Details for: IGSF21

Gene ID: 84966

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: IGSF21

Ensembl ID: ENSG00000117154

Description: immunoglobin superfamily member 21

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Adherens junction
    (GO:0005912)
  • External side of plasma membrane
    (GO:0009897)
  • Heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
    (GO:0007157)
  • Homophilic cell adhesion via plasma membrane adhesion molecules
    (GO:0007156)
  • Inhibitory synapse
    (GO:0060077)
  • Postsynaptic density membrane
    (GO:0098839)
  • Presynaptic membrane
    (GO:0042734)
  • Synapse maturation
    (GO:0060074)
  • Trans-synaptic signaling, modulating synaptic transmission
    (GO:0099550)

Significant Cells

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

  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 22.32
    rCSI 40.55%
    PRS 92.5
  • OFF-bipolar cell CL0000750
    CSI 21.27
    rCSI 29.09%
    PRS 94.48
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 17.91
    rCSI 43.52%
    PRS 87.59
  • L6b glutamatergic cortical neuron CL4023038
    CSI 17.27
    rCSI 53.98%
    PRS 90.04
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 15.61
    rCSI 56.16%
    PRS 87.82
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 15.15
    rCSI 19.44%
    PRS 93.94
  • interneuron CL0000099
    CSI 12.22
    rCSI 24.53%
    PRS 93.31
  • VIP GABAergic cortical interneuron CL4023016
    CSI 12.06
    rCSI 14.41%
    PRS 89.33
  • inhibitory interneuron CL0000498
    CSI 11.91
    rCSI 27.5%
    PRS 90.83
  • retinal bipolar neuron CL0000748
    CSI 11.84
    rCSI 22.17%
    PRS 91.39
  • Kupffer cell CL0000091
    CSI 11.45
    rCSI 26.19%
    PRS 96.81
  • rod bipolar cell CL0000751
    CSI 11.1
    rCSI 19.95%
    PRS 93.17
  • cerebral cortex neuron CL0010012
    CSI 10.7
    rCSI 43.58%
    PRS 90.93
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.91
    rCSI 52.48%
    PRS 89.58
  • dopaminergic neuron CL0000700
    CSI 8.75
    rCSI 49.47%
    PRS 89.37
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 8.48
    rCSI 22.1%
    PRS 97.32
  • OFFx cell CL4033036
    CSI 8.32
    rCSI 39.14%
    PRS 88.21
  • oligodendrocyte precursor cell CL0002453
    CSI 8.28
    rCSI 18.22%
    PRS 83.7
  • diffuse bipolar 3a cell CL4033029
    CSI 8.24
    rCSI 56.09%
    PRS 90.28
  • sst GABAergic cortical interneuron CL4023017
    CSI 8.2
    rCSI 10.57%
    PRS 90.07
  • ON-bipolar cell CL0000749
    CSI 8.15
    rCSI 12.11%
    PRS 94.97
  • tuft cell of colon CL0009041
    CSI 8.1
    rCSI 18.87%
    PRS 96.31
  • invaginating midget bipolar cell CL4033034
    CSI 7.79
    rCSI 45.98%
    PRS 89.83
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 7.7
    rCSI 9.58%
    PRS 87.62
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 7.25
    rCSI 12.81%
    PRS 88.99
  • central nervous system macrophage CL0000878
    CSI 7.2
    rCSI 23.87%
    PRS 96.66
  • diffuse bipolar 1 cell CL4033027
    CSI 7
    rCSI 52.62%
    PRS 88.21
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 6.96
    rCSI 22.87%
    PRS 88.42
  • diffuse bipolar 3b cell CL4033030
    CSI 6.95
    rCSI 46.16%
    PRS 91.63
  • vascular leptomeningeal cell CL4023051
    CSI 6.38
    rCSI 11.19%
    PRS 94.43
  • diffuse bipolar 6 cell CL4033032
    CSI 6.2
    rCSI 32.62%
    PRS 89.07
  • flat midget bipolar cell CL4033033
    CSI 6.09
    rCSI 43.56%
    PRS 89.26
  • mononuclear phagocyte CL0000113
    CSI 5.85
    rCSI 12.88%
    PRS 97.6
  • microglial cell CL0000129
    CSI 5.67
    rCSI 22.84%
    PRS 94.9
  • cerebellar granule cell CL0001031
    CSI 5.52
    rCSI 8.11%
    PRS 93.06
  • diffuse bipolar 2 cell CL4033028
    CSI 4.9
    rCSI 37.97%
    PRS 90.5
  • neural cell CL0002319
    CSI 4.6
    rCSI 17.36%
    PRS 86.86
  • cerebellar neuron CL1001611
    CSI 4.19
    rCSI 36.91%
    PRS 87.93
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 3.86
    rCSI 8.37%
    PRS 88.22
  • mature microglial cell CL0002629
    CSI 3.83
    rCSI 15.9%
    PRS 94.48
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.78
    rCSI 6.08%
    PRS 89.91
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 3.59
    rCSI 13.57%
    PRS 89.29
  • glutamatergic neuron CL0000679
    CSI 3.57
    rCSI 7.33%
    PRS 88.05
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 3.43
    rCSI 8.19%
    PRS 89.51
  • serotonergic neuron CL0000850
    CSI 3
    rCSI 13.38%
    PRS 85.98
  • GABAergic neuron CL0000617
    CSI 2.73
    rCSI 9.15%
    PRS 87.43
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.75
    rCSI 2.93%
    PRS 89.31
  • central nervous system neuron CL2000029
    CSI 1.67
    rCSI 12.31%
    PRS 91.56
  • retinal cone cell CL0000573
    CSI 1.4
    rCSI 2.26%
    PRS 90.99
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.29
    rCSI 4.05%
    PRS 91.21
  • cone retinal bipolar cell CL0000752
    CSI 1.06
    rCSI 13.83%
    PRS 92.92
  • diffuse bipolar 4 cell CL4033031
    CSI 0.73
    rCSI 8.36%
    PRS 85.68
  • GABAergic interneuron CL0011005
    CSI 0.52
    rCSI 8.17%
    PRS 95.74

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 [IGSF21](/details-gene/84966) is a protein-coding gene located on human chromosome 1 that encodes Immunoglobulin Superfamily Member 21, a cell adhesion molecule. Its initial characterization emerged from large-scale cDNA and genome sequencing projects ([Link](https://doi.org/10.1038/nature04727), [Link](https://doi.org/10.1101/gr.2596504)). Functional annotations strongly point to a role in both homophilic and heterophilic cell-cell adhesion, with a particular enrichment in synaptic structures. This is consistent with its expression profile, which shows high and specific significance in numerous cell types of the central nervous system, including oligodendrocyte precursors and a wide array of glutamatergic and GABAergic neurons. The data collectively suggest that [IGSF21](/details-gene/84966) is a key molecular player in the formation, maturation, and function of neural circuits. ## Cellular Roles and Expression Landscape The expression pattern of [IGSF21](/details-gene/84966) demonstrates a profound specialization within the nervous system. **Overall**, the gene shows the highest significance in cells crucial for neural development and function. It is a top marker for [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) (CSI: 22.32), suggesting a potential role in the process of myelination. Furthermore, [IGSF21](/details-gene/84966) is highly significant across a diverse set of neuronal subtypes. This includes cells of the retina, such as the [OFF-bipolar cell](/details-cell/CL0000750) (CSI: 21.27) and [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 11.84), as well as numerous cortical neurons. Its prominence in both excitatory neurons, such as [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 17.91) and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 15.61), and inhibitory neurons, including [interneuron](/details-cell/CL0000099) (CSI: 12.22) and [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 12.06), indicates a fundamental role in establishing and maintaining the complex circuitry of the cerebral cortex. Interestingly, significant expression is also noted in [Kupffer cell](/details-cell/CL0000091) (CSI: 11.45), the resident macrophage of the liver, which may indicate a less-characterized function in immune cell adhesion or tissue surveillance outside of the CNS. ## Pathways and Molecular Function Functionally, [IGSF21](/details-gene/84966) is annotated as a cell surface adhesion molecule involved in both [heterophilic cell-cell adhesion](/details-cell/GO0007157) and [homophilic cell adhesion](/details-cell/GO0007156). Its localization on the [external side of plasma membrane](/details-cell/GO0009897) facilitates its role in mediating contact between cells. This general adhesion function is highly specialized within the context of the nervous system. The protein is a known component of synaptic structures, including the [presynaptic membrane](/details-cell/GO0042734), the [postsynaptic density membrane](/details-cell/GO0098839), and specifically at [inhibitory synapse](/details-cell/GO0060077)s. This specific localization underlies its involvement in critical biological processes such as [synapse maturation](/details-cell/GO0060074) and [trans-synaptic signaling, modulating synaptic transmission](/details-cell/GO0099550). These functions are consistent with its high expression across diverse neuronal populations that form the brain's complex signaling network. ## Research Directions The specific expression pattern and functional annotation of [IGSF21](/details-gene/84966) prompt several testable hypotheses regarding its role in neural development and pathology. 1. **Hypothesis 1: Role in Myelination.** The gene's top ranking in [differentiation-committed oligodendrocyte precursors](/details-cell/CL4023059) suggests it is critical for myelination. It is hypothesized that [IGSF21](/details-gene/84966) mediates the initial adhesive interactions between oligodendrocyte processes and neuronal axons, a prerequisite for myelin sheath wrapping. 2. **Hypothesis 2: Regulation of Synaptic Balance.** Given its expression in both glutamatergic and GABAergic neurons and its role in [synapse maturation](/details-cell/GO0060074), [IGSF21](/details-gene/84966) may be a key factor in establishing the excitatory/inhibitory balance in the cerebral cortex. Dysregulation or mutation of [IGSF21](/details-gene/84966) could therefore contribute to neurodevelopmental disorders such as autism or epilepsy, which have been linked to synaptic imbalances. **Proposed Experimental Approach:** To test the role of [IGSF21](/details-gene/84966) in myelination (Hypothesis 1), a CRISPR-Cas9 knockout could be generated in induced pluripotent stem cells (iPSCs), which would then be differentiated into oligodendrocyte precursor cells (OPCs). These knockout and wild-type control OPCs could be co-cultured with primary neurons (e.g., dorsal root ganglion neurons). The efficiency of myelination could be quantitatively assessed by high-content imaging, measuring the length and number of myelin basic protein (MBP)-positive segments formed by the OPCs around the axons. A significant reduction in myelination by the knockout OPCs would confirm the hypothesis. **Therapeutic Potential:** As a cell surface protein, [IGSF21](/details-gene/84966) is an accessible drug target. Its potential role in myelination makes it an attractive candidate for therapies aimed at promoting remyelination in diseases like multiple sclerosis. An agonistic antibody or a small molecule that enhances [IGSF21](/details-gene/84966) adhesion function could potentially be developed to encourage myelin repair. However, given its widespread role in establishing synaptic connections, targeting this gene would require high specificity to avoid unintended neurological side effects, necessitating a much deeper understanding of its precise function in different neural circuits and developmental stages.

Genular Protein ID: 1629509189

Symbol: IGS21_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96ID5 Q8NBR8

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 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16303743

Title: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

PubMed ID: 16303743

DOI: 10.1093/dnares/12.2.117

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 467
  • Mass: 51835
  • Checksum: F62DD2C086A3EDAC
  • Sequence:
    • MRTAPSLRRC VCLLLAAILD LARGYLTVNI EPLPPVVAGD AVTLKCNFKT DGRMREIVWY 
RVTDGGTIKQ KIFTFDAMFS TNYSHMENYR KREDLVYQST VRLPEVRISD NGPYECHVGI 
YDRATREKVV LASGNIFLNV MAPPTSIEVV AADTPAPFSR YQAQNFTLVC IVSGGKPAPM 
VYFKRDGEPI DAVPLSEPPA ASSGPLQDSR PFRSLLHRDL DDTKMQKSLS LLDAENRGGR 
PYTERPSRGL TPDPNILLQP TTENIPETVV SREFPRWVHS AEPTYFLRHS RTPSSDGTVE 
VRALLTWTLN PQIDNEALFS CEVKHPALSM PMQAEVTLVA PKGPKIVMTP SRARVGDTVR 
ILVHGFQNEV FPEPMFTWTR VGSRLLDGSA EFDGKELVLE RVPAELNGSM YRCTAQNPLG 
STDTHTRLIV FENPNIPRGT EDSNGSIGPT GARLTLVLAL TVILELT