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Protein CRYM PDB 2i99.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CRYM, DFNA40, THBP, crystallin mu
External IDs MGI: 102675 HomoloGene: 1424 GeneCards: CRYM
RNA expression pattern
PBB GE CRYM 205489 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 16: 21.24 – 21.3 Mb Chr 7: 120.19 – 120.2 Mb
PubMed search [1] [2]
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Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a protein that in humans is encoded by the CRYM gene. Multiple alternatively spliced transcript variants have been found for this gene.[3][4]


Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles.[4]

Its enzyme function has been determined as a ketimine reductase, reducing cyclic ketimines to their reduced forms. Either NADH or NADPH can be used as cofactor. The most active substrate at pH 5.0 is aminoethylcysteine ketimine (AECK), however at neutral pH (pH 7.2) the most active substrate is 1-piperideine-2-carboxylate which is an important part of the pipecolic acid pathway. The active form of thyroxine, T3, has been found to be a potent inhibitor at nanomolar concentrations.[5]

Besides its role in lens biology, CRYM seems also to be involved in thyroid hormone signalling in other tissues. It could be demonstrated that CRYM mutations may cause deafness through thyroid hormone binding effects on the fibrocytes of the cochlea.[6] Disruption of the CRYM gene leads to decreased T3 concentrations in both tissues and serum without alteration of peripheral T3 action in vivo.[7][8]

The existence of intracellular thyroid hormone binding proteins has been postulated from mathematical modelling of pituitary-thyroid homeostasis.[9] Binding properties have been assumed to be similar to those of extracellular binding proteins,[10] however it is not clear, if THBP is the only intracellular thyroid hormone binding protein.


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Chen H, Phillips HA, Callen DF, Kim RY, Wistow GJ, Antonarakis SE (Feb 1993). "Localization of the human gene for mu-crystallin to chromosome 16p". Genomics. 14 (4): 1115–6. doi:10.1016/S0888-7543(05)80143-0. PMID 1478656. 
  4. ^ a b "Entrez Gene: CRYM crystallin, mu". 
  5. ^ Hallen A, Cooper AJ, Jamie JF, Haynes PA, Willows RD (February 2011). "Mammalian forebrain ketimine reductase identified as μ-crystallin; potential regulation by thyroid hormones". J Neurochem. 118 (3): no–no. doi:10.1111/j.1471-4159.2011.07220.x. PMID 21332720. 
  6. ^ Oshima A, Suzuki S, Takumi Y, Hashizume K, Abe S, Usami S (June 2006). "CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea". J. Med. Genet. 43 (6): e25. doi:10.1136/jmg.2005.034397. PMC 2564543Freely accessible. PMID 16740909. 
  7. ^ Abe S, Katagiri T, Saito-Hisaminato A, Usami S, Inoue Y, Tsunoda T, Nakamura Y (January 2003). "Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues". Am. J. Hum. Genet. 72 (1): 73–82. doi:10.1086/345398. PMC 420014Freely accessible. PMID 12471561. 
  8. ^ Suzuki S, Suzuki N, Mori J, Oshima A, Usami S, Hashizume K (April 2007). "micro-Crystallin as an intracellular 3,5,3'-triiodothyronine holder in vivo". Mol. Endocrinol. 21 (4): 885–94. doi:10.1210/me.2006-0403. PMID 17264173. 
  9. ^ Dietrich JW (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Entwicklung und klinische Anwendung eines nichtlinearen Modells. [The pituitary-thyroid control loop. Development and clinical application of a nonlinear model] (in German). Berlin: Logos-Verlag. ISBN 3-89722-850-5. 
  10. ^ Dietrich JW, Tesche A, Pickardt CR, Mitzdorf U (2004). "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis". Cybernetics and Systems. 35 (4): 315–31. doi:10.1080/01969720490443354. 

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