown CM, Scambler PJ, Zappavigna V (April 2003). "An I47L substitution in the HOXD13 homeodomain causes a novel human limb malformation by producing a selective loss of function". Development. 130 (8): 1701–12. doi: 10.1242/dev.00396 . PMID   12620993.

External links

• HOXD13+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.