SOX9: Difference between revisions

'''Transcription factor SOX-9''' is a [[protein]] that in humans is encoded by the ''SOX9'' [[gene]].<ref name="pmid8348155">{{cite journal | vauthors = Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, Goodpasture C, Guldberg P, Held KR, Reinwein H | display-authors = 6 | title = Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1 | journal = Nature Genetics | volume = 4 | issue = 2 | pages = 170–4170–174 | date = June 1993 | pmid = 8348155 | doi = 10.1038/ng0693-170 | s2cid = 12263655 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6662}}</ref>

SOX-9 recognizes the sequence CCTTGAG along with other members of the [[HMG-box]] class [[DNA-binding domain|DNA-binding]] proteins. It is expressed by proliferating but not hypertrophic chondrocytes that is essential for differentiation of precursor cells into [[chondrocytes]]<ref>{{cite book | vauthors = Kumar V, Abbas AK, Aster JC |title=Robbins and Cotran pathologic basis of disease |isbn=9780808924500 |page=1182 |edition=Ninth|last1=Kumar |first1=Vinay |last2=Abbas |first2=Abul K. |last3=Aster |first3=Jon C. |year=2015 |publisher=Elsevier/Saunders }}</ref> and, with [[steroidogenic factor 1]], regulates transcription of the anti-Müllerian hormone ([[Anti-Müllerian hormone|AMH]]) gene.<ref name="entrez"/>

SOX-9 also plays a pivotal role in male sexual development; by working with Sf1, SOX-9 can produce AMH in [[Sertoli cell]]s to inhibit the creation of a female reproductive system.<ref name="pmid9774680">{{cite journal | vauthors = De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P | display-authors = 6 | title = Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene | journal = Molecular and Cellular Biology | volume = 18 | issue = 11 | pages = 6653–656653–6665 | date = November 1998 | pmid = 9774680 | pmc = 109250 | doi = 10.1128/mcb.18.11.6653 }}</ref> It also interacts with a few other genes to promote the development of male sexual organs. The process starts when the transcription factor [[testis determining factor]] (encoded by the sex-determining region [[SRY]] of the [[Y chromosome]]) activates SOX-9 activity by binding to an [[enhancer (genetics)|enhancer]] sequence [[Upstream and downstream (DNA)|upstream]] of the gene.<ref name="Moniot">{{cite journal | vauthors = Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, Marzi L, Cohen-Solal A, Georg I, Klattig J, Englert C, Kim Y, Capel B, Eguchi N, Urade Y, Boizet-Bonhoure B, Poulat F | display-authors = 6 | title = The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation | journal = Development | volume = 136 | issue = 11 | pages = 1813–211813–1821 | date = June 2009 | pmid = 19429785 | pmc = 4075598 | doi = 10.1242/dev.032631 }}</ref> Next, Sox9SOX9 activates [[FGF9]] and forms feedforward loops with FGF9<ref name="pmid16700629">{{cite journal | vauthors = Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R, Capel B | display-authors = 6 | title = Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination | journal = PLOS Biology | volume = 4 | issue = 6 | pages = e187 | date = June 2006 | pmid = 16700629 | pmc = 1463023 | doi = 10.1371/journal.pbio.0040187 | doi-access = free }}</ref> and [[PGD2]].<ref name="Moniot"/> These loops are important for producing SOX-9; without these loops, SOX-9 would run out and the development of a female would almost certainly ensue. Activation of FGF9 by SOX-9 starts vital processes in male development, such as the creation of [[testis cords]] and the multiplication of [[Sertoli cell]]s.<ref name="pmid16700629"/> The association of SOX-9 and [[Dax1]] actually creates Sertoli cells, another vital process in male development.<ref name="pmid15944188">{{cite journal | vauthors = Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM | title = Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells | journal = Development | volume = 132 | issue = 13 | pages = 3045–543045–3054 | date = July 2005 | pmid = 15944188 | doi = 10.1242/dev.01890 | doi-access = free }}</ref> In the brain development, its murine ortholog Sox-9 induces the expression of [[WWP1|Wwp1]], [[WWP2|Wwp2]], and miR-140 to regulate cortical plate entry of newly born nerve cells, and regulate axon branching and axon formation in cortical neurons.<ref>{{cite journal | vauthors = Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, Rusanova A, Altas B, Piepkorn L, Bessa P, Schaub T, Zhang X, Rabe T, Ripamonti S, Rosário M, Akiyama H, Jahn O, Kobayashi T, Hoshino M, Tarabykin V, Kawabe H | display-authors = 6 | title = Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140 | journal = Neuron | volume = 100 | issue = 5 | pages = 1097–1115.e15 | date = December 2018 | pmid = 30392800 | doi = 10.1016/j.neuron.2018.10.008 | doi-access = free }}</ref>

In adult articular chondrocytes, [[siRNA]]-mediated knockdown of SOX-9 or [[RTL3]] results in the downregulation of the other and reduced [[type II collagen]] ([[COL2A1]]) mRNA and protein expression.<ref>{{Citecite journal |last1 vauthors = Ball |first1=HopeHC, C. |last2=Ansari |first2=Mohammad Y.MY, |last3=Ahmad |first3=NashrahN, |last4=Novak |first4=KimberlyK, |last5=Haqqi TM |first5=Tariq M.title |date=November 2021 |title=A retrotransposon gag-like-3 gene RTL3 and SOX-9 co-regulate the expression of COL2A1 in chondrocytes | journal = Connective Tissue Research | volume = 62 | issue = 6 | pages = 615–628 |doi date =10.1080/03008207.2020.1828380 November 2021 |issn pmid =1607-8438 33043724 | pmc = 8404968 |pmid doi =33043724 10.1080/03008207.2020.1828380 }}</ref>

Mutations lead to the skeletal malformation syndrome [[campomelic dysplasia]], frequently with autosomal sex-reversal<ref name="entrez" /> and [[cleft palate]].<ref name="Dixon_2011">{{cite journal | vauthors = Dixon MJ, Marazita ML, Beaty TH, Murray JC | title = Cleft lip and palate: understanding genetic and environmental influences | journal = Nature Reviews. Genetics | volume = 12 | issue = 3 | pages = 167–78167–178 | date = March 2011 | pmid = 21331089 | pmc = 3086810 | doi = 10.1038/nrg2933 }}</ref>

SOX9 sits in a [[gene desert]] on 17q24 in humans. Deletions, disruptions by [[chromosomal translocation|translocation]] breakpoints and a single point mutation of highly conserved non-coding elements located > 1 [[Base pair#Length measurements|Mb]] from the transcription unit on either side of SOX9 have been associated with [[Pierre Robin syndrome|Pierre Robin Sequence]], often with a [[cleft palate]].<ref name="Dixon_2011"/><ref name="pmid19234473">{{cite journal | vauthors = Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Roest Crollius H, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S | display-authors = 6 | title = Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence | journal = Nature Genetics | volume = 41 | issue = 3 | pages = 359–64359–364 | date = March 2009 | pmid = 19234473 | doi = 10.1038/ng.329 | s2cid = 29933548 }}</ref>

The Sox9SOX9 protein has been implicated in both initiation and progression of multiple solid tumors.<ref name="The versatile functions of Sox9 in">{{cite journal |last1 vauthors = Jo |first1=A, |last2=Denduluri |first2=S, |last3=Zhang |first3=B, |last4=Wang |first4=Z, |last5=Yin |first5=L, |last6=Yan |first6=Z, |last7=Kang |first7=R, |last8=Shi |first8=LL, |last9=Mok |first9=J, |last10=Lee |first10=MJ, |last11=Haydon |first11=RC | title = The versatile functions of Sox9 in development, stem cells, and human diseases. | journal = Genes & Diseases |date=December 2014 |volume = 1 | issue = 2 | pages = 149–161 | date = December 2014 | pmid = 25685828 | pmc = 4326072 | doi = 10.1016/j.gendis.2014.09.004 |pmid=25685828|pmc=4326072 }}</ref> Its role as a master regulator of [[morphogenesis]] during [[Development of the human body|human development]] makes it an ideal candidate for perturbation in malignant tissues. Specifically, Sox9SOX9 appears to induce invasiveness and therapy-resistance in prostate,<ref name="Transient Sox9 Expression Facilitat">{{cite journal |last1 vauthors = Nouri |first1=M, |last2=Massah |first2=S, |last3=Caradec |first3=J, |last4=Lubik |first4=AA, |last5=Li |first5=N, |last6=Truong |first6=S, |last7=Lee |first7=AR, |last8=Fazli |first8=L, |last9=Ramnarine |first9=VR, |last10=Lovnicki |first10=JM, |last11=Moore |first11=J, |last12=Wang |first12=M, |last13=Foo |first13=J, |last14=Gleave |first14=ME, |last15=Hollier |first15=BG, |last16=Nelson |first16=C, |last17=Collins |first17=C, |last18=Dong |first18=X, |last19=Buttyan |first19=R | title = Transient Sox9 Expression Facilitates Resistance to Androgen-Targeted Therapy in Prostate Cancer. | journal = Clinical Cancer Research |date=9 January 2020 |volume = 26 | issue = 7 | pages = 1678–1689 | date = April 2020 | pmid = 31919137 | doi = 10.1158/1078-0432.CCR-19-0098 |pmid=31919137| doi-access = free }}</ref> colorectal,<ref>{{cite journal |last1 vauthors = Prévostel |first1=C, |last2=Blache |first2=P | title = The dose-dependent effect of SOX9 and its incidence in colorectal cancer. | journal = European Journal of Cancer |date=November 2017 |volume = 86 | pages = 150–157 | date = November 2017 | pmid = 28988015 | doi = 10.1016/j.ejca.2017.08.037 |pmid=28988015}}</ref> breast<ref>{{cite journal |last1 vauthors = Grimm |first1=D, |last2=Bauer |first2=J, |last3=Wise |first3=P, |last4=Krüger |first4=M, |last5=Simonsen |first5=U, |last6=Wehland |first6=M, |last7=Infanger |first7=M, |last8=Corydon |first8=TJ | title = The role of SOX family members in solid tumours and metastasis. | journal = Seminars in Cancer Biology |date=23 Marchvolume 2019 |volume= 67 | issue = Pt 1 | pages = 122–153 | date = December 2020 | pmid = 30914279 | doi = 10.1016/j.semcancer.2019.03.004 |pmid hdl-access =30914279 free | doi-access = free | hdl = 21.11116/0000-0007-D3EE-F |hdl-access=free }}</ref> and other cancers, and therefore promotes lethal metastasis.<ref>{{cite journal |last1 vauthors = Aguilar-Medina |first1=M, |last2=Avendaño-Félix |first2=M, |last3=Lizárraga-Verdugo |first3=E, |last4=Bermúdez |first4=M, |last5=Romero-Quintana |first5=JG, |last6=Ramos-Payan |first6=R, |last7=Ruíz-García |first7=E, |last8=López-Camarillo |first8=C | title = SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer. | journal = Journal of Oncology |date=2019 |volume = 2019 | pages = 6754040 |doi date =10.1155/ 2019/6754040 | pmid = 31057614 | pmc = 6463569 | doi = 10.1155/2019/6754040 | doi-access = free }}</ref> Many of these oncogenic effects of Sox9SOX9 appear dose -dependent.<ref>{{cite journal |last1 vauthors = Yang |first1=X, |last2=Liang |first2=R, |last3=Liu |first3=C, |last4=Liu |first4=JA, |last5=Cheung |first5=MPLMP, |last6=Liu |first6=X, |last7=Man |first7=OY, |last8=Guan |first8=XY, |last9=Lung |first9=HL, |last10=Cheung |first10=M | title = SOX9 is a dose-dependent metastatic fate determinant in melanoma. | journal = Journal of Experimental & Clinical Cancer Research |date=14 Januaryvolume 2019= |volume=38 | issue = 1 | pages = 17 | date = January 2019 | pmid = 30642390 | pmc = 6330758 | doi = 10.1186/s13046-018-0998-6 |pmid=30642390|pmc=6330758 |doi-access = free }}</ref><ref name="Transient Sox9 Expression Facilitat"/><ref name="The versatile functions of Sox9 in"/>

== SOX9 localisationlocalization and dynamics ==

SOX9 is mostly localisedlocalizatied in the nucleus and it is highly mobile. Studies in chondrocyte cell line has revealed nearly 50% of SOX9 is bound to DNA and it is directly regulated by external factors. Its half-time of residence on DNA is ~14 seconds.<ref name="pmid30465885">{{cite journal | vauthors = Govindaraj K, Hendriks J, Lidke DS, Karperien M, Post JN | title = Changes in Fluorescence Recovery After Photobleaching (FRAP) as an indicator of SOX9 transcription factor activity | journal = Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | volume = 1862 | issue = 1 | pages = 107–117 | date = January 2019 | pmid = 30465885 | doi = 10.1016/j.bbagrm.2018.11.001 | doi-access = free }}</ref>

==Role in sexSexual reversalDifferentiation==

SOX9 helps channel SRY activation in sexual differentiation. [[Mutation]]s in Sox9SOX9 or any associated genes can cause a reversal of sex and [[hermaphroditism]] (or [[intersex]]uality in humans). If Fgf9FGF9, which is activated by Sox9SOX9, is not present, a [[fetus]] with both X and Y [[chromosome]]s canwill developbecome female gonads;.<ref name="Moniot"/> the same is true if [[Dax1|DAX1]] is not present.<ref name="pmid15944188" /> The related phenomena of hermaphroditism can be caused by unusual activity of the SRY in [[XX male syndrome]], usually when it's translocated onto the X-chromosome and its activity is only activated in some cells.<ref name="pmid10602113">{{cite journal | vauthors = Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F | title = SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite | journal = American Journal of Medical Genetics | volume = 90 | issue = 1 | pages = 25–825–28 | date = January 2000 | pmid = 10602113 | doi = 10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5 }}</ref> Mutation or deletion of SOX9 could cause an XY fetus to be female because SOX9 is a critical effector gene that works because of the SRY gene to differentiate Sertoli cells and drive testis formation in males.<ref name="Normal Levels of Sox9 Expression in"/>

SOX9 has been shown to [[Protein-protein interaction|interact]] with [[steroidogenic factor 1]],<ref name="pmid9774680" /> [[MED12]],<ref name="pmid12136106">{{cite journal | vauthors = Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S | display-authors = 6 | title = SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex | journal = Nucleic Acids Research | volume = 30 | issue = 14 | pages = 3245–523245–3252 | date = July 2002 | pmid = 12136106 | pmc = 135763 | doi = 10.1093/nar/gkf443 }}</ref> [[MAF (gene)|MAF]],<ref name="pmid12381733">{{cite journal | vauthors = Huang W, Lu N, Eberspaecher H, De Crombrugghe B | title = A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene | journal = The Journal of Biological Chemistry | volume = 277 | issue = 52 | pages = 50668–7550668–50675 | date = December 2002 | pmid = 12381733 | doi = 10.1074/jbc.M206544200 | doi-access = free }}</ref> [[SWI/SNF]], [[KMT2C|MLL3]] and [[MLL4]].<ref>{{Citecite journal |last1 vauthors = Yang |first1=YihaoY, |last2=Gomez |first2=NicholasN, |last3=Infarinato |first3=NicoleN, |last4=Adam |first4=ReneRC, C. |last5=Sribour |first5=MeganM, |last6=Baek |first6=InwhaI, |last7=Laurin |first7=MélanieM, |last8=Fuchs |first8=ElaineE |date=2023-07-24 |title = The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates | journal = Nature Cell Biology | volume = 25 | issue = 8 |language=en |pages = 1185–1195 |doi date =10.1038/s41556-023-01184-y August 2023 | pmid = 37488435 | pmc = 10415178 |issn doi =1476 10.1038/s41556-4679023-01184-y | doi-access = free }}</ref>

* {{cite journal | vauthors = Ninomiya S, Narahara K, Tsuji K, Yokoyama Y, Ito S, Seino Y | title = Acampomelic campomelic syndrome and sex reversal associated with de novo t(12;17) translocation | journal = American Journal of Medical Genetics | volume = 56 | issue = 1 | pages = 31–431–34 | date = March 1995 | pmid = 7747782 | doi = 10.1002/ajmg.1320560109 }}

* {{cite journal | vauthors = Lefebvre V, de Crombrugghe B | title = Toward understanding SOX9 function in chondrocyte differentiation | journal = Matrix Biology | volume = 16 | issue = 9 | pages = 529–40529–540 | date = March 1998 | pmid = 9569122 | doi = 10.1016/S0945-053X(98)90065-8 }}

* {{cite book | author=Harley VR |title=The Genetics and Biology of Sex Determination |chapter=The Molecular Action of Testis‐DeterminingTestis-Determining Factors SRY and SOX9 |volume=244 |pages= 57–66; discussion 66–7, 79–85, 253–7 |year= 2002 |pmid= 11990798 |doi=10.1002/0470868732.ch6 |series=Novartis Foundation Symposia |isbn=9780470843468 }}

* {{cite journal | vauthors = Kwok C, Weller PA, Guioli S, Foster JW, Mansour S, Zuffardi O, Punnett HH, Dominguez-Steglich MA, Brook JD, Young ID | display-authors = 6 | title = Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal | journal = American Journal of Human Genetics | volume = 57 | issue = 5 | pages = 1028–361028–1036 | date = November 1995 | pmid = 7485151 | pmc = 1801368 }}

* {{cite journal | vauthors = Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanović M, Weissenbach J, Mansour S, Young ID, Goodfellow PN | display-authors = 6 | title = Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene | journal = Nature | volume = 372 | issue = 6506 | pages = 525–30525–530 | date = December 1994 | pmid = 7990924 | doi = 10.1038/372525a0 | s2cid = 1472426 | bibcode = 1994Natur.372..525F | s2cid = 1472426 }}

* {{cite journal | vauthors = Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Bricarelli FD, Keutel J, Hustert E, Wolf U, Tommerup N, Schempp W, Scherer G | display-authors = 6 | title = Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9 | journal = Cell | volume = 79 | issue = 6 | pages = 1111–201111–1120 | date = December 1994 | pmid = 8001137 | doi = 10.1016/0092-8674(94)90041-8 | s2cid = 24982682 }}

* {{cite journal | vauthors = Südbeck P, Schmitz ML, Baeuerle PA, Scherer G | title = Sex reversal by loss of the C-terminal transactivation domain of human SOX9 | journal = Nature Genetics | volume = 13 | issue = 2 | pages = 230–2230–232 | date = June 1996 | pmid = 8640233 | doi = 10.1038/ng0696-230 | s2cid = 22617889 }}

* {{cite journal | vauthors = Cameron FJ, Hageman RM, Cooke-Yarborough C, Kwok C, Goodwin LL, Sillence DO, Sinclair AH | title = A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal | journal = Human Molecular Genetics | volume = 5 | issue = 10 | pages = 1625–301625–1630 | date = October 1996 | pmid = 8894698 | doi = 10.1093/hmg/5.10.1625 | doi-access = free }}

* {{cite journal | vauthors = Meyer J, Südbeck P, Held M, Wagner T, Schmitz ML, Bricarelli FD, Eggermont E, Friedrich U, Haas OA, Kobelt A, Leroy JG, Van Maldergem L, Michel E, Mitulla B, Pfeiffer RA, Schinzel A, Schmidt H, Scherer G | display-authors = 6 | title = Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations | journal = Human Molecular Genetics | volume = 6 | issue = 1 | pages = 91–891–98 | date = January 1997 | pmid = 9002675 | doi = 10.1093/hmg/6.1.91 | doi-access = free }}

* {{cite journal | vauthors = Cameron FJ, Sinclair AH | title = Mutations in SRY and SOX9: testis-determining genes | journal = Human Mutation | volume = 9 | issue = 5 | pages = 388–95388–395 | year = 1997 | pmid = 9143916 | doi = 10.1002/(SICI)1098-1004(1997)9:5<388::AID-HUMU2>3.0.CO;2-0 | s2cid = 45387678 }}

* {{cite journal | vauthors = Wunderle VM, Critcher R, Hastie N, Goodfellow PN, Schedl A | title = Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 18 | pages = 10649–5410649–10654 | date = September 1998 | pmid = 9724758 | pmc = 27949 | doi = 10.1073/pnas.95.18.10649 | bibcodedoi-access = 1998PNAS...9510649Wfree | doi-accessbibcode = free1998PNAS...9510649W }}

* {{cite journal | vauthors = De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P | display-authors = 6 | title = Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene | journal = Molecular and Cellular Biology | volume = 18 | issue = 11 | pages = 6653–656653–6665 | date = November 1998 | pmid = 9774680 | pmc = 109250 | doi = 10.1128/mcb.18.11.6653 }}

* {{cite journal | vauthors = McDowall S, Argentaro A, Ranganathan S, Weller P, Mertin S, Mansour S, Tolmie J, Harley V | display-authors = 6 | title = Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24023–3024023–24030 | date = August 1999 | pmid = 10446171 | doi = 10.1074/jbc.274.34.24023 | doi-access = free }}

* {{cite journal | vauthors = Huang W, Zhou X, Lefebvre V, de Crombrugghe B | title = Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer | journal = Molecular and Cellular Biology | volume = 20 | issue = 11 | pages = 4149–584149–4158 | date = June 2000 | pmid = 10805756 | pmc = 85784 | doi = 10.1128/MCB.20.11.4149-4158.2000 }}

* {{cite journal | vauthors = Thong MK, Scherer G, Kozlowski K, Haan E, Morris L | title = Acampomelic campomelic dysplasia with SOX9 mutation | journal = American Journal of Medical Genetics | volume = 93 | issue = 5 | pages = 421–5421–425 | date = August 2000 | pmid = 10951468 | doi = 10.1002/1096-8628(20000828)93:5<421::AID-AJMG14>3.0.CO;2-5 }}

* {{cite journal | vauthors = Ninomiya S, Yokoyama Y, Teraoka M, Mori R, Inoue C, Yamashita S, Tamai H, Funato M, Seino Y | display-authors = 6 | title = A novel mutation (296 del G) of the SOX90 gene in a patient with campomelic syndrome and sex reversal | journal = Clinical Genetics | volume = 58 | issue = 3 | pages = 224–7224–227 | date = September 2000 | pmid = 11076045 | doi = 10.1034/j.1399-0004.2000.580310.x | s2cid = 28618271 }}

* {{cite journal | vauthors = Preiss S, Argentaro A, Clayton A, John A, Jans DA, Ogata T, Nagai T, Barroso I, Schafer AJ, Harley VR | display-authors = 6 | title = Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 30 | pages = 27864–7227864–27872 | date = July 2001 | pmid = 11323423 | doi = 10.1074/jbc.M101278200 | doi-access = free }}

== References ==