Details for: LRFN2

Gene ID: 57497

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: LRFN2

Ensembl ID: ENSG00000156564

Description: leucine rich repeat and fibronectin type III domain containing 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 49.51
    rCSI 59.14%
    PRS 98.23
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 25.96
    rCSI 45.85%
    PRS 98.25
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 21.57
    rCSI 52.42%
    PRS 97.6
  • L6b glutamatergic cortical neuron CL4023038
    CSI 15.9
    rCSI 49.68%
    PRS 98.24
  • sncg GABAergic cortical interneuron CL4023015
    CSI 15.15
    rCSI 24.36%
    PRS 98.15
  • rod bipolar cell CL0000751
    CSI 13.22
    rCSI 23.76%
    PRS 98.83
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 12.83
    rCSI 15.97%
    PRS 97.99
  • sst GABAergic cortical interneuron CL4023017
    CSI 12.34
    rCSI 15.9%
    PRS 98.56
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 12.09
    rCSI 26.22%
    PRS 97.18
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 11.75
    rCSI 42.28%
    PRS 97.9
  • retinal rod cell CL0000604
    CSI 10.37
    rCSI 18.28%
    PRS 98.56
  • neuron CL0000540
    CSI 10.36
    rCSI 27.59%
    PRS 96.95
  • inhibitory interneuron CL0000498
    CSI 9.42
    rCSI 21.76%
    PRS 98.35
  • retinal cone cell CL0000573
    CSI 9.31
    rCSI 14.99%
    PRS 98.12
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.41
    rCSI 49.5%
    PRS 97.99
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 8.35
    rCSI 27.43%
    PRS 97.29
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 8.09
    rCSI 19.35%
    PRS 97.61
  • neural progenitor cell CL0011020
    CSI 7.38
    rCSI 32.46%
    PRS 96.47
  • retinal bipolar neuron CL0000748
    CSI 7.1
    rCSI 13.29%
    PRS 98.36
  • astrocyte of the cerebral cortex CL0002605
    CSI 6.96
    rCSI 15.61%
    PRS 98.4
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 5.63
    rCSI 9.45%
    PRS 98.41
  • glutamatergic neuron CL0000679
    CSI 5.29
    rCSI 10.87%
    PRS 96.76
  • parietal epithelial cell CL1000452
    CSI 5.14
    rCSI 13.73%
    PRS 99.18
  • retinal ganglion cell CL0000740
    CSI 5.03
    rCSI 11.12%
    PRS 98.25
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.5
    rCSI 17.01%
    PRS 97.89
  • serotonergic neuron CL0000850
    CSI 4.43
    rCSI 19.77%
    PRS 96.52
  • dopaminergic neuron CL0000700
    CSI 4.06
    rCSI 22.94%
    PRS 97.78
  • GABAergic neuron CL0000617
    CSI 4.03
    rCSI 13.51%
    PRS 96.56
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.02
    rCSI 5.49%
    PRS 98.62
  • central nervous system neuron CL2000029
    CSI 2.87
    rCSI 21.09%
    PRS 98.53
  • ON parasol ganglion cell CL4033052
    CSI 2.13
    rCSI 30.25%
    PRS 98.12
  • invaginating midget bipolar cell CL4033034
    CSI 1.53
    rCSI 9.05%
    PRS 97.55
  • ON midget ganglion cell CL4033046
    CSI 0.61
    rCSI 12.37%
    PRS 98.03

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 [LRFN2](/details-gene/57497) (leucine rich repeat and fibronectin type III domain containing 2) is a protein-coding gene located on chromosome 6. It encodes a member of the SALM (Synaptic adhesion-like molecules) family of proteins, which are characterized by leucine-rich repeat and fibronectin type-III domains. Functionally, [LRFN2](/details-gene/57497) is integral to the organization and modulation of synapses within the central nervous system. Expression data reveals its highly specific and significant role in various neuronal subtypes, including a prominent association with diverse classes of cortical interneurons and glutamatergic neurons, suggesting it is a key regulator of synaptic architecture and transmission. ## Cellular Roles and Expression Landscape The expression profile of [LRFN2](/details-gene/57497) firmly establishes it as a neuron-specific gene with a critical role in the cerebral cortex and retina. **Overall**, the gene shows the highest significance in inhibitory interneuron populations, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 49.51) and [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 25.96), as well as other major interneuron classes such as those expressing Pvalb and Sst. This suggests a fundamental role for [LRFN2](/details-gene/57497) in establishing or maintaining inhibitory circuits. In parallel, [LRFN2](/details-gene/57497) is also a significant marker for multiple excitatory glutamatergic neuron subtypes, such as [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 21.57) and [L6b glutamatergic cortical neuron](/details-cell/CL4023038) (CSI: 15.90). Its co-expression in both major excitatory and inhibitory neuronal classes points towards a role in orchestrating the assembly and balance of cortical microcircuits. Beyond the cortex, its notable expression in retinal cells, including [rod bipolar cell](/details-cell/CL0000751) and [retinal rod cell](/details-cell/CL0000604), indicates its function extends to synaptic organization in other specialized neural tissues. The highly restricted expression pattern to these specialized [neurons](/details-cell/CL0000540) underscores its specific function within the nervous system. ## Pathways and Molecular Function The molecular functions of [LRFN2](/details-gene/57497) are centered on synaptic cell adhesion and organization. As a [cell surface](/details-go/GO:0009986) and [plasma membrane](/details-go/GO:0005886) protein, it is localized to critical synaptic compartments, including the [postsynaptic density membrane](/details-go/GO:0098839) and the [presynapse](/details-go/GO:0098793). This localization is consistent with its involvement in Reactome pathways such as [Synaptic adhesion-like molecules](/details-reactome/R-HSA-8849932) and [Protein-protein interactions at synapses](/details-reactome/R-HSA-6794362). Functionally, these roles converge on the [modulation of chemical synaptic transmission](/details-go/GO:0050804) and the [regulation of postsynapse organization](/details-go/GO:0099175). Research has shown that SALM family members, including [LRFN2](/details-gene/57497), regulate the differentiation of excitatory synapses, a role supported by its high expression in glutamatergic neurons [Link](https://doi.org/10.1016/j.neuron.2006.04.005). Its broader involvement in the [Neuronal system](/details-reactome/R-HSA-112316) highlights its fundamental importance in building and maintaining the brain's complex wiring. ## Research Directions The specific and high-level expression of [LRFN2](/details-gene/57497) across distinct but interacting neuronal populations suggests several avenues for future research into neural circuit formation and function. ### Testable Hypotheses 1. **Hypothesis on Inhibitory Circuit Specificity:** Given its high significance in multiple, distinct interneuron subtypes ([VIP](/details-cell/CL4023016), [sst](/details-cell/CL4023017), [pvalb](/details-cell/CL4023018)), we hypothesize that [LRFN2](/details-gene/57497) acts as a molecular code that dictates the target specificity and synaptic properties of different inhibitory circuits. Its differential expression levels may fine-tune the connectivity of these interneurons with their postsynaptic partners. 2. **Hypothesis on Excitation-Inhibition Balance:** Based on its expression in both excitatory glutamatergic and inhibitory GABAergic [neurons](/details-cell/CL0000540), we propose that [LRFN2](/details-gene/57497) mediates the precise apposition of excitatory and inhibitory synapses onto target [neurons](/details-cell/CL0000540), thereby playing a crucial role in establishing and maintaining the excitation-inhibition balance that is critical for proper cortical function. ### Proposed Experiment To test the first hypothesis regarding its role in inhibitory circuit specificity, a conditional knockout (cKO) approach in mice would be highly informative. By crossing a `Lrfn2-floxed` mouse line with a subtype-specific Cre-driver line (e.g., `Pvalb-Cre`), one could selectively delete [LRFN2](/details-gene/57497) from parvalbumin-positive interneurons. The consequences could be assessed using a combination of techniques: * **Electrophysiology:** Perform whole-cell patch-clamp recordings from pyramidal [neurons](/details-cell/CL0000540) to measure changes in the frequency and amplitude of spontaneous and evoked inhibitory postsynaptic currents (IPSCs) originating from PV-interneurons. * **Anatomy:** Use immunohistochemistry to quantify the number and localization of synaptic puncta (e.g., staining for VGAT and Gephyrin) from PV-interneuron axons onto their target cells in cKO versus control animals. * **Behavior:** Assess for behavioral deficits associated with PV-interneuron dysfunction, such as altered sensory processing or susceptibility to seizures. ### Therapeutic Potential As a cell-surface protein highly specific to the central nervous system, [LRFN2](/details-gene/57497) presents a theoretically attractive target. However, its fundamental role in synaptic organization suggests that systemic modulation could lead to profound and undesirable neurological side effects. Its therapeutic potential may lie in addressing neuropsychiatric or neurological disorders characterized by synaptic dysregulation, such as epilepsy, autism spectrum disorders, or schizophrenia. Rather than broad inhibition or activation, a more nuanced strategy involving allosteric modulators that fine-tune its specific protein-protein interactions could be explored. The primary challenge remains the blood-brain barrier, suggesting that any therapeutic agent would require sophisticated delivery mechanisms. Therefore, while [LRFN2](/details-gene/57497) is a compelling biological molecule, its direct utility as a therapeutic target is currently limited by the high risk of disrupting essential neural functions.

Genular Protein ID: 504383495

Symbol: LRFN2_HUMAN

Name: Leucine-rich repeat and fibronectin type-III domain-containing protein 2

UniProtKB Accession Codes:

Q9ULH4 A5PKU3 Q5SYP9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 7 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 13 KEGG 1 MANE-Select 1 MIM 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 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 4 SIGNOR 1 SMART 4 SMR 1 STRING 1 SUPFAM 3 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 16630835

Title: SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses.

PubMed ID: 16630835

DOI: 10.1016/j.neuron.2006.04.005

Sequence Information:

  • Length: 789
  • Mass: 84731
  • Checksum: 3D1D298909267F38
  • Sequence:
    • METLLGGLLA FGMAFAVVDA CPKYCVCQNL SESLGTLCPS KGLLFVPPDI DRRTVELRLG 
GNFIIHISRQ DFANMTGLVD LTLSRNTISH IQPFSFLDLE SLRSLHLDSN RLPSLGEDTL 
RGLVNLQHLI VNNNQLGGIA DEAFEDFLLT LEDLDLSYNN LHGLPWDSVR RMVNLHQLSL 
DHNLLDHIAE GTFADLQKLA RLDLTSNRLQ KLPPDPIFAR SQASALTATP FAPPLSFSFG 
GNPLHCNCEL LWLRRLERDD DLETCGSPGG LKGRYFWHVR EEEFVCEPPL ITQHTHKLLV 
LEGQAATLKC KAIGDPSPLI HWVAPDDRLV GNSSRTAVYD NGTLDIFITT SQDSGAFTCI 
AANAAGEATA MVEVSIVQLP HLSNSTSRTA PPKSRLSDIT GSSKTSRGGG GSGGGEPPKS 
PPERAVLVSE VTTTSALVKW SVSKSAPRVK MYQLQYNCSD DEVLIYRMIP ASNKAFVVNN 
LVSGTGYDLC VLAMWDDTAT TLTATNIVGC AQFFTKADYP QCQSMHSQIL GGTMILVIGG 
IIVATLLVFI VILMVRYKVC NHEAPSKMAA AVSNVYSQTN GAQPPPPSSA PAGAPPQGPP 
KVVVRNELLD FTASLARASD SSSSSSLGSG EAAGLGRAPW RIPPSAPRPK PSLDRLMGAF 
ASLDLKSQRK EELLDSRTPA GRGAGTSARG HHSDREPLLG PPAARARSLL PLPLEGKAKR 
SHSFDMGDFA AAAAGGVVPG GYSPPRKVSN IWTKRSLSVN GMLLPFEESD LVGARGTFGS 
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