Details for: PRR12

Gene ID: 57479

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: PRR12

Ensembl ID: ENSG00000126464

Description: proline rich 12

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of proximal tubule CL0002306
    CSI 4.08
    rCSI 9.97%
    PRS 88.3
  • naive B cell CL0000788
    CSI 4.03
    rCSI 3.45%
    PRS 95.85
  • interneuron CL0000099
    CSI 3.65
    rCSI 7.34%
    PRS 88.66
  • neural crest cell CL0011012
    CSI 3.52
    rCSI 2.78%
    PRS 87.89
  • ependymal cell CL0000065
    CSI 3.39
    rCSI 6.89%
    PRS 78.45
  • secretory cell CL0000151
    CSI 3.23
    rCSI 3.37%
    PRS 92.47
  • mature T cell CL0002419
    CSI 3.22
    rCSI 2.51%
    PRS 98.17
  • lung ciliated cell CL1000271
    CSI 3.22
    rCSI 3.72%
    PRS 88.95
  • melanocyte CL0000148
    CSI 3.14
    rCSI 2.33%
    PRS 90.89
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3
    rCSI 3.58%
    PRS 83.26
  • choroid plexus epithelial cell CL0000706
    CSI 2.8
    rCSI 4.58%
    PRS 87.87
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.72
    rCSI 7.1%
    PRS 94.81
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.71
    rCSI 3.84%
    PRS 92.04
  • stem cell CL0000034
    CSI 2.54
    rCSI 2.45%
    PRS 90.32
  • alpha-beta T cell CL0000789
    CSI 2.53
    rCSI 2.96%
    PRS 97.99
  • cerebral cortex endothelial cell CL1001602
    CSI 2.27
    rCSI 3.92%
    PRS 89.31
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.24
    rCSI 2.78%
    PRS 81.08
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.16
    rCSI 5.48%
    PRS 89.02
  • mononuclear phagocyte CL0000113
    CSI 2.03
    rCSI 4.47%
    PRS 95.46
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.03
    rCSI 4.55%
    PRS 83.51
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.99
    rCSI 2.56%
    PRS 84.2
  • chondrocyte CL0000138
    CSI 1.85
    rCSI 2.94%
    PRS 89.75
  • cardiac muscle cell CL0000746
    CSI 1.81
    rCSI 2.6%
    PRS 86.56
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.7
    rCSI 3.01%
    PRS 82.57
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.68
    rCSI 2.82%
    PRS 83.27
  • renal interstitial pericyte CL1001318
    CSI 1.57
    rCSI 4.32%
    PRS 91.64
  • parietal epithelial cell CL1000452
    CSI 1.44
    rCSI 3.85%
    PRS 89.49
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.38
    rCSI 2.21%
    PRS 84.23
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.94
    rCSI 2.28%
    PRS 81.1
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.78
    rCSI 2.45%
    PRS 84.27
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.65
    rCSI 2.47%
    PRS 83.37
  • blood vessel smooth muscle cell CL0019018
    CSI 0.63
    rCSI 5.13%
    PRS 91.94
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.53
    rCSI 1.89%
    PRS 81.44
  • central nervous system neuron CL2000029
    CSI 0.46
    rCSI 3.42%
    PRS 87.13

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)

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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 [PRR12](/details-gene/57479), or Proline Rich 12, is a protein-coding gene located on chromosome 19q13.33. Gene Ontology annotations suggest its protein product localizes to the [nucleus](/details-cell/GO:0005634) as well as neuronal structures such as the [neuron projection](/details-cell/GO:0043005) and [postsynaptic density](/details-cell/GO:0014069). Consistent with a role in the nervous system, loss-of-function mutations in [PRR12](/details-gene/57479) are associated with neurodevelopmental disorders characterized by intellectual disability and complex eye abnormalities, including microphthalmia ([Link](https://doi.org/10.1007/s00439-018-1877-0), [Link](https://doi.org/10.1111/cge.13897)). Expression data reveals a broad but significant presence across diverse cell lineages, including high significance in various neuronal subtypes, immune cells such as [naive B cells](/details-cell/CL0000788), and epithelial cells, particularly those of the kidney proximal tubule. This widespread expression pattern, coupled with its identification in multiple phosphoproteomic studies, suggests [PRR12](/details-gene/57479) may function as a widely utilized signaling node involved in fundamental cellular processes. ## Cellular Roles and Expression Landscape The expression profile of [PRR12](/details-gene/57479) is notable for its breadth, indicating a functional role in multiple, distinct biological systems rather than serving as a marker for a single cell lineage. **Overall**, the gene shows high significance in several key areas: * **Nervous System:** A prominent role in the nervous system is strongly suggested by its high significance in multiple neural cell types, including [interneurons](/details-cell/CL0000099) (CSI: 3.65), [ependymal cells](/details-cell/CL0000065) (CSI: 3.39), [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 3.00), and [choroid plexus epithelial cells](/details-cell/CL0000706) (CSI: 2.80). This is consistent with the neurodevelopmental phenotypes observed in patients with [PRR12](/details-gene/57479) mutations. * **Epithelial Tissues:** The highest overall significance is observed in [epithelial cells of the proximal tubule](/details-cell/CL0002306) (CSI: 4.08) in the kidney. It is also significant in other epithelial populations like [lung ciliated cells](/details-cell/CL1000271) (CSI: 3.22) and [kidney loop of Henle thin descending limb epithelial cells](/details-cell/CL1001111) (CSI: 2.71), suggesting a potential role in epithelial cell function or maintenance. * **Immune System:** [PRR12](/details-gene/57479) is a significant gene in several immune cell populations, including [naive B cells](/details-cell/CL0000788) (CSI: 4.03), [mature T cells](/details-cell/CL0002419) (CSI: 3.22), and [kidney interstitial alternatively activated macrophages](/details-cell/CL1000695) (CSI: 2.72). Its identification in a study of T cell receptor signaling further supports a functional role in lymphocyte biology ([Link](https://doi.org/10.1126/scisignal.2000007)). * **Developmental Context:** The gene's significance in [neural crest cells](/details-cell/CL0011012) (CSI: 3.52) and [stem cells](/details-cell/CL0000034) (CSI: 2.54) aligns well with its established role in development, as defects in these precursor populations could plausibly lead to the congenital abnormalities reported in patients. ## Pathways and Molecular Function Functional annotations indicate that the [PRR12](/details-gene/57479) protein is associated with both nuclear and neuronal compartments. Its localization to the [nucleus](/details-cell/GO:0005634) suggests a potential role in transcriptional regulation or chromatin dynamics, which could explain its broad impact on the development of multiple organ systems. Concurrently, its presence in [neuron projections](/details-cell/GO:0043005) and specifically at the [postsynaptic density](/details-cell/GO:0014069) points to a more direct function in synaptic transmission and plasticity. This dual localization is consistent with the intellectual disability phenotype associated with its mutation, which likely arises from defects in neural circuit formation and function. Furthermore, [PRR12](/details-gene/57479) has been repeatedly identified as a phosphoprotein in large-scale proteomics studies ([Link](https://doi.org/10.1016/j.cell.2006.09.026), [Link](https://doi.org/10.1073/pnas.0805139105)). This suggests its activity is dynamically regulated by intracellular signaling cascades. Its phosphorylation has been observed in contexts such as T cell receptor signaling ([Link](https://doi.org/10.1126/scisignal.2000007)) and mitosis ([Link](https://doi.org/10.1126/scisignal.2000475)), hinting that it may integrate signals related to cell cycle progression and immune activation to control downstream cellular events. ## Research Directions The broad expression pattern of [PRR12](/details-gene/57479) and its link to specific developmental disorders present several avenues for future research. The key challenge is to dissect its fundamental cellular function and understand how its disruption leads to tissue-specific pathology. **Proposed Hypotheses:** 1. Given its nuclear localization and the severe neurodevelopmental consequences of its mutation, [PRR12](/details-gene/57479) may function as a transcriptional co-regulator or chromatin-associated protein that is essential for the proper differentiation of neuronal progenitors, particularly those derived from [neural crest cells](/details-cell/CL0011012). Haploinsufficiency of [PRR12](/details-gene/57479) could disrupt the gene expression programs required for craniofacial and ocular development, leading to microphthalmia. 2. The dual localization to the synapse and nucleus in neurons suggests [PRR12](/details-gene/57479) may act as a bridge between synaptic activity and gene expression. We hypothesize that synaptic signaling triggers the phosphorylation and potential translocation of [PRR12](/details-gene/57479), which in turn modulates the transcription of genes necessary for synaptic plasticity and memory formation in cells like cortical [interneurons](/details-cell/CL0000099). **Key Experimental Approach:** To test the first hypothesis regarding its role in neurodevelopment, a powerful approach would be to use patient-derived induced pluripotent stem cells (iPSCs) carrying a heterozygous loss-of-function mutation in [PRR12](/details-gene/57479). * **Experiment:** These iPSCs, alongside isogenic corrected controls, could be differentiated in vitro into [neural crest cells](/details-cell/CL0011012) and subsequently into relevant derivatives like craniofacial neurons and melanocytes. * **Analysis:** A combination of single-cell RNA-seq and ATAC-seq would be performed at key differentiation time points to map the transcriptional and chromatin accessibility changes caused by [PRR12](/details-gene/57479) haploinsufficiency. This would identify the specific developmental pathways and target genes that are dysregulated, providing a direct molecular link between the mutation and the observed clinical phenotype. **Therapeutic Potential:** As the pathology associated with [PRR12](/details-gene/57479) appears to stem from haploinsufficiency and loss of function, it is not a suitable target for therapeutic inhibition. The primary challenge is the restoration of protein function, especially in the context of a congenital neurodevelopmental disorder where critical events occur in utero. Future therapeutic strategies, though highly challenging, might involve gene replacement therapies or the development of small molecules that could stabilize the remaining wild-type PRR12 protein or enhance its expression. However, its widespread expression profile suggests that systemic interventions would need to be carefully evaluated for off-target effects in tissues like the immune system and kidney.

Genular Protein ID: 2652801653

Symbol: PRR12_HUMAN

Name: Proline-rich protein 12

UniProtKB Accession Codes:

Q9ULL5 E9PB06 Q8N4J6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 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 PRO 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 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 10574462

Title: Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10574462

DOI: 10.1093/dnares/6.5.337

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: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 29556724

Title: De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities.

PubMed ID: 29556724

DOI: 10.1007/s00439-018-1877-0

PubMed ID: 33314030

Title: Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia.

PubMed ID: 33314030

DOI: 10.1111/cge.13897

PubMed ID: 33824499

Title: Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities.

PubMed ID: 33824499

DOI: 10.1038/s41436-021-01129-6

Sequence Information:

  • Length: 2036
  • Mass: 211044
  • Checksum: 11D30279770ECFF0
  • Sequence:
    • MDRNYPSAGF GDPLGAGAGW SYERSAKASL VYGSSRTSHP ETDILHRQAY AAPHPLQSYA 
TNHHPAGLSG LFDTGLHHAG SAGPDASVMN LISALESRGP QPGPSASSLL SQFRSPSWQT 
AMHTPGPTEL FISGALPGSS TFPSSSALSA YQHPASFGSR PFPVPSSLSL QDPPFSPPAN 
GLLSPHDVLH LKPSQAPTVP SSLGFERLAG GGVLGPAGLG PAQTPPYRPG PPDPPPPPRH 
LPTQFNLLAS SSAAAAAAEQ SSPQLYNFSG AAPGPPPPER ALPRQDTVIK HYQRPASAQP 
PPPPPPAHAL QHYLSCGGSY PSMGHRANLA CSPLGGGEPS PGAGEPSKAG PSGATAGASG 
RATGPEAAGG GGAGGGGGGY RPIIQSPGYK TGKGGYGAAA GGATRPPPPR STATPKCQSL 
GGPAAAYATG KASGAGGAGG QAYSPGQPQG LLGPQAYGQG FGGGQAQDLS KAPSYSGGPP 
QPPSGPPPPG LATCQSYSPD QLQGQLYGVQ GEPYPGPAAH SQGLPTASPS LSYSTGHSPA 
LSGHGGGWGP SSLGGGGEAS PSHIIRPLQS PPATGRPPGV GSPGAPGKYL SSVLASAPFL 
APPGAGSYAA GAGGYKGKGD GSELLAGPGG PPAERTEDEE FLIQHLLQAP SPPRTSGADG 
LVGEDGAADA SKGLGGSGGA GGPPGTPYEL AKEDPQRYHL QSVIRTSASL DEGATAALEL 
GLGRLKEKKK GPERGGETPE GLATSVVHYG AGAKELGAFL QKSPPPPPPT AQSTQPTPHG 
LLLEAGGPDL PLVLPPPPPQ LLPSVLSHAP SPSPSASKVG VHLLEPATRD GAPQPPPPPP 
PPPPPMPLQL EAHLRSHGLE PAAPSPRLRP EESLDPPGAM QELLGALEPL PPAPGDTGVG 
PPNSEGKDPA GAYRSPSPQG TKAPRFVPLT SICFPDSLLQ DEERSFFPTM EEMFGGGAAD 
DYGKAGPPED EGDPKAGAGP PPGPPAYDPY GPYCPGRASG AGPETPGLGL DPNKPPELPS 
TVNAEPLGLI QSGPHQAAPP PPPPPPPPPA PASEPKGGLT SPIFCSTKPK KLLKTSSFHL 
LRRRDPPFQT PKKLYAQEYE FEADEDKADV PADIRLNPRR LPDLVSSCRS RPALSPLGDI 
DFCPPNPGPD GPRRRGRKPT KAKRDGPPRP RGRPRIRPLE VPTTAGPASA STPTDGAKKP 
RGRGRGRGRK AEEAGGTRLE PLKPLKIKLS VPKAGEGLGT SSGDAISGTD HNSLDSSLTR 
EKIEAKIKEV EEKQPEMKSG FMASFLDFLK SGKRHPPLYQ AGLTPPLSPP KSVPPSVPAR 
GLQPQPPATP AVPHPPPSGA FGLGGALEAA ESEGLGLGCP SPCKRLDEEL KRNLETLPSF 
SSDEEDSVAK NRDLQESISS AISALDDPPL AGPKDTSTPD GPPLAPAAAV PGPPPLPGLP 
SANSNGTPEP PLLEEKPPPT PPPAPTPQPQ PPPPPPPPQP ALPSPPPLVA PTPSSPPPPP 
LPPPPPPAMP SPPPPPPPAA APLAAPPEEP AAPSPEDPEL PDTRPLHLAK KQETAAVCGE 
TDEEAGESGG EGIFRERDEF VIRAEDIPSL KLALQTGREP PPIWRVQKAL LQKFTPEIKD 
GQRQFCATSN YLGYFGDAKN RYQRLYVKFL ENVNKKDYVR VCARKPWHRP PVPVRRSGQA 
KNPVSAGGSS APPPKAPAPP PKPETPEKTT SEKPPEQTPE TAMPEPPAPE KPSLLRPVEK 
EKEKEKVTRG ERPLRGERAT SGRQTRPERS LATGQPATSR LPKARPTKVK AEPPPKKRKK 
WLKEAGGNAT AGGGPPGSSS DSESSPGAPS EDERAVPGRL LKTRAMREMY RSYVEMLVST 
ALDPDMIQAL EDTHDELYLP PMRKIDGLLN EHKKKVLKRL SLSPALQDAL HTFPQLQVEQ 
SGEGSPEEGA VRLRPAGEPY NRKTLSKLKR SVVRAQEFKV ELEKSGYYTL YHSLHHYKYH 
TFLRCRDQTL AIEGGAEDLG QEEVVQQCMR NQPWLEQLFD SFSDLLAQAQ AHSRCG