Details for: NECAB1

Gene ID: 64168

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: NECAB1

Ensembl ID: ENSG00000123119

Description: N-terminal EF-hand calcium binding protein 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 26.04
    rCSI 31.1%
    PRS 97.4
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 24.6
    rCSI 41.29%
    PRS 97.68
  • sncg GABAergic cortical interneuron CL4023015
    CSI 24.29
    rCSI 39.07%
    PRS 97.2
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 21.55
    rCSI 46.75%
    PRS 95.71
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 18.9
    rCSI 45.93%
    PRS 96.52
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 18.48
    rCSI 32.64%
    PRS 97.48
  • choroid plexus epithelial cell CL0000706
    CSI 17.85
    rCSI 29.23%
    PRS 98.07
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 16.49
    rCSI 39.43%
    PRS 96.44
  • neuron CL0000540
    CSI 15.24
    rCSI 40.59%
    PRS 95.56
  • keratocyte CL0002363
    CSI 14.95
    rCSI 35.94%
    PRS 99.34
  • glutamatergic neuron CL0000679
    CSI 14.29
    rCSI 29.36%
    PRS 95.51
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 13.9
    rCSI 45.69%
    PRS 96.03
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 11.71
    rCSI 42.14%
    PRS 96.87
  • inhibitory interneuron CL0000498
    CSI 10.41
    rCSI 24.03%
    PRS 97.48
  • cerebral cortex neuron CL0010012
    CSI 9.89
    rCSI 40.28%
    PRS 97.1
  • retinal pigment epithelial cell CL0002586
    CSI 9.6
    rCSI 19.06%
    PRS 98.45
  • cardiac muscle cell CL0000746
    CSI 9.52
    rCSI 13.65%
    PRS 97.61
  • neural cell CL0002319
    CSI 9.47
    rCSI 35.74%
    PRS 95.59
  • cerebral cortex endothelial cell CL1001602
    CSI 9
    rCSI 15.56%
    PRS 98.31
  • oligodendrocyte CL0000128
    CSI 8.44
    rCSI 24.93%
    PRS 96.9
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 8.42
    rCSI 10.47%
    PRS 97.03
  • vascular leptomeningeal cell CL4023051
    CSI 8.14
    rCSI 14.26%
    PRS 98.45
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 7.66
    rCSI 45.1%
    PRS 96.93
  • pulmonary alveolar type 2 cell CL0002063
    CSI 7.66
    rCSI 11.88%
    PRS 99.18
  • epithelial cell CL0000066
    CSI 6.35
    rCSI 9.75%
    PRS 96.19
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 6.24
    rCSI 8.85%
    PRS 98.95
  • astrocyte of the cerebral cortex CL0002605
    CSI 5.99
    rCSI 13.42%
    PRS 97.53
  • amacrine cell CL0000561
    CSI 5.97
    rCSI 17.31%
    PRS 97.42
  • mesothelial cell CL0000077
    CSI 5.54
    rCSI 21.66%
    PRS 97.07
  • medium spiny neuron CL1001474
    CSI 5.04
    rCSI 43.46%
    PRS 97.34
  • podocyte CL0000653
    CSI 4.98
    rCSI 22.11%
    PRS 99.11
  • parietal epithelial cell CL1000452
    CSI 4.34
    rCSI 11.59%
    PRS 98.64
  • sst GABAergic cortical interneuron CL4023017
    CSI 4.24
    rCSI 5.46%
    PRS 97.73
  • dopaminergic neuron CL0000700
    CSI 4.12
    rCSI 23.31%
    PRS 96.73
  • serotonergic neuron CL0000850
    CSI 3.86
    rCSI 17.22%
    PRS 94.95
  • GABAergic neuron CL0000617
    CSI 3.67
    rCSI 12.3%
    PRS 95.37
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 3.66
    rCSI 11.45%
    PRS 97.69
  • endocardial cell CL0002350
    CSI 3.38
    rCSI 16.18%
    PRS 98.8
  • GABAergic amacrine cell CL4030027
    CSI 3.26
    rCSI 11.16%
    PRS 95.92
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.85
    rCSI 8.92%
    PRS 97.37
  • central nervous system neuron CL2000029
    CSI 2.6
    rCSI 19.14%
    PRS 97.76
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.57
    rCSI 16.05%
    PRS 97.83
  • direct pathway medium spiny neuron CL4023026
    CSI 1.83
    rCSI 43.93%
    PRS 95.88
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.81
    rCSI 43.78%
    PRS 95.8
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.59
    rCSI 5.99%
    PRS 96.91

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 [NECAB1](/details-gene/64168) (N-terminal EF-hand calcium binding protein 1) is a protein-coding gene located on chromosome 8q21.3. As its name suggests, it functions primarily in [calcium ion binding](/details-go/GO:0005509) through its EF-hand domains. Expression data indicate that **Overall**, [NECAB1](/details-gene/64168) is a highly significant marker for specific neuronal populations within the central nervous system. Its expression is particularly prominent in various subtypes of cortical interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), as well as in multiple classes of glutamatergic neurons. This specific expression pattern suggests a crucial role in regulating calcium-dependent signaling pathways that govern neuronal function and communication in the cerebral cortex. ## Cellular Roles and Expression Landscape The expression profile of [NECAB1](/details-gene/64168) highlights its specialized role within the nervous system. The gene shows its highest significance in distinct classes of cortical neurons, suggesting it is a key component of both inhibitory and excitatory circuits. **Overall**, the gene is a defining marker for several GABAergic interneuron subtypes, including: * [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 26.04) * [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 24.60) * [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 24.29) Simultaneously, [NECAB1](/details-gene/64168) is highly expressed in excitatory glutamatergic neurons, particularly those involved in intratelencephalic projections such as [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059) (CSI: 21.55) and [L4 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030063) (CSI: 16.49). This strong and specific expression pattern within the cortex is consistent with early research describing a restricted expression pattern for the NECAB protein family ([Link](https://doi.org/10.1016/s0306-4522(02)00063-5)). Interestingly, significant expression is also noted in some non-neuronal cell types, such as [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 17.85) and [keratocyte](/details-cell/CL0002363) (CSI: 14.95), which may indicate roles in cerebrospinal fluid production and corneal tissue homeostasis, respectively, likely also mediated through calcium-dependent processes. The high specificity for these select cell types suggests that its function is tightly regulated and confined to particular physiological contexts. ## Pathways and Molecular Function The function of [NECAB1](/details-gene/64168) is intrinsically linked to its molecular role as a calcium-binding protein. Gene Ontology annotations confirm its primary [molecular_function](/details-go/GO:0003674) as [calcium ion binding](/details-go/GO:0005509). This activity is fundamental to its involvement in cellular signaling. Cellularly, the protein is localized to the [cytoplasm](/details-go/GO:0005737), [cytosol](/details-go/GO:0005829), and [nucleoplasm](/details-go/GO:0005654), suggesting it may act as a calcium sensor or buffer in multiple cellular compartments, potentially shuttling between them to regulate different processes. Of particular interest is its annotated role in the [biological_process](/details-go/GO:0008150) of [regulation of amyloid precursor protein biosynthetic process](/details-go/GO:0042984). This function connects [NECAB1](/details-gene/64168) to the molecular pathways implicated in Alzheimer's disease, where the processing of amyloid precursor protein is a central pathological event. This is highly relevant given the gene's strong expression in cortical neurons, which are profoundly affected in neurodegenerative disorders. ## Research Directions The specific expression of [NECAB1](/details-gene/64168) in distinct neuronal subtypes and its link to amyloid precursor protein processing present several avenues for future investigation. ### Proposed Hypotheses 1. **Modulation of Interneuron Excitability:** Given its high expression in specific interneuron subtypes ([VIP GABAergic cortical interneuron](/details-cell/CL4023016), [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)), [NECAB1](/details-gene/64168) may function as a key calcium buffer or sensor that fine-tunes their firing properties and synaptic output, thereby shaping cortical network activity and plasticity. 2. **Role in Alzheimer's Disease Pathogenesis:** The annotated function in regulating amyloid precursor protein biosynthesis suggests that dysregulation or loss of [NECAB1](/details-gene/64168) function in glutamatergic and GABAergic neurons could lead to aberrant amyloid-beta production or clearance, contributing to synaptic dysfunction and neurodegeneration in Alzheimer's disease. ### Key Experimental Approach To test the hypothesis that [NECAB1](/details-gene/64168) modulates interneuron excitability, a conditional knockout mouse model could be generated. By crossing a floxed-[NECAB1](/details-gene/64168) mouse with a VIP-Cre driver line, the gene could be selectively deleted in [VIP GABAergic cortical interneuron](/details-cell/CL4023016)s. Subsequent ex-vivo patch-clamp electrophysiology on acute brain slices from these mice would allow for detailed characterization of intrinsic firing properties (e.g., rheobase, firing frequency-current relationship) and synaptic transmission. Changes in these parameters compared to control littermates would provide direct evidence for the role of [NECAB1](/details-gene/64168) in regulating the function of this critical interneuron population. ### Therapeutic Potential As an intracellular calcium-binding protein, [NECAB1](/details-gene/64168) presents a challenging therapeutic target for traditional small molecules or antibodies. However, its potential link to neurodegenerative diseases like Alzheimer's makes it noteworthy. If loss-of-function is shown to be pathogenic, gene therapy approaches aimed at restoring its expression in affected neuronal populations could be a theoretical long-term strategy. Conversely, if its over-activity or mislocalization contributes to calcium dyshomeostasis, strategies like antisense oligonucleotides (ASOs) designed to reduce its expression might be considered. The high neuronal specificity of [NECAB1](/details-gene/64168) is advantageous, as it could minimize off-target effects, but brain-penetrant delivery remains a major obstacle for any therapeutic modality.

Genular Protein ID: 1625214468

Symbol: NECA1_HUMAN

Name: N-terminal EF-hand calcium-binding protein 1

UniProtKB Accession Codes:

Q8N987 Q6NUS7 Q96AZ7 Q9HBW8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 GO 7 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TCDB 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: 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: 12044471

Title: NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual domain structure and a restricted expression pattern.

PubMed ID: 12044471

DOI: 10.1016/s0306-4522(02)00063-5

Sequence Information:

  • Length: 351
  • Mass: 40571
  • Checksum: 74D5E5895B4FECFA
  • Sequence:
    • MEDSQETSPS SNNSSEELSS ALHLSKGMSI FLDILRRADK NDDGKLSFEE FKAYFADGVL 
SGEELHELFH TIDTHNTNNL DTEELCEYFS QHLGEYENVL AALEDLNLSI LKAMGKTKKD 
YQEASNLEQF VTRFLLKETL NQLQSLQNSL ECAMETTEEQ TRQERQGPAK PEVLSIQWPG 
KRSSRRVQRH NSFSPNSPQF NVSGPGLLEE DNQWMTQINR LQKLIDRLEK KDLKLEPPEE 
EIIEGNTKSH IMLVQRQMSV IEEDLEEFQL ALKHYVESAS SQSGCLRISI QKLSNESRYM 
IYEFWENSSV WNSHLQTNYS KTFQRSNVDF LETPELTSTM LVPASWWILN N