Details for: SHISA9

Gene ID: 729993

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: SHISA9

Ensembl ID: ENSG00000237515

Description: shisa family member 9

Cell Significance Landscape

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 43.17
    rCSI 51.56%
    PRS 95.32
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 42.29
    rCSI 52.61%
    PRS 94.67
  • sncg GABAergic cortical interneuron CL4023015
    CSI 32.7
    rCSI 52.58%
    PRS 95.25
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 30.65
    rCSI 54.13%
    PRS 95.32
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 30.19
    rCSI 50.67%
    PRS 95.62
  • oligodendrocyte precursor cell CL0002453
    CSI 28.31
    rCSI 62.29%
    PRS 90.7
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 24.29
    rCSI 44.14%
    PRS 96.02
  • neuron CL0000540
    CSI 22.72
    rCSI 60.49%
    PRS 92.92
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 22.25
    rCSI 48.27%
    PRS 93.28
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 19.63
    rCSI 47.71%
    PRS 94.12
  • cardiac neuron CL0010022
    CSI 18.69
    rCSI 59.79%
    PRS 98.2
  • Schwann cell CL0002573
    CSI 18.01
    rCSI 51.21%
    PRS 97.33
  • inhibitory interneuron CL0000498
    CSI 17.88
    rCSI 41.28%
    PRS 95.59
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 17.77
    rCSI 42.51%
    PRS 94.26
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 17.41
    rCSI 45.02%
    PRS 98.12
  • ependymal cell CL0000065
    CSI 17.02
    rCSI 34.53%
    PRS 92.01
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 16.33
    rCSI 23.14%
    PRS 98.15
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 15.81
    rCSI 49.45%
    PRS 95.88
  • neural cell CL0002319
    CSI 15.01
    rCSI 56.65%
    PRS 92.93
  • epithelial cell of proximal tubule CL0002306
    CSI 15
    rCSI 36.62%
    PRS 96.05
  • sst GABAergic cortical interneuron CL4023017
    CSI 14.9
    rCSI 19.21%
    PRS 95.95
  • cerebral cortex neuron CL0010012
    CSI 14.64
    rCSI 59.65%
    PRS 95.15
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 14.52
    rCSI 47.73%
    PRS 93.71
  • L6b glutamatergic cortical neuron CL4023038
    CSI 13.29
    rCSI 41.53%
    PRS 95.51
  • interneuron CL0000099
    CSI 13.17
    rCSI 26.44%
    PRS 97.08
  • choroid plexus epithelial cell CL0000706
    CSI 12.5
    rCSI 20.48%
    PRS 96.84
  • glioblast CL0000030
    CSI 12.2
    rCSI 19.46%
    PRS 96.09
  • glutamatergic neuron CL0000679
    CSI 11.54
    rCSI 23.72%
    PRS 93.14
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 11.18
    rCSI 42.27%
    PRS 94.86
  • peripheral nervous system neuron CL2000032
    CSI 10.3
    rCSI 14.03%
    PRS 96.62
  • kidney connecting tubule epithelial cell CL1000768
    CSI 10.1
    rCSI 25.61%
    PRS 97.41
  • cerebral cortex endothelial cell CL1001602
    CSI 10.06
    rCSI 17.4%
    PRS 97.02
  • GABAergic neuron CL0000617
    CSI 9.47
    rCSI 31.71%
    PRS 92.83
  • glial cell CL0000125
    CSI 9.33
    rCSI 35.51%
    PRS 96.06
  • parietal epithelial cell CL1000452
    CSI 8.75
    rCSI 23.38%
    PRS 97.5
  • enteroglial cell CL4040002
    CSI 8.63
    rCSI 45.36%
    PRS 98.26
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.54
    rCSI 50.3%
    PRS 94.99
  • serotonergic neuron CL0000850
    CSI 8.47
    rCSI 37.84%
    PRS 91.56
  • dopaminergic neuron CL0000700
    CSI 7.67
    rCSI 43.32%
    PRS 94.25
  • neural progenitor cell CL0011020
    CSI 7.24
    rCSI 31.86%
    PRS 93.6
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 7.05
    rCSI 60.9%
    PRS 96.64
  • macroglial cell CL0000126
    CSI 6.83
    rCSI 17.56%
    PRS 96.66
  • central nervous system neuron CL2000029
    CSI 6.52
    rCSI 47.93%
    PRS 95.91
  • amacrine cell CL0000561
    CSI 6.44
    rCSI 18.67%
    PRS 95.59
  • medium spiny neuron CL1001474
    CSI 6.13
    rCSI 52.77%
    PRS 95.51
  • glycinergic amacrine cell CL4030028
    CSI 5.47
    rCSI 14.26%
    PRS 95.4
  • Bergmann glial cell CL0000644
    CSI 5.2
    rCSI 7.12%
    PRS 95.84
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.52
    rCSI 7.89%
    PRS 95.36
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.41
    rCSI 12.28%
    PRS 94.51
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 2.56
    rCSI 27.11%
    PRS 97.02
  • retinal ganglion cell CL0000740
    CSI 2.48
    rCSI 5.47%
    PRS 95.21
  • direct pathway medium spiny neuron CL4023026
    CSI 2.09
    rCSI 50.12%
    PRS 93.42
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.07
    rCSI 49.95%
    PRS 93.07
  • cholangiocyte CL1000488
    CSI 1.49
    rCSI 8.93%
    PRS 97.22
  • enteric neuron CL0007011
    CSI 0.34
    rCSI 5.06%
    PRS 98.11

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 [SHISA9](/details-gene/729993) is a protein-coding gene located on chromosome 16p13.12, which encodes the protein shisa-9. Functional annotation strongly implicates [SHISA9](/details-gene/729993) in the regulation of synaptic function within the central nervous system. It is a component of the [postsynaptic density](/details-cell/GO:0014069) and the [AMPA glutamate receptor complex](/details-cell/GO:0032281), where it is involved in modulating [postsynaptic neurotransmitter receptor activity](/details-cell/GO:0098962). Expression data reveals that **Overall**, [SHISA9](/details-gene/729993) is a highly significant marker for specific subtypes of cortical [neurons](/details-cell/CL0000540), particularly GABAergic interneurons, suggesting a specialized role in governing synaptic plasticity and neuronal communication. ## Cellular Roles and Expression Landscape The expression profile of [SHISA9](/details-gene/729993) indicates a highly specialized role within the nervous system. **Overall**, its significance is highest in distinct classes of cortical inhibitory interneurons, including [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 43.17), [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 42.29), and [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 32.70). This strong and specific expression pattern suggests that [SHISA9](/details-gene/729993) is a key component in defining the functional identity of these crucial regulatory [neurons](/details-cell/CL0000540). In addition to its prominence in GABAergic cells, [SHISA9](/details-gene/729993) also shows significant expression in excitatory [neurons](/details-cell/CL0000540), such as [L2/3 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030059). Its role extends to glial cells, with notable significance in [oligodendrocyte precursor cells](/details-cell/CL0002453) and [Schwann cells](/details-cell/CL0002573), hinting at a potential function in neuron-glia communication or glial development. Interestingly, significant expression was also identified in [kidney loop of Henle thin ascending limb epithelial cells](/details-cell/CL1001107), suggesting a previously uncharacterized role for this gene outside of the nervous system. ## Pathways and Molecular Function The molecular functions of [SHISA9](/details-gene/729993) are intrinsically linked to the synapse, which is consistent with its cellular expression profile. Gene Ontology annotations place it within the [postsynaptic density membrane](/details-cell/GO:0098839) and as a component of the [ionotropic glutamate receptor complex](/details-cell/GO:0008328), specifically the [AMPA glutamate receptor complex](/details-cell/GO:0032281). Its involvement in the [regulation of postsynaptic neurotransmitter receptor activity](/details-cell/GO:0098962) and [short-term neuronal synaptic plasticity](/details-cell/GO:0048172) underscores its importance in modulating the strength and efficacy of synaptic transmission. The molecular function of [Pdz domain binding](/details-cell/GO:0030165) suggests that [SHISA9](/details-gene/729993) likely acts as an auxiliary or scaffolding protein, mediating the assembly and localization of receptor complexes at the [glutamatergic synapse](/details-cell/GO:0098978). ## Research Directions The specific expression pattern and annotated functions of [SHISA9](/details-gene/729993) provide a foundation for several compelling research avenues. ### Proposed Hypotheses 1. Given its high expression in multiple GABAergic interneuron subtypes and its role in regulating synaptic plasticity, [SHISA9](/details-gene/729993) may function as a critical modulator of inhibitory synaptic transmission, thereby controlling the excitation-inhibition balance in the cerebral cortex. 2. The significant expression of [SHISA9](/details-gene/729993) in [oligodendrocyte precursor cells (OPCs)](/details-cell/CL0002453), which are known to receive synaptic inputs, suggests that it may play a role in activity-dependent regulation of OPC proliferation, differentiation, or myelination. 3. The unexpected high expression in [kidney loop of Henle thin ascending limb epithelial cells](/details-cell/CL1001107) suggests a novel, non-neuronal function. [SHISA9](/details-gene/729993) might be involved in regulating ion channel localization or cell-cell adhesion in this tissue through its PDZ domain-binding capacity, analogous to its role in the synapse. ### Key Experimental Approach To test the hypothesis that [SHISA9](/details-gene/729993) modulates inhibitory synaptic transmission (Hypothesis 1), a powerful approach would be to use a conditional knockout mouse model. By crossing a [SHISA9](/details-gene/729993)-floxed mouse line with a Cre-driver line specific to a major interneuron class (e.g., Pvalb-Cre or VIP-Cre), one could selectively delete the gene in that cell population. Subsequent ex vivo electrophysiological recordings (whole-cell patch-clamp) from cortical slices would allow for precise measurement of changes in the frequency, amplitude, and kinetics of inhibitory postsynaptic currents (IPSCs) onto pyramidal [neurons](/details-cell/CL0000540). This would directly assess the contribution of [SHISA9](/details-gene/729993) to the function of specific inhibitory circuits. ### Therapeutic Potential The highly specific expression of [SHISA9](/details-gene/729993) in distinct neuronal subtypes, particularly those implicated in maintaining cortical network stability, makes it a potential therapeutic target for neurological and psychiatric disorders characterized by an imbalance of excitation and inhibition, such as epilepsy or schizophrenia. As an auxiliary protein that modulates receptor function, it may be more amenable to pharmacological modulation than the primary receptor subunits themselves. Development of small molecules or biologics that target the PDZ-binding interface of [SHISA9](/details-gene/729993) could offer a novel strategy to either enhance or suppress its modulatory effects on synaptic transmission, depending on the disease pathology. However, targeting the central nervous system presents significant challenges, including the need to cross the blood-brain barrier.

Genular Protein ID: 3049295079

Symbol: SHSA9_HUMAN

Name: Protein shisa-9

UniProtKB Accession Codes:

B4DS77 C9J314 C9JCE9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 10 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 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 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 RNAct 1 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TCDB 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15616553

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

PubMed ID: 15616553

DOI: 10.1038/nature03187

Sequence Information:

  • Length: 424
  • Mass: 46925
  • Checksum: 600FBCEB2846F615
  • Sequence:
    • MRRVLRLLLG CFLTELCARV CRAQERAGHG QLAQLGGVLL LAGGNRSGAA SGEASEGAEA 
SDAPPTRAPT PDFCRGYFDV MGQWDPPFNC SSGDFIFCCG TCGFRFCCTF KKRRLNQSTC 
TNYDTPLWLN TGKPPARKDD PLHDPTKDKT NLIVYIICGV VAVMVLVGIF TKLGLEKAHR 
PQREHMSRAL ADVMRPQGHC NTDHMERDLN IVVHVQHYEN MDTRTPINNL HATQMNNAVP 
TSPLLQQMGH PHSYPNLGQI SNPYEQQPPG KELNKYASLK AVGSSDGDWA VSTLKSPKAD 
KVNDDFYTKR RHLAELAAKG NLPLHPVRVE DEPRAFSPEH GPAKQNGQKS RTNKMPPHPL 
AYTSTTNFKG WDPNEQSLRR QAYSNKGKLG TAETGSSDPL GTRPQHYPPP QPYFITNSKT 
EVTV