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Available structures
PDB Ortholog search: PDBe RCSB
Aliases PAX3, CDHS, HUP2, WS1, WS3, Pax3, paired box 3
External IDs OMIM: 606597 MGI: 97487 HomoloGene: 22494 GeneCards: PAX3
Gene location (Human)
Chromosome 2 (human)
Chr. Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for PAX3
Genomic location for PAX3
Band 2q36.1 Start 222,199,888 bp[1]
End 222,298,996 bp[1]
RNA expression pattern
PBB GE PAX3 207680 x at fs.png

PBB GE PAX3 216059 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 2: 222.2 – 222.3 Mb Chr 2: 78.1 – 78.2 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

PAX3 is a gene within the PAX family, a group of transcription factors consisting of proteins binding to DNA sequences to control gene transcription. Pax3 is important in embryonic development because Pax3 is active in neural crest cells. In conjunction with Msx1, Pax3 guides the expression of Snail1 and Snail2 down-regulating adhesion molecules. This allows neural crest cells to become mesenchymal cells that migrate throughout the body and become bones and muscles around the face, the parasympathetic nervous system, and other structural components. As a result, mutations within Pax3 generally result in developmental malformations because neural crest cells cannot move to the necessary parts of the body to complete their function. Craniofacial-deafness-hand syndrome is an example of an autosomal dominant disease resulting from a missense mutation in exon2 of Pax3. This mutation results in replacing the amino acid asparagine with lysine, inhibiting the Pax3 protein from binding to the necessary DNA.[5][6] Craniofacial-deafness-hand syndrome has distinctive symptoms, such as an underdeveloped nasal bone, a small mouth and upper-jaw, pursed lips, and wide spaced eyes with narrowed eye openings. Hearing loss and deformities in hand muscles are common. Hand abnormalities typically present themselves as angled and bent fingers. Depending on the severity, finger and hand movement can be limited. Despite these physical malformations, individuals have normal intelligence and an active life.[5][7] Diagnosis involves genotyping and collaborative efforts from orthopedists, pediatricians, and ophthalmologists. While there are knockout models developed for Pax3, they focused on cancers rather than this syndrome.

PAX3 is a gene that belongs to the paired box (PAX) family of transcription factors.[8] This gene was formerly known as splotch.[9] PAX3 has been identified with ear, eye and facial development.[10] Mutations in it can cause Waardenburg syndrome types 1 and 3. It is expressed in early embryonic phases in dermatomyotome of paraxial mesoderm which it helps to demarcate. In that way PAX3 contributes to early striated muscle development since all myoblasts are derived from dermatomyotome of paraxial mesoderm.

Alternative splicing results in transcripts encoding isoforms with different C-termini.[8]

Role in rhabdomyosarcoma[edit]

A PAX3/FKHR fusion gene is often associated with the alveolar type of rhabdomyosarcoma,[11] a kind of cancer arisen from striated muscle cells. Translocation between chromosomes 2 & 13 produce fusion protein PAX3/FKHR which serves as a tumor marker in this type of RMS.Also in ARMS expressing PAX3/FKHR increased risk of metastasis to bone marrow and hence increased rate of failure and death were seen.


PAX3 has been shown to interact with MEOX1,[12] MEOX2[12] and SOX10[13][14] as well as phosphatidylcholine transfer protein (PCTP).[15] PAX3 has an important relationship with c-met in myogenesis; if PAX3 is mutated, c-met expression may be inhibited or prevented altogether resulting in a lack of lateral migration.


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135903 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004872 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b Sommer, Annemarie; Bartholomew, Dennis W. (2003-11-15). "Craniofacial-deafness-hand syndrome revisited". American Journal of Medical Genetics. Part A. 123A (1): 91–94. doi:10.1002/ajmg.a.20501. ISSN 1552-4825. PMID 14556253. 
  6. ^ Asher, J. H.; Sommer, A.; Morell, R.; Friedman, T. B. (1996-01-01). "Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome". Human Mutation. 7 (1): 30–35. doi:10.1002/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T. ISSN 1059-7794. PMID 8664898. 
  7. ^ Sommer, A.; Young-Wee, T.; Frye, T. (1983-05-01). "Previously undescribed syndrome of craniofacial, hand anomalies, and sensorineural deafness". American Journal of Medical Genetics. 15 (1): 71–77. doi:10.1002/ajmg.1320150109. ISSN 0148-7299. PMID 6859126. 
  8. ^ a b "Entrez Gene: PAX3 paired box 3 [Homo sapiens]". 
  9. ^ "Entrez Gene: Pax3 paired box gene 3 [Mus musculus]". 
  10. ^
  11. ^ Begum S, Emami N, Emani N, et al. (March 2005). "Cell-type-specific regulation of distinct sets of gene targets by Pax3 and Pax3/FKHR". Oncogene. 24 (11): 1860–72. doi:10.1038/sj.onc.1208315. PMID 15688035. 
  12. ^ a b Stamataki D, Kastrinaki M, Mankoo BS, Pachnis V, Karagogeos D (June 2001). "Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors". FEBS Lett. 499 (3): 274–8. doi:10.1016/S0014-5793(01)02556-X. PMID 11423130. 
  13. ^ Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID 12668617. 
  14. ^ Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (August 2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID 10942418. 
  15. ^ Kanno K, Wu MK, Agate DA, Fanelli BK, Wagle N, Scapa EF, Ukomadu C, Cohen DE (October 2007). "Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2". J. Biol. Chem. 282 (42): 30728–36. doi:10.1074/jbc.M703745200. PMID 17704541. 

Further reading[edit]

External links[edit]