The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

USP9X  -  ubiquitin specific peptidase 9, X-linked

Homo sapiens

Synonyms: DFFRX, Deubiquitinating enzyme FAF-X, FAF, FAM, Fat facets in mammals, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of USP9X

  • Dominantly inherited familial amyloidosis, Finnish type (FAF) is caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin (GSN) [1].
  • Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of familial amyloid polyneuropathy [2].
  • Gelsolin-related amyloidosis, also called familial amyloidosis, Finnish type (FAF) is an autosomal dominantly inherited disorder characterized by progressive polyneuropathy and corneal lattice dystrophy [3].
  • We have recently shown that in a Danish and a Czech family with a clinical syndrome similar to FAF, including corneal lattice dystrophy, cranial neuropathy and skin changes, the disease is caused by another mutation at the same position, namely 654G-T predicting a Try-for-Asp substitution at 187 in secreted gelsolin [4].
  • Orthostatic hypotension was found in 9 of 28 FAF patients, but only in 3 of 69 controls [5].

High impact information on USP9X

  • We found the same mutation in a Dutch family but a Danish FAF family had a G654T mutation, predicting Asp to Tyr at residue 187 [1].
  • We found a mutation (adenine for guanine) at nucleotide 654 of the gelsolin gene in genomic DNA isolated from five FAF patients [2].
  • The mutation and consequent amino acid substitution may lead to the development of FAF [2].
  • These two loci have been termed DFFRX and DFFRY for Drosophila fat facets related X and Y. The major transcript detected by EST 221 is-8 kb in size and is expressed widely in a range of 16 human adult tissues [6].
  • The association between Itch and FAM/USP9X was confirmed in vitro by glutathione S-transferase pulldown and in vivo through coimmunoprecipation [7].

Chemical compound and disease context of USP9X

  • The Asp 187-->Asn (D187N) Asp 187-->Tyr (D187Y) gelsolin mutations facilitate two proteolytic cuts in the parent protein generating a 71-residue fragment that forms amyloid fibrils in humans, putatively causing Finnish type familial amyloidosis (FAF) [8].
  • A fluid-accumulating factor (FAF in the ligated rabbit ileal loop test) from a strain of non-O1 Vibrio cholerae not producing cholera toxin-like enterotoxin (CTLT) was partially purified by ammonium sulfate precipitation, gel filtration with Sephadex G-100, and DEAE cellulose column chromatography [9].

Biological context of USP9X

  • RESULTS: The expression of USP9Y, USP9X and DDX3Y was found in all the specimens tested, whereas DDX3Yt1 expression was diminished or undetectable in several biopsies with impaired spermatogenesis [10].
  • These results thus suggest that in addition to vesicular trafficking, DCX may play a role in the regulation of cell adhesion via its interaction with DFFRX in migrating and differentiating neurons [11].
  • To study the origin of the gelsolin mutation in these patients we performed haplotype analysis in 10 Finnish and 2 Japanese FAF families [12].
  • Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of amyloidosis which is related to a point mutation in the gelsolin gene localized on chromosome 9 [13].
  • BACKGROUND: Familial amyloidosis of the Finnish type (FAF, Finnish hereditary amyloidosis) is caused by a 654G-A mutation in the gelsolin gene on chromosome 9 resulting in the expression of mutant Asn-187 gelsolin which is abnormally proteolytically processed generating amyloidogenic fragments that polymerize into amyloid fibrils [4].

Anatomical context of USP9X

  • We also show that DFFRX associates with microtubules at specific subcellular compartments, including those enriched in DCX [11].
  • Rabbit polyclonal antibodies raised to the FAF amyloid not only immunostain the amyloid but also LBs in the cortex and substantia nigra of Parkinson's and diffuse LB disease brains [14].
  • Our original FAF patient was demented, and neuropathological analysis showed Alzheimer type brain lesions associated with both classical and cortical Lewy bodies [13].
  • Local production, especially in the cornea, conjunctiva, sclera, and ciliary muscle, and systemic deposition, particularly in blood vessles and in the sclera, may contribute to amyloid deposits in FAF [15].
  • We report autonomic nervous system and cardiac findings in a study of 30 FAF patients (18 females, 12 males aged 27-74 years; mean 53.9 years) [5].

Associations of USP9X with chemical compounds

  • Delta FAF to all dosages of Verap correlated positively with basal plasma epinephrine concentration in EH [16].
  • Autopsy eyes from three patients with FAF and ten control eyes were studied by Congo red staining and with antibodies to the nonmutated part of gelsolin (GS-2C4), the mutated gelsolin Asn-187 fragment (AGel), and amyloid-P component (AP) [15].
  • The guanine-to-adenine transversion was found in all FAF patients tested, but in none of the control subjects [17].
  • NE spillover into the forearm circulation was estimated as the product of delta VA-NE and FAF after three clonidine infusions [18].
  • For control group, IVM oocytes were fertilized using frozen-thawed camel spermatozoa separated by swim-up method then suspended in Fert-TALP medium supplemented with 6 mg/ml BSA (FAF) + 10 mug/ml heparin [19].

Other interactions of USP9X

  • DFFRX is thought to deubiquitinate specific substrates including beta-catenin, preventing their degradation by the proteasome [11].
  • Genotype-phenotype correlations suggest that the presence of a single copy of the DFFRX gene, previously postulated as a gene involved in the ovarian failure seen in Turner syndrome, may be compatible with normal ovarian function, and that there may be a gene for Turner-like features located in distal Xp22.3 [20].

Analytical, diagnostic and therapeutic context of USP9X

  • Immunohistochemistry showed that antibodies directed against residues 231-242 of secreted gelsolin, representing the carboxy terminus of the sequence forming the amyloid protein (residues 173-243) laid down in the tissues in a fibrillar form in FAF, specifically labelled the amyloid deposited in rectum and skin in the Danish (654G-T) subtype [4].


  1. Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187. de la Chapelle, A., Tolvanen, R., Boysen, G., Santavy, J., Bleeker-Wagemakers, L., Maury, C.P., Kere, J. Nat. Genet. (1992) [Pubmed]
  2. Mutation in gelsolin gene in Finnish hereditary amyloidosis. Levy, E., Haltia, M., Fernandez-Madrid, I., Koivunen, O., Ghiso, J., Prelli, F., Frangione, B. J. Exp. Med. (1990) [Pubmed]
  3. Toward understanding the pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment. Paunio, T., Kangas, H., Kalkkinen, N., Haltia, M., Palo, J., Peltonen, L. Hum. Mol. Genet. (1994) [Pubmed]
  4. Danish type gelsolin related amyloidosis: 654G-T mutation is associated with a disease pathogenetically and clinically similar to that caused by the 654G-A mutation (familial amyloidosis of the Finnish type). Maury, C.P., Liljeström, M., Boysen, G., Törnroth, T., de la Chapelle, A., Nurmiaho-Lassila, E.L. J. Clin. Pathol. (2000) [Pubmed]
  5. Autonomic nervous system and cardiac involvement in familial amyloidosis, Finnish type (FAF). Kiuru, S., Matikainen, E., Kupari, M., Haltia, M., Palo, J. J. Neurol. Sci. (1994) [Pubmed]
  6. The Drosophila developmental gene fat facets has a human homologue in Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2. Jones, M.H., Furlong, R.A., Burkin, H., Chalmers, I.J., Brown, G.M., Khwaja, O., Affara, N.A. Hum. Mol. Genet. (1996) [Pubmed]
  7. The Ubiquitin Ligase Itch Is Auto-ubiquitylated in Vivo and in Vitro but Is Protected from Degradation by Interacting with the Deubiquitylating Enzyme FAM/USP9X. Mouchantaf, R., Azakir, B.A., McPherson, P.S., Millard, S.M., Wood, S.A., Angers, A. J. Biol. Chem. (2006) [Pubmed]
  8. The amyloidogenicity of gelsolin is controlled by proteolysis and pH. Ratnaswamy, G., Koepf, E., Bekele, H., Yin, H., Kelly, J.W. Chem. Biol. (1999) [Pubmed]
  9. Production and partial purification of a fluid-accumulating factor of non-O1 Vibrio cholerae. Gyobu, Y., Kodama, H., Uetake, H. Microbiol. Immunol. (1988) [Pubmed]
  10. Expression profile of AZF genes in testicular biopsies of azoospermic men. Kleiman, S.E., Yogev, L., Hauser, R., Botchan, A., Maymon, B.B., Paz, G., Yavetz, H. Hum. Reprod. (2007) [Pubmed]
  11. Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes. Friocourt, G., Kappeler, C., Saillour, Y., Fauchereau, F., Rodriguez, M.S., Bahi, N., Vinet, M.C., Chafey, P., Poirier, K., Taya, S., Wood, S.A., Dargemont, C., Francis, F., Chelly, J. Mol. Cell. Neurosci. (2005) [Pubmed]
  12. Haplotype analysis in gelsolin-related amyloidosis reveals independent origin of identical mutation (G654A) of gelsolin in Finland and Japan. Paunio, T., Sunada, Y., Kiuru, S., Makishita, H., Ikeda, S., Weissenbach, J., Palo, J., Peltonen, L. Hum. Mutat. (1995) [Pubmed]
  13. Gelsolin variant and beta-amyloid co-occur in a case of Alzheimer's with Lewy bodies. Haltia, M., Ghiso, J., Wisniewski, T., Kiuru, S., Miller, D., Frangione, B. Neurobiol. Aging (1991) [Pubmed]
  14. Lewy bodies are immunoreactive with antibodies raised to gelsolin related amyloid-Finnish type. Wisniewski, T., Haltia, M., Ghiso, J., Frangione, B. Am. J. Pathol. (1991) [Pubmed]
  15. Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja's syndrome. Kivelä, T., Tarkkanen, A., Frangione, B., Ghiso, J., Haltia, M. Invest. Ophthalmol. Vis. Sci. (1994) [Pubmed]
  16. Enhanced vasodilatation in essential hypertension by calcium channel blockade with verapamil. Hulthén, U.L., Bolli, P., Amann, F.W., Kiowski, W., Bühler, F.R. Hypertension (1982) [Pubmed]
  17. Gelsolin gene mutation--at codon 187--in familial amyloidosis, Finnish: DNA-diagnostic assay. Haltia, M., Levy, E., Meretoja, J., Fernandez-Madrid, I., Koivunen, O., Frangione, B. Am. J. Med. Genet. (1992) [Pubmed]
  18. Prejunctional alpha 2-adrenoceptors and norepinephrine release in the forearm of normal humans. Kiowski, W., Hulthén, U.L., Ritz, R., Bühler, F.R. J. Cardiovasc. Pharmacol. (1985) [Pubmed]
  19. Morphology of Dromedary Camel Oocytes and their Ability to Spontaneous and Chemical Parthenogenetic Activation. Abdoon, A., Kandil, O., Berisha, B., Kliem, H., Schams, D. Reprod. Domest. Anim. (2007) [Pubmed]
  20. A study of females with deletions of the short arm of the X chromosome. James, R.S., Coppin, B., Dalton, P., Dennis, N.R., Mitchell, C., Sharp, A.J., Skuse, D.H., Thomas, N.S., Jacobs, P.A. Hum. Genet. (1998) [Pubmed]
WikiGenes - Universities