Details for: CRYM

Gene ID: 1428

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CRYM

Ensembl ID: ENSG00000103316

Description: crystallin mu

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural crest cell CL0011012
    CSI 19.64
    rCSI 15.53%
    PRS 81.94
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 11.13
    rCSI 42.08%
    PRS 76.02
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 10.95
    rCSI 39.42%
    PRS 73.75
  • lung neuroendocrine cell CL1000223
    CSI 10.21
    rCSI 15.1%
    PRS 91.35
  • tracheal goblet cell CL1000329
    CSI 9.45
    rCSI 20.63%
    PRS 92.01
  • glial cell CL0000125
    CSI 9.4
    rCSI 35.78%
    PRS 82.66
  • nasal mucosa goblet cell CL0002480
    CSI 9.39
    rCSI 10.9%
    PRS 90.16
  • brush cell of tracheobronchial tree CL0002075
    CSI 7.8
    rCSI 23.13%
    PRS 95.12
  • forebrain radial glial cell CL0013000
    CSI 7.78
    rCSI 24.97%
    PRS 89.34
  • secretory cell CL0000151
    CSI 7.78
    rCSI 8.11%
    PRS 88.42
  • melanocyte CL0000148
    CSI 7.16
    rCSI 5.3%
    PRS 85.39
  • erythrocyte CL0000232
    CSI 7.09
    rCSI 16.09%
    PRS 88.09
  • respiratory basal cell CL0002633
    CSI 6.55
    rCSI 6.78%
    PRS 91.18
  • Mueller cell CL0000636
    CSI 6.44
    rCSI 14.69%
    PRS 82.67
  • plasmacytoid dendritic cell, human CL0001058
    CSI 6.08
    rCSI 4.25%
    PRS 92.5
  • bronchial goblet cell CL1000312
    CSI 5.55
    rCSI 22.16%
    PRS 92.76
  • neural cell CL0002319
    CSI 5.43
    rCSI 20.51%
    PRS 74.04
  • club cell CL0000158
    CSI 5.41
    rCSI 7.93%
    PRS 84.74
  • cerebellar granule cell CL0001031
    CSI 4.95
    rCSI 7.27%
    PRS 84.09
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.86
    rCSI 3.77%
    PRS 92.16
  • bronchus fibroblast of lung CL2000093
    CSI 4.55
    rCSI 3.7%
    PRS 88.72
  • intestinal tuft cell CL0019032
    CSI 4.36
    rCSI 6.67%
    PRS 91.38
  • squamous epithelial cell CL0000076
    CSI 4.06
    rCSI 9.64%
    PRS 87.05
  • cerebral cortex neuron CL0010012
    CSI 4.05
    rCSI 16.51%
    PRS 82.21
  • kidney epithelial cell CL0002518
    CSI 4.03
    rCSI 7.7%
    PRS 96.18
  • lung secretory cell CL1000272
    CSI 3.95
    rCSI 9.79%
    PRS 89.94
  • multi-ciliated epithelial cell CL0005012
    CSI 3.78
    rCSI 3.77%
    PRS 83.75
  • goblet cell CL0000160
    CSI 3.76
    rCSI 3.55%
    PRS 87.27
  • epithelial cell of lung CL0000082
    CSI 3.69
    rCSI 3.06%
    PRS 90.26
  • respiratory goblet cell CL0002370
    CSI 3.4
    rCSI 37.01%
    PRS 92.61
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 3.35
    rCSI 11.02%
    PRS 77.74
  • mucus secreting cell CL0000319
    CSI 3.06
    rCSI 4.86%
    PRS 94.03
  • epithelial cell of proximal tubule CL0002306
    CSI 2.91
    rCSI 7.1%
    PRS 82.64
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.86
    rCSI 6.96%
    PRS 73.54
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.86
    rCSI 6.83%
    PRS 78.73
  • lung ciliated cell CL1000271
    CSI 2.82
    rCSI 3.26%
    PRS 83.69
  • cardiac muscle cell CL0000746
    CSI 2.81
    rCSI 4.03%
    PRS 81.45
  • respiratory suprabasal cell CL4033048
    CSI 2.78
    rCSI 3.56%
    PRS 91.23
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.74
    rCSI 16.16%
    PRS 76.29
  • enteroendocrine cell CL0000164
    CSI 2.45
    rCSI 3.35%
    PRS 88.09
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 2.42
    rCSI 5.24%
    PRS 78.33
  • acinar cell CL0000622
    CSI 2.13
    rCSI 3.13%
    PRS 94.73
  • direct pathway medium spiny neuron CL4023026
    CSI 1.88
    rCSI 45.04%
    PRS 73.54
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.84
    rCSI 44.51%
    PRS 73.79
  • regular atrial cardiac myocyte CL0002129
    CSI 1.7
    rCSI 5.47%
    PRS 86.15
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.69
    rCSI 2.02%
    PRS 75.81
  • platelet CL0000233
    CSI 1.64
    rCSI 6.82%
    PRS 86.1
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.61
    rCSI 1.45%
    PRS 88.26
  • tracheobronchial serous cell CL0019001
    CSI 1.6
    rCSI 6.92%
    PRS 92.17
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.55
    rCSI 9.67%
    PRS 83.03
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.46
    rCSI 2.36%
    PRS 76.86
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.45
    rCSI 4.54%
    PRS 77.16
  • medium spiny neuron CL1001474
    CSI 1.38
    rCSI 11.91%
    PRS 80.96
  • megakaryocyte CL0000556
    CSI 1.15
    rCSI 4.97%
    PRS 91.23
  • helper T cell CL0000912
    CSI 1.1
    rCSI 1.56%
    PRS 85.73
  • central nervous system neuron CL2000029
    CSI 0.46
    rCSI 3.37%
    PRS 80.55

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CRYM](/details-gene/1428) encodes mu-crystallin, a multifunctional protein with roles extending beyond its original discovery as a structural component of the lens in some species. It primarily functions as an NADPH-dependent ketimine reductase and a cytosolic thyroid hormone-binding protein, suggesting key roles in metabolism and hormone signaling ([Link](https://doi.org/10.1111/j.1471-4159.2011.07220.x), [Link](https://doi.org/10.1210/mend.11.11.9915)). **Overall**, its expression profile is highly specific, showing significant enrichment in diverse neural and secretory cell populations, including [neural crest cell](/details-cell/CL0011012)s and various glutamatergic neurons. Clinically, mutations in [CRYM](/details-gene/1428) are associated with nonsyndromic deafness ([OMIM:123740](https://omim.org/entry/123740)), underscoring its importance in auditory function ([Link](https://doi.org/10.1086/345398)). ## Cellular Roles and Expression Landscape The expression pattern of [CRYM](/details-gene/1428) highlights its specialized function primarily within the nervous system and in secretory tissues. **Overall**, the gene shows the highest significance in cells of the neural lineage, including [neural crest cell](/details-cell/CL0011012) (CSI: 19.64), [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) (CSI: 11.13), [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 10.95), and various [glial cell](/details-cell/CL0000125)s (CSI: 9.40) like [forebrain radial glial cell](/details-cell/CL0013000) and [Mueller cell](/details-cell/CL0000636). This is consistent with its role in binding thyroid hormones, which are critical for neurodevelopment and metabolism ([Link](https://doi.org/10.1111/j.1471-4159.2011.07220.x)). Beyond the nervous system, [CRYM](/details-gene/1428) is a significant marker for several types of [secretory cell](/details-cell/CL0000151)s. This includes high expression in [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 10.21), [tracheal goblet cell](/details-cell/CL1000329) (CSI: 9.45), and [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 9.39). This pattern suggests a role in metabolic processes or signaling specific to these specialized epithelial tissues. Its notable, albeit lower, significance in cell types such as [melanocyte](/details-cell/CL0000148)s and [erythrocyte](/details-cell/CL0000232)s points to a broader, though less prominent, role in other tissues. The general absence of high significance in major immune or muscle cell lineages suggests a highly specialized function outside of these systems. ## Pathways and Molecular Function The functional annotations for [CRYM](/details-gene/1428) are consistent with its dual identity as an enzyme and a binding protein. Its molecular functions are dominated by `Thyroid hormone binding` ([GO:0070324](https://www.ebi.ac.uk/QuickGO/term/GO:0070324)) and `NADP binding` ([GO:0050661](https://www.ebi.ac.uk/QuickGO/term/GO:0050661)), which underpins its enzymatic activity as a `Thiomorpholine-carboxylate dehydrogenase` ([GO:0047127](https://www.ebi.ac.uk/QuickGO/term/GO:0047127)). This enzymatic role places it within the `Lysine catabolism` pathway ([R-HSA-71064](https://reactome.org/content/detail/R-HSA-71064)). Biologically, [CRYM](/details-gene/1428) is involved in the `Thyroid hormone metabolic process` ([GO:0042403](https://www.ebi.ac.uk/QuickGO/term/GO:0042403)) and `Thyroid hormone transport` ([GO:0070327](https://www.ebi.ac.uk/QuickGO/term/GO:0070327)). This function is particularly relevant in the context of its high expression in neurons, where thyroid hormone signaling is vital for development and plasticity. Furthermore, its role in `Sensory perception of sound` ([GO:0007605](https://www.ebi.ac.uk/QuickGO/term/GO:0007605)) directly reflects the clinical phenotype of deafness associated with its mutation. The protein is primarily localized to the `Cytoplasm` ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) and `Cytosol` ([GO:0005829](https://www.ebi.ac.uk/QuickGO/term/GO:0005829)), but also found in the `Nucleus` ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)), where it may act as a `Transcription corepressor` ([GO:0003714](https://www.ebi.ac.uk/QuickGO/term/GO:0003714)). ## Research Directions The specific expression patterns and known functions of [CRYM](/details-gene/1428) raise several important questions about its precise physiological roles. **Proposed Hypotheses:** 1. The high expression of [CRYM](/details-gene/1428) in glutamatergic cortical neurons suggests its primary role in the central nervous system is to buffer cytosolic thyroid hormone levels, thereby modulating neuronal excitability and metabolic rate in an activity-dependent manner. 2. Given its enzymatic function in lysine catabolism and its association with deafness ([Link](https://doi.org/10.1086/345398)), [CRYM](/details-gene/1428) may be critical for preventing the accumulation of potentially ototoxic metabolic intermediates within the specialized cells of the inner ear. Loss of this enzymatic activity, rather than its hormone-binding function, could be the primary driver of the deafness phenotype. **Key Experimental Approach:** To test the second hypothesis, a knock-in mouse model could be generated expressing a catalytically dead mutant of [CRYM](/details-gene/1428) that retains its thyroid-hormone binding capacity. Auditory function could be assessed in these mice using auditory brainstem response (ABR) testing. If the mice develop a hearing deficit similar to that of a full knockout model, it would support the hypothesis that the enzymatic activity is essential. Further, metabolomic analysis of inner ear tissue from these mice using liquid chromatography-mass spectrometry (LC-MS) could identify the specific metabolic byproducts that accumulate in the absence of [CRYM](/details-gene/1428) function, potentially identifying the ototoxic agent. **Therapeutic Potential:** As loss-of-function mutations in [CRYM](/details-gene/1428) are linked to pathology (hereditary deafness), the gene represents a potential target for restorative therapies. For specific forms of nonsyndromic deafness, AAV-mediated gene therapy to deliver a functional copy of [CRYM](/details-gene/1428) to the affected cells of the inner ear could be a viable long-term strategy. This approach would aim for activation or replacement of function rather than inhibition. However, due to its expression in the brain, any systemic therapeutic intervention would need to be carefully evaluated for potential neurological side effects. Small molecule activators that enhance the enzymatic activity of hypomorphic [CRYM](/details-gene/1428) variants could also be explored as a pharmacological alternative.

Genular Protein ID: 3290859729

Symbol: CRYM_HUMAN

Name: Ketimine reductase mu-crystallin

UniProtKB Accession Codes:

Q14894 D5MNX0 Q5HYB7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 13 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 3 EMBL 13 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 16 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9285773

Title: Two roles for mu-crystallin: a lens structural protein in diurnal marsupials and a possible enzyme in mammalian retinas.

PubMed ID: 9285773

PubMed ID: 9328354

Title: Purification, molecular cloning, and functional expression of the human nicotinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein.

PubMed ID: 9328354

DOI: 10.1210/mend.11.11.9915

PubMed ID: 10493829

Title: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.

PubMed ID: 10493829

DOI: 10.1006/geno.1999.5927

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1384048

Title: Mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase and is expressed in human retina.

PubMed ID: 1384048

DOI: 10.1073/pnas.89.19.9292

PubMed ID: 12471561

Title: Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues.

PubMed ID: 12471561

DOI: 10.1086/345398

PubMed ID: 21332720

Title: Mammalian forebrain ketimine reductase identified as mu-crystallin; potential regulation by thyroid hormones.

PubMed ID: 21332720

DOI: 10.1111/j.1471-4159.2011.07220.x

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 17242435

Title: Crystal structure of human micro-crystallin complexed with NADPH.

PubMed ID: 17242435

DOI: 10.1110/ps.062556907

Sequence Information:

  • Length: 314
  • Mass: 33776
  • Checksum: A49D316B41CE6648
  • Sequence:
    • MSRVPAFLSA AEVEEHLRSS SLLIPPLETA LANFSSGPEG GVMQPVRTVV PVTKHRGYLG 
VMPAYSAAED ALTTKLVTFY EDRGITSVVP SHQATVLLFE PSNGTLLAVM DGNVITAKRT 
AAVSAIATKF LKPPSSEVLC ILGAGVQAYS HYEIFTEQFS FKEVRIWNRT KENAEKFADT 
VQGEVRVCSS VQEAVAGADV IITVTLATEP ILFGEWVKPG AHINAVGASR PDWRELDDEL 
MKEAVLYVDS QEAALKESGD VLLSGAEIFA ELGEVIKGVK PAHCEKTTVF KSLGMAVEDT 
VAAKLIYDSW SSGK