Details for: SEZ6

Gene ID: 124925

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: SEZ6

Ensembl ID: ENSG00000063015

Description: seizure related 6 homolog

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 13.65
    rCSI 29.03%
    PRS 81.65
  • VIP GABAergic cortical interneuron CL4023016
    CSI 8.32
    rCSI 9.94%
    PRS 72.61
  • plasma cell CL0000786
    CSI 5.9
    rCSI 7.73%
    PRS 94.24
  • interneuron CL0000099
    CSI 5.15
    rCSI 10.35%
    PRS 80.18
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 4.62
    rCSI 5.92%
    PRS 83.92
  • sncg GABAergic cortical interneuron CL4023015
    CSI 4.13
    rCSI 6.64%
    PRS 73.59
  • epithelial cell CL0000066
    CSI 3.88
    rCSI 5.96%
    PRS 75.92
  • rod bipolar cell CL0000751
    CSI 3.43
    rCSI 6.16%
    PRS 81.86
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 3.35
    rCSI 10.48%
    PRS 75.88
  • ON-bipolar cell CL0000749
    CSI 3.24
    rCSI 4.81%
    PRS 86.74
  • cerebellar granule cell CL0001031
    CSI 3.17
    rCSI 4.66%
    PRS 81.45
  • inhibitory interneuron CL0000498
    CSI 3.16
    rCSI 7.29%
    PRS 77.3
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.7
    rCSI 3.12%
    PRS 80.06
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.51
    rCSI 9.48%
    PRS 72.76
  • peripheral nervous system neuron CL2000032
    CSI 2.45
    rCSI 3.34%
    PRS 80.5
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.29
    rCSI 2.85%
    PRS 70.26
  • glutamatergic neuron CL0000679
    CSI 2.22
    rCSI 4.57%
    PRS 75.09
  • neural cell CL0002319
    CSI 2.2
    rCSI 8.29%
    PRS 71.58
  • direct pathway medium spiny neuron CL4023026
    CSI 2.07
    rCSI 49.61%
    PRS 70.05
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.07
    rCSI 49.87%
    PRS 70.48
  • melanocyte of skin CL1000458
    CSI 2.07
    rCSI 2.82%
    PRS 56.58
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.05
    rCSI 3.63%
    PRS 71.94
  • GABAergic neuron CL0000617
    CSI 2.04
    rCSI 6.84%
    PRS 72.76
  • retinal bipolar neuron CL0000748
    CSI 1.98
    rCSI 3.71%
    PRS 77.76
  • neural progenitor cell CL0011020
    CSI 1.98
    rCSI 8.71%
    PRS 76.16
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.98
    rCSI 7.12%
    PRS 70.48
  • central nervous system neuron CL2000029
    CSI 1.8
    rCSI 13.2%
    PRS 77.23
  • retina horizontal cell CL0000745
    CSI 1.78
    rCSI 2.71%
    PRS 84.49
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.76
    rCSI 4.28%
    PRS 70.25
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.66
    rCSI 5.18%
    PRS 73.87
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.37
    rCSI 2.3%
    PRS 72.45
  • medium spiny neuron CL1001474
    CSI 1.18
    rCSI 10.15%
    PRS 77.91
  • retinal cone cell CL0000573
    CSI 1.01
    rCSI 1.63%
    PRS 78.96
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.01
    rCSI 5.94%
    PRS 72.91
  • dopaminergic neuron CL0000700
    CSI 0.89
    rCSI 5.02%
    PRS 75.64
  • GABAergic amacrine cell CL4030027
    CSI 0.89
    rCSI 3.03%
    PRS 74.17
  • retinal ganglion cell CL0000740
    CSI 0.86
    rCSI 1.89%
    PRS 75.4

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 [SEZ6](/details-gene/124925) (seizure related 6 homolog) is a protein-coding gene located on chromosome 17q11.2 in humans. It encodes a protein primarily involved in neuronal development and synaptic function. Functional annotations link [SEZ6](/details-gene/124925) to processes such as dendrite development, synapse maturation, and the regulation of excitatory postsynaptic potentials. **Overall**, expression data reveals its profound significance in the nervous system, with its highest expression observed in neural [progenitor cell](/details-cell/CL0011026)s and a wide variety of interneurons. Notably, mutations in this gene have been associated with febrile seizures, highlighting its clinical relevance in maintaining neurological homeostasis ([Link](https://doi.org/10.1002/jnr.21103)). ## Cellular Roles and Expression Landscape The expression profile of [SEZ6](/details-gene/124925) firmly establishes its role as a key gene within the central nervous system. Its highest significance is observed in [progenitor cell](/details-cell/CL0011026) (CSI: 13.65) and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s (CSI: 4.62), suggesting a crucial function during the early stages of neural differentiation and development. Beyond its role in neurogenesis, [SEZ6](/details-gene/124925) is a prominent marker across multiple, functionally distinct neuronal subtypes. It shows high significance in various inhibitory interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 8.32), [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 4.13), and [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036) (CSI: 3.35). This suggests a broad role in shaping cortical inhibitory circuits. Its expression is also significant in other neuronal populations such as [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012)s, [cerebellar granule cell](/details-cell/CL0001031)s, and retinal cells like the [rod bipolar cell](/details-cell/CL0000751), underscoring its widespread importance in neuronal function across different brain regions. Interestingly, the data also indicate a significant expression level in [plasma cell](/details-cell/CL0000786)s (CSI: 5.90), a mature B lymphocyte lineage. This finding is notable given the overwhelming neural context of [SEZ6](/details-gene/124925) and may point towards a less-characterized role in the immune system or in neuro-immune interactions. ## Pathways and Molecular Function The functions of [SEZ6](/details-gene/124925) are tightly linked to the structural and electrical properties of neurons. Gene Ontology annotations place the protein product in cellular components critical for synaptic communication, including the [apical dendrite](/details-cell/GO:0097440), [dendritic shaft](/details-cell/GO:0043198), and [dendritic spine](/details-cell/GO:0043197). This localization is consistent with its annotated biological processes, which include [regulation of dendrite development](/details-cell/GO:0050773) and [synapse maturation](/details-cell/GO:0060074). Functionally, [SEZ6](/details-gene/124925) is implicated in modulating synaptic signaling, as evidenced by its role in [excitatory postsynaptic potential](/details-cell/GO:0060079) and the [regulation of protein kinase c signaling](/details-cell/GO:0090036). This molecular activity likely underpins its contribution to higher-order processes like [adult locomotory behavior](/details-cell/GO:0008344). Its involvement in [cerebellar purkinje cell layer development](/details-cell/GO:0021680) is consistent with its expression in related cell types like the [cerebellar granule cell](/details-cell/CL0001031), further reinforcing its importance in neural circuit assembly. ## Research Directions The available data position [SEZ6](/details-gene/124925) as a critical regulator of neuronal development and synaptic function, with its dysregulation linked to seizure disorders. This provides a clear basis for further investigation. **Proposed Hypotheses:** 1. Given its high significance in [progenitor cell](/details-cell/CL0011026)s and its role in dendrite development, loss-of-function mutations in [SEZ6](/details-gene/124925) may impair the proper migration and integration of neurons during corticogenesis. This could lead to the formation of aberrant microcircuits that are inherently hyperexcitable, predisposing an individual to seizures. 2. The gene's role in modulating excitatory postsynaptic potentials suggests it is a key component of homeostatic synaptic plasticity. It is hypothesized that [SEZ6](/details-gene/124925) acts as a brake on synaptic strengthening, and its absence or dysfunction leads to runaway excitation in vulnerable circuits, which manifests clinically as seizures. 3. The unexpected high expression in [plasma cell](/details-cell/CL0000786)s suggests a potential neuro-immune axis. It is hypothesized that [SEZ6](/details-gene/124925) may be involved in a shared signaling pathway for cell maturation or that plasma cells expressing SEZ6 could potentially interact with the nervous system, although the mechanism remains entirely speculative. **Key Experimental Approach:** To test the hypothesis that [SEZ6](/details-gene/124925) is critical for controlling synaptic excitation (Hypothesis 2), a robust experimental plan would involve genetic manipulation in a relevant model system. Using CRISPR-Cas9 to generate a conditional knockout of [SEZ6](/details-gene/124925) in mouse cortical neurons would be a definitive approach. Electrophysiological recordings (whole-cell patch-clamp) from these knockout neurons could then be used to measure miniature excitatory postsynaptic currents (mEPSCs) and evoked synaptic responses. An increase in mEPSC amplitude or frequency, or a lower threshold for inducing long-term potentiation (LTP), would provide strong evidence that [SEZ6](/details-gene/124925) normally functions to constrain synaptic strength. **Therapeutic Potential:** As loss-of-function mutations in [SEZ6](/details-gene/124925) are associated with febrile seizures, a logical therapeutic strategy would aim at **activation** or functional restoration of the SEZ6 pathway, rather than inhibition. This could potentially be achieved through small-molecule agonists that enhance SEZ6 signaling or, in the long term, through gene therapy approaches designed to restore its expression in affected neuronal populations. However, its broad expression across many neuron types presents a significant challenge for targeted therapy, as off-target effects could be substantial. Therefore, any therapeutic development would require a precise understanding of its role in the specific cell types and circuits that initiate seizures.

Genular Protein ID: 1464141785

Symbol: SEZ6_HUMAN

Name: Seizure protein 6 homolog

UniProtKB Accession Codes:

Q53EL9 B6ZDN1 Q8N701 Q8NB57 Q8ND50 Q8TD25 Q96NI5 Q96NQ3

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 ExpressionAtlas 1 GO 13 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 3 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 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: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

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: 23234360

Title: LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins.

PubMed ID: 23234360

DOI: 10.1021/pr300963h

PubMed ID: 17086543

Title: Febrile seizures are associated with mutation of seizure-related (SEZ) 6, a brain-specific gene.

PubMed ID: 17086543

DOI: 10.1002/jnr.21103

Sequence Information:

  • Length: 994
  • Mass: 107425
  • Checksum: BF715A8EEA4101C6
  • Sequence:
    • MRPVALLLLP SLLALLAHGL SLEAPTVGKG QAPGIEETDG ELTAAPTPEQ PERGVHFVTT 
APTLKLLNHH PLLEEFLQEG LEKGDEELRP ALPFQPDPPA PFTPSPLPRL ANQDSRPVFT 
SPTPAMAAVP TQPQSKEGPW SPESESPMLR ITAPLPPGPS MAVPTLGPGE IASTTPPSRA 
WTPTQEGPGD MGRPWVAEVV SQGAGIGIQG TITSSTASGD DEETTTTTTI ITTTITTVQT 
PGPCSWNFSG PEGSLDSPTD LSSPTDVGLD CFFYISVYPG YGVEIKVQNI SLREGETVTV 
EGLGGPDPLP LANQSFLLRG QVIRSPTHQA ALRFQSLPPP AGPGTFHFHY QAYLLSCHFP 
RRPAYGDVTV TSLHPGGSAR FHCATGYQLK GARHLTCLNA TQPFWDSKEP VCIAACGGVI 
RNATTGRIVS PGFPGNYSNN LTCHWLLEAP EGQRLHLHFE KVSLAEDDDR LIIRNGDNVE 
APPVYDSYEV EYLPIEGLLS SGKHFFVELS TDSSGAAAGM ALRYEAFQQG HCYEPFVKYG 
NFSSSTPTYP VGTTVEFSCD PGYTLEQGSI IIECVDPHDP QWNETEPACR AVCSGEITDS 
AGVVLSPNWP EPYGRGQDCI WGVHVEEDKR IMLDIRVLRI GPGDVLTFYD GDDLTARVLG 
QYSGPRSHFK LFTSMADVTI QFQSDPGTSV LGYQQGFVIH FFEVPRNDTC PELPEIPNGW 
KSPSQPELVH GTVVTYQCYP GYQVVGSSVL MCQWDLTWSE DLPSCQRVTS CHDPGDVEHS 
RRLISSPKFP VGATVQYICD QGFVLMGSSI LTCHDRQAGS PKWSDRAPKC LLEQLKPCHG 
LSAPENGARS PEKQLHPAGA TIHFSCAPGY VLKGQASIKC VPGHPSHWSD PPPICRAASL 
DGFYNSRSLD VAKAPAASST LDAAHIAAAI FLPLVAMVLL VGGVYFYFSR LQGKSSLQLP 
RPRPRPYNRI TIESAFDNPT YETGSLSFAG DERI