Details for: DNAJC12

Gene ID: 56521

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: DNAJC12

Ensembl ID: ENSG00000108176

Description: DnaJ heat shock protein family (Hsp40) member C12

Cell Significance Landscape

Associated with

Significant Cells

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

  • pancreatic A cell CL0000171
    CSI 22.42
    rCSI 23.48%
    PRS 92.67
  • pancreatic D cell CL0000173
    CSI 19.83
    rCSI 19.5%
    PRS 92.58
  • type B pancreatic cell CL0000169
    CSI 12.9
    rCSI 28.57%
    PRS 90.96
  • lung neuroendocrine cell CL1000223
    CSI 9.25
    rCSI 13.68%
    PRS 92.47
  • pancreatic PP cell CL0002275
    CSI 7.63
    rCSI 30.37%
    PRS 93.83
  • pancreatic acinar cell CL0002064
    CSI 7.5
    rCSI 9.97%
    PRS 93.54
  • luminal epithelial cell of mammary gland CL0002326
    CSI 6.18
    rCSI 11.23%
    PRS 95.16
  • type EC enteroendocrine cell CL0000577
    CSI 5.34
    rCSI 18.95%
    PRS 92.05
  • intestine goblet cell CL0019031
    CSI 5.26
    rCSI 4.67%
    PRS 88.65
  • pancreatic epsilon cell CL0005019
    CSI 4.53
    rCSI 21.1%
    PRS 94.18
  • lung ciliated cell CL1000271
    CSI 4.09
    rCSI 4.73%
    PRS 85.69
  • goblet cell CL0000160
    CSI 3.93
    rCSI 3.71%
    PRS 88.84
  • mesodermal cell CL0000222
    CSI 3.93
    rCSI 4.71%
    PRS 89.81
  • enteroendocrine cell of small intestine CL0009006
    CSI 3.91
    rCSI 8.61%
    PRS 93.6
  • neural crest cell CL0011012
    CSI 3.76
    rCSI 2.97%
    PRS 84.23
  • epithelial cell CL0000066
    CSI 3.73
    rCSI 5.74%
    PRS 79.49
  • enteroendocrine cell CL0000164
    CSI 3.53
    rCSI 4.83%
    PRS 89.42
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.42
    rCSI 4.25%
    PRS 76.25
  • peripheral nervous system neuron CL2000032
    CSI 3.26
    rCSI 4.44%
    PRS 84.9
  • cerebellar granule cell CL0001031
    CSI 2.97
    rCSI 4.36%
    PRS 85.98
  • mucus secreting cell CL0000319
    CSI 2.74
    rCSI 4.35%
    PRS 94.92
  • rod bipolar cell CL0000751
    CSI 2.71
    rCSI 4.87%
    PRS 86.26
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.39
    rCSI 4.23%
    PRS 77.84
  • epithelial cell of proximal tubule CL0002306
    CSI 2.36
    rCSI 5.77%
    PRS 84.5
  • OFF-bipolar cell CL0000750
    CSI 2.29
    rCSI 3.13%
    PRS 89.52
  • endocrine cell CL0000163
    CSI 2.18
    rCSI 11.21%
    PRS 96.36
  • hepatocyte CL0000182
    CSI 2.18
    rCSI 3.9%
    PRS 89.42
  • multi-ciliated epithelial cell CL0005012
    CSI 2.09
    rCSI 2.08%
    PRS 85.71
  • retina horizontal cell CL0000745
    CSI 1.95
    rCSI 2.97%
    PRS 87.9
  • tracheobronchial serous cell CL0019001
    CSI 1.78
    rCSI 7.7%
    PRS 93.11
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.75
    rCSI 10.33%
    PRS 78.83
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.6
    rCSI 2.57%
    PRS 79.3
  • type L enteroendocrine cell CL0002279
    CSI 1.56
    rCSI 2.93%
    PRS 92.83
  • amacrine cell CL0000561
    CSI 1.48
    rCSI 4.28%
    PRS 82.91
  • neuroendocrine cell CL0000165
    CSI 1.46
    rCSI 5.64%
    PRS 93.75
  • retinal cone cell CL0000573
    CSI 1.45
    rCSI 2.33%
    PRS 83.42
  • colon goblet cell CL0009039
    CSI 1.37
    rCSI 3.25%
    PRS 92.65
  • enteroendocrine cell of colon CL0009042
    CSI 1.35
    rCSI 6.31%
    PRS 92.98
  • respiratory goblet cell CL0002370
    CSI 1.07
    rCSI 11.69%
    PRS 93.49
  • luminal cell of prostate epithelium CL0002340
    CSI 0.92
    rCSI 4.95%
    PRS 94.43
  • mammary gland epithelial cell CL0002327
    CSI 0.89
    rCSI 3.11%
    PRS 94.57
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.77
    rCSI 2.41%
    PRS 79.69
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.68
    rCSI 2.45%
    PRS 76.39
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.42
    rCSI 2.31%
    PRS 93.29

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.

Comma-separated if multiple.
Comma-separated if multiple.
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)

Loading network (please wait)...

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 [DNAJC12](/details-gene/56521) is a protein-coding gene located on chromosome 10q21.3 that encodes the DnaJ heat shock protein family (Hsp40) member C12. As a co-chaperone, [DNAJC12](/details-gene/56521) is involved in [protein binding](/details-gene/GO:0005515) within the [cytoplasm](/details-gene/GO:0005737) and is known to interact with Hsc70, particularly under conditions of endoplasmic reticulum stress [Link](https://doi.org/10.1007/s12192-013-0471-6). Expression data indicates a highly specialized role for this gene, with significant activity observed in various secretory and endocrine cell types. **Overall**, it is most prominent in [pancreatic A cell](/details-cell/CL0000171), [pancreatic D cell](/details-cell/CL0000173), and [type B pancreatic cell](/details-cell/CL0000169). Clinically, biallelic mutations in [DNAJC12](/details-gene/56521) are causative for a syndrome characterized by hyperphenylalaninemia, dystonia, and intellectual disability, highlighting its critical role in cellular protein homeostasis [Link](https://doi.org/10.1016/j.ajhg.2017.01.002). ## Cellular Roles and Expression Landscape The expression profile of [DNAJC12](/details-gene/56521) strongly suggests a primary function in tissues with high protein synthesis and secretion demands, particularly within the endocrine system. The **Overall** context shows its highest significance in a suite of pancreatic islet cells, including [pancreatic A cell](/details-cell/CL0000171) (CSI: 22.42), [pancreatic D cell](/details-cell/CL0000173) (CSI: 19.83), and [type B pancreatic cell](/details-cell/CL0000169) (CSI: 12.90), which are responsible for producing glucagon, somatostatin, and insulin, respectively. This pattern extends to other pancreatic cell types such as [pancreatic PP cell](/details-cell/CL0002275) and [pancreatic acinar cell](/details-cell/CL0002064). Beyond the pancreas, [DNAJC12](/details-gene/56521) is also a significant marker in other neuroendocrine and secretory epithelial cells. These include [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 9.25), [luminal epithelial cell of mammary gland](/details-cell/CL0002326) (CSI: 6.18), various enteroendocrine cells, and [goblet cell](/details-cell/CL0000160). This consistent enrichment in glandular and hormone-producing cells points to a conserved role in managing the proteostatic stress associated with the synthesis and processing of secreted proteins like hormones and enzymes. ## Pathways and Molecular Function Functionally, [DNAJC12](/details-gene/56521) is annotated as a co-chaperone protein localized to the [cytoplasm](/details-gene/GO:0005737) that participates in [protein binding](/details-gene/GO:0005515). As a member of the DnaJ/Hsp40 family, it functions by interacting with Hsp70-family chaperones to facilitate protein folding, prevent protein aggregation, and manage protein quality control. Research has shown that [DNAJC12](/details-gene/56521) specifically binds to Hsc70 and its expression is upregulated in response to endoplasmic reticulum stress [Link](https://doi.org/10.1007/s12192-013-0471-6). This mechanism is fully consistent with its high expression in secretory cells, which must manage a high flux of proteins through the secretory pathway and are thus sensitive to ER stress. The neurological and metabolic disease caused by its deficiency underscores its non-redundant role in maintaining the function of specific client proteins, such as phenylalanine hydroxylase [Link](https://doi.org/10.1016/j.ajhg.2017.01.002). ## Research Directions The established link between mutations in [DNAJC12](/details-gene/56521) and a severe neuro-metabolic disorder provides a clear foundation for further investigation into its specific cellular functions. Its highly specialized expression pattern in endocrine and neuroendocrine cells suggests that its role extends beyond general "housekeeping" chaperoning and is critical for specific, high-load secretory pathways. **Proposed Hypotheses:** 1. Given its profound expression across all major pancreatic islet cell types, loss-of-function of [DNAJC12](/details-gene/56521) may impair the folding and processing of multiple pro-hormones (e.g., pro-insulin, pro-glucagon, pro-somatostatin), leading to subtle or overt islet cell dysfunction and increased ER stress, potentially contributing to a risk for metabolic diseases. 2. The neurological symptoms (dystonia) associated with [DNAJC12](/details-gene/56521) deficiency, combined with its expression in neuroendocrine cells, suggest that its chaperone activity is essential for the stability and function of multiple enzymes in the monoamine neurotransmitter synthesis pathways, not limited to phenylalanine hydroxylase. **Experimental Approach:** To test the first hypothesis regarding pancreatic function, a targeted knockout of [DNAJC12](/details-gene/56521) could be generated in a human pancreatic beta-cell line (e.g., EndoC-βH1) using CRISPR-Cas9. The resulting knockout cells and isogenic controls would be subjected to glucose stimulation. Key readouts would include quantification of pro-insulin to insulin processing ratios via ELISA or mass spectrometry, measurement of secreted insulin levels, and assessment of cellular viability and ER stress markers (e.g., XBP1 splicing, CHOP expression) under both basal and high-glucose conditions. A defect in insulin processing or secretion and/or an increase in ER stress markers in the knockout cells would support the hypothesis that [DNAJC12](/details-gene/56521) is a critical quality control factor for insulin production. **Therapeutic Potential:** Since the known pathology is a recessive, loss-of-function disorder, the therapeutic strategy would focus on restoring or augmenting [DNAJC12](/details-gene/56521) function rather than inhibition. Gene replacement therapy, delivering a functional copy of the [DNAJC12](/details-gene/56521) gene to affected cell types (e.g., hepatocytes, neurons), represents the most direct and potentially curative approach. Alternatively, the development of small-molecule pharmacological chaperones that could stabilize mutant [DNAJC12](/details-gene/56521) protein or upregulate parallel chaperone pathways might offer another avenue to ameliorate the consequences of its deficiency.

Genular Protein ID: 2432351749

Symbol: DJC12_HUMAN

Name: DnaJ homolog subfamily C member 12

UniProtKB Accession Codes:

Q9UKB3 Q5JVQ1 Q9UKB2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 1 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SMART 1 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: 10760603

Title: Characterization of JDP genes, an evolutionarily conserved J domain-only protein family, from human and moths.

PubMed ID: 10760603

DOI: 10.1016/s0167-4781(00)00047-6

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24122553

Title: The co-chaperone DNAJC12 binds to Hsc70 and is upregulated by endoplasmic reticulum stress.

PubMed ID: 24122553

DOI: 10.1007/s12192-013-0471-6

PubMed ID: 28132689

Title: Biallelic mutations in DNAJC12 cause hyperphenylalaninemia, dystonia, and intellectual disability.

PubMed ID: 28132689

DOI: 10.1016/j.ajhg.2017.01.002

Sequence Information:

  • Length: 198
  • Mass: 23415
  • Checksum: 03429472C61413EB
  • Sequence:
    • MDAILNYRSE DTEDYYTLLG CDELSSVEQI LAEFKVRALE CHPDKHPENP KAVETFQKLQ 
KAKEILTNEE SRARYDHWRR SQMSMPFQQW EALNDSVKTS MHWVVRGKKD LMLEESDKTH 
TTKMENEECN EQRERKKEEL ASTAEKTEQK EPKPLEKSVS PQNSDSSGFA DVNGWHLRFR 
WSKDAPSELL RKFRNYEI