Details for: PRDM12

Gene ID: 59335

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: PRDM12

Ensembl ID: ENSG00000130711

Description: PR/SET domain 12

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neural crest cell CL0011012
    CSI 5.7
    rCSI 4.5%
    PRS 99.98

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

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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 [PRDM12](/details-gene/59335) (PR/SET Domain 12) is a protein-coding gene that functions as a critical transcriptional regulator involved in neurogenesis. Located in the nucleus, it possesses DNA-binding and potential methyltransferase activity, enabling it to modulate gene expression, primarily through negative regulation. Its expression is highly specific, with data indicating its primary role is in [neural crest cell](/details-cell/CL0011012) lineages. Functionally, [PRDM12](/details-gene/59335) is essential for the development of pain-sensing neurons (nociceptors), and mutations in this gene are known to cause congenital insensitivity to pain ([Link](https://doi.org/10.1038/ng.3308)). ## Cellular Roles and Expression Landscape The expression profile of [PRDM12](/details-gene/59335) points to a highly specialized function in developmental neurobiology. **Overall**, its most significant expression is identified in the [neural crest cell](/details-cell/CL0011012) (CSI: 5.70), a multipotent embryonic cell population that gives rise to the peripheral nervous system. This specific cellular association is strongly consistent with its established role in the genesis of sensory neurons. The gene's activity in this context suggests it acts as a key fate-determining factor, directing a subset of neural crest progenitors towards a nociceptive lineage. The available data does not highlight significant expression in other cell types, underscoring its specialized role during the formation of the pain-sensing neural circuitry. ## Pathways and Molecular Function The molecular functions of [PRDM12](/details-gene/59335) are centered on its role as a nuclear protein that regulates transcription. It is annotated with DNA binding capabilities ([GO:0003677](https://www.ebi.ac.uk/QuickGO/term/GO:0003677)) and is implicated in the negative regulation of transcription by RNA polymerase II ([GO:0000122](https://www.ebi.ac.uk/QuickGO/term/GO:0000122)). This repressive function is likely mediated through its involvement in protein methylation ([GO:0006479](https://www.ebi.ac.uk/QuickGO/term/GO:0006479)), consistent with its classification as a PR/SET domain-containing protein and its annotated methyltransferase activity ([GO:0008168](https://www.ebi.ac.uk/QuickGO/term/GO:0008168)). These molecular activities are directly linked to critical biological processes. [PRDM12](/details-gene/59335) is a key participant in neurogenesis ([GO:0022008](https://www.ebi.ac.uk/QuickGO/term/GO:0022008)) and neuron projection development ([GO:0031175](https://www.ebi.ac.uk/QuickGO/term/GO:0031175)). Its ultimate physiological importance is highlighted by its involvement in the sensory perception of pain ([GO:0019233](https://www.ebi.ac.uk/QuickGO/term/GO:0019233)) and the detection of temperature stimulus involved in pain perception ([GO:0050965](https://www.ebi.ac.uk/QuickGO/term/GO:0050965)). ## Research Directions The specific role of [PRDM12](/details-gene/59335) as a master regulator of nociceptor development provides a foundation for several targeted research avenues. ### Proposed Hypotheses: 1. **Cell Fate Specification:** [PRDM12](/details-gene/59335) functions as a pioneer factor during embryonic development, binding to chromatin to initiate a repressive program that silences genes associated with alternative [neural crest cell](/details-cell/CL0011012) fates (e.g., glial, melanocyte, or other neuronal subtypes), thereby committing progenitors exclusively to the nociceptive lineage. 2. **Epigenetic Mechanism of Action:** The transcriptional repression mediated by [PRDM12](/details-gene/59335) is dependent on its methyltransferase activity. It directly deposits a specific repressive histone mark (e.g., H3K9me2/3) at the promoters of its target genes, and this enzymatic function is essential for the proper development and function of pain-sensing neurons. ### Key Experimental Approach: To test the hypothesis that [PRDM12](/details-gene/59335) is a critical cell fate specifier (Hypothesis 1), an *in vitro* differentiation model using human pluripotent stem cells (hPSCs) could be employed. A [PRDM12](/details-gene/59335) knockout hPSC line would be generated via CRISPR-Cas9. Both wild-type and knockout cells would then be directed to differentiate through neural crest intermediates into sensory neurons. Single-cell RNA sequencing (scRNA-seq) and ATAC-seq performed at key developmental time points would allow for the mapping of cell trajectories and chromatin accessibility landscapes. This would reveal if the knockout cells fail to generate nociceptors and are shunted towards other neural crest-derived fates, and would identify the direct downstream gene targets of [PRDM12](/details-gene/59335). ### Therapeutic Potential: Given that loss-of-function mutations cause insensitivity to pain, [PRDM12](/details-gene/59335) presents a compelling, albeit challenging, target for the development of novel analgesics for chronic pain conditions. The therapeutic strategy would be **inhibition**, not activation. Developing highly specific small molecule inhibitors targeting the enzymatic SET domain could block the function of [PRDM12](/details-gene/59335). This might prevent the regeneration of damaged nociceptive neurons or modulate their function in chronic pain states. Its highly restricted expression pattern suggests that such an inhibitor could offer a potent, non-opioid analgesic with a potentially favorable side-effect profile.

Genular Protein ID: 2747073828

Symbol: PRD12_HUMAN

Name: PR domain zinc finger protein 12

UniProtKB Accession Codes:

Q9H4Q4 A3KFK9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 14 Gene3D 2 GeneCards 1 GeneReviews 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIRSF 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 26005867

Title: Transcriptional regulator PRDM12 is essential for human pain perception.

PubMed ID: 26005867

DOI: 10.1038/ng.3308

Sequence Information:

  • Length: 367
  • Mass: 40403
  • Checksum: F2C665E3AE076C76
  • Sequence:
    • MMGSVLPAEA LVLKTGLKAP GLALAEVITS DILHSFLYGR WRNVLGEQLF EDKSHHASPK 
TAFTAEVLAQ SFSGEVQKLS SLVLPAEVII AQSSIPGEGL GIFSKTWIKA GTEMGPFTGR 
VIAPEHVDIC KNNNLMWEVF NEDGTVRYFI DASQEDHRSW MTYIKCARNE QEQNLEVVQI 
GTSIFYKAIE MIPPDQELLV WYGNSHNTFL GIPGVPGLEE DQKKNKHEDF HPADSAAGPA 
GRMRCVICHR GFNSRSNLRS HMRIHTLDKP FVCRFCNRRF SQSSTLRNHV RLHTGERPYK 
CQVCQSAYSQ LAGLRAHQKS ARHRPPSTAL QAHSPALPAP HAHAPALAAA AAAAAAAAAH 
HLPAMVL