Details for: NHSL2

Gene ID: 340527

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: NHSL2

Ensembl ID: ENSG00000204131

Description: NHS like 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • choroid plexus epithelial cell CL0000706
    CSI 32.66
    rCSI 53.48%
    PRS 86.74
  • alveolar type 1 fibroblast cell CL4028004
    CSI 9.87
    rCSI 10.81%
    PRS 94.12
  • elicited macrophage CL0000861
    CSI 6.74
    rCSI 6.19%
    PRS 96.1
  • sst GABAergic cortical interneuron CL4023017
    CSI 5.77
    rCSI 7.44%
    PRS 82.84
  • cerebellar granule cell CL0001031
    CSI 5.11
    rCSI 7.51%
    PRS 88.47
  • blood vessel endothelial cell CL0000071
    CSI 4.94
    rCSI 10.25%
    PRS 91.18
  • fibroblast of lung CL0002553
    CSI 4.64
    rCSI 4.32%
    PRS 93.79
  • chondrocyte CL0000138
    CSI 4.03
    rCSI 6.41%
    PRS 88.78
  • endocardial cell CL0002350
    CSI 4
    rCSI 19.15%
    PRS 89.73
  • hepatic stellate cell CL0000632
    CSI 4
    rCSI 14.98%
    PRS 89.2
  • cytotoxic T cell CL0000910
    CSI 3.5
    rCSI 20.04%
    PRS 90.99
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.46
    rCSI 4.3%
    PRS 79.63
  • mesothelial cell CL0000077
    CSI 3.45
    rCSI 13.47%
    PRS 78.54
  • renal interstitial pericyte CL1001318
    CSI 3.33
    rCSI 9.19%
    PRS 90.68
  • interneuron CL0000099
    CSI 3.33
    rCSI 6.68%
    PRS 87.5
  • adventitial cell CL0002503
    CSI 3.29
    rCSI 7.87%
    PRS 94.5
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.29
    rCSI 2.55%
    PRS 94.39
  • alveolar adventitial fibroblast CL4028006
    CSI 3.25
    rCSI 5.13%
    PRS 93.47
  • respiratory basal cell CL0002633
    CSI 3.1
    rCSI 3.21%
    PRS 93.78
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.01
    rCSI 2.32%
    PRS 95.21
  • hematopoietic stem cell CL0000037
    CSI 2.91
    rCSI 1.94%
    PRS 93.72
  • vascular leptomeningeal cell CL4023051
    CSI 2.76
    rCSI 4.83%
    PRS 89.84
  • bronchus fibroblast of lung CL2000093
    CSI 2.68
    rCSI 2.18%
    PRS 91.88
  • cerebral cortex endothelial cell CL1001602
    CSI 2.23
    rCSI 3.86%
    PRS 88.13
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.21
    rCSI 6.8%
    PRS 93.75
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.21
    rCSI 2.63%
    PRS 81.83
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.14
    rCSI 3.41%
    PRS 94.36
  • ependymal cell CL0000065
    CSI 2.05
    rCSI 4.15%
    PRS 77.04
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.03
    rCSI 3.59%
    PRS 81.06
  • promonocyte CL0000559
    CSI 1.99
    rCSI 3.41%
    PRS 93.88
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.98
    rCSI 7.49%
    PRS 82
  • direct pathway medium spiny neuron CL4023026
    CSI 1.97
    rCSI 47.1%
    PRS 79.57
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.95
    rCSI 47.1%
    PRS 79.68
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.92
    rCSI 3.39%
    PRS 94.89
  • cardiac endothelial cell CL0010008
    CSI 1.89
    rCSI 7.61%
    PRS 93.24
  • parietal epithelial cell CL1000452
    CSI 1.83
    rCSI 4.89%
    PRS 88.45
  • microglial cell CL0000129
    CSI 1.78
    rCSI 7.16%
    PRS 91.33
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.69
    rCSI 2.71%
    PRS 82.79
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.65
    rCSI 1.99%
    PRS 96.18
  • basal cell of epidermis CL0002187
    CSI 1.6
    rCSI 2.83%
    PRS 65.85
  • cerebellar neuron CL1001611
    CSI 1.59
    rCSI 13.95%
    PRS 81.69
  • mononuclear phagocyte CL0000113
    CSI 1.58
    rCSI 3.49%
    PRS 94.72
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.52
    rCSI 5.93%
    PRS 98.57
  • innate lymphoid cell CL0001065
    CSI 1.41
    rCSI 2.91%
    PRS 86.84
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.36
    rCSI 3.45%
    PRS 87.82
  • blood vessel smooth muscle cell CL0019018
    CSI 1.3
    rCSI 10.54%
    PRS 90.86
  • mesenchymal cell CL0008019
    CSI 1.29
    rCSI 3.28%
    PRS 88.3
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.28
    rCSI 3.1%
    PRS 79.64
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.25
    rCSI 2.09%
    PRS 81.84
  • suprabasal keratinocyte CL4033013
    CSI 1.22
    rCSI 2%
    PRS 65.85
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.11
    rCSI 1.34%
    PRS 74.56
  • medium spiny neuron CL1001474
    CSI 1.08
    rCSI 9.3%
    PRS 85.73
  • helper T cell CL0000912
    CSI 1.05
    rCSI 1.48%
    PRS 88.22
  • cardiac blood vessel endothelial cell CL0010006
    CSI 0.86
    rCSI 6.08%
    PRS 87.27
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.78
    rCSI 2.42%
    PRS 82.94
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.52
    rCSI 3.14%
    PRS 96.65

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.

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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 [NHSL2](/details-gene/340527) (NHS like 2) is a protein-coding gene located on the X chromosome ([Link](https://doi.org/10.1038/nature03440)). Functionally, it is annotated with roles in [protein binding](/details-go/GO:0005515) and [cell differentiation](/details-go/GO:0030154). Expression data reveals a remarkably specific and high-significance profile in [choroid plexus epithelial cells](/details-cell/CL0000706), suggesting it is a key marker and potentially a crucial functional component of this specialized tissue. While its expression is most prominent in the choroid plexus, [NHSL2](/details-gene/340527) also shows moderate significance across a diverse range of cell types, including fibroblasts, neurons, and immune cells, indicating a potentially pleiotropic role in multiple biological systems. Its clinical association is noted in OMIM ([301093](https://omim.org/entry/301093)). ## Cellular Roles and Expression Landscape The expression profile of [NHSL2](/details-gene/340527) is dominated by its exceptionally high significance in [choroid plexus epithelial cells](/details-cell/CL0000706) (CSI: 32.66), a score that is more than three times higher than any other cell type in the **Overall** context. This positions [NHSL2](/details-gene/340527) as a defining molecular marker for this cell type, which is critical for producing cerebrospinal fluid and forming the blood-cerebrospinal fluid barrier. Beyond this specialized role, [NHSL2](/details-gene/340527) demonstrates a broad, albeit lower-level, expression pattern, suggesting multifaceted functions. It shows notable significance in several distinct cellular lineages: * **Fibroblastic and Mesenchymal Cells:** The gene is significantly expressed in [alveolar type 1 fibroblast cells](/details-cell/CL4028004), [fibroblasts of lung](/details-cell/CL0002553), [chondrocytes](/details-cell/CL0000138), and [hepatic stellate cells](/details-cell/CL0000632), implying a potential role in connective tissue maintenance, extracellular matrix organization, or wound healing. * **Immune Cells:** Significant expression in [elicited macrophages](/details-cell/CL0000861) and [cytotoxic T cells](/details-cell/CL0000910) suggests a possible involvement in immune cell function or activation. * **Neural Cells:** Its presence in various neuronal subtypes, including [sst GABAergic cortical interneurons](/details-cell/CL4023017), [cerebellar granule cells](/details-cell/CL0001031), and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018), points to a potential role in the central nervous system, separate from its primary function in the choroid plexus. * **Endothelial and Epithelial Cells:** The gene is also active in [blood vessel endothelial cells](/details-cell/CL0000071), [endocardial cells](/details-cell/CL0002350), and [mesothelial cells](/details-cell/CL0000077), indicating a role in the lining of vascular and body cavities. This widespread, heterogeneous expression pattern suggests that [NHSL2](/details-gene/340527) may act as a versatile adapter or scaffolding protein involved in processes common to many cell types, while serving a highly specialized and indispensable function within the choroid plexus. ## Pathways and Molecular Function The known functional annotations for [NHSL2](/details-gene/340527) align well with its observed expression profile. Its role in [cell differentiation](/details-go/GO:0030154) is consistent with its expression across multiple, distinct cell lineages, from neurons to fibroblasts to immune cells. This suggests [NHSL2](/details-gene/340527) may be involved in the establishment or maintenance of these varied cellular identities. The gene's fundamental molecular function is described as [protein binding](/details-go/GO:0005515). This function is likely central to its roles in all contexts. In [choroid plexus epithelial cells](/details-cell/CL0000706), [NHSL2](/details-gene/340527) may mediate protein-protein interactions essential for the tight junction integrity of the blood-CSF barrier, ion transport machinery, or cerebrospinal fluid secretion. In other cell types like fibroblasts and macrophages, it could be involved in organizing the cytoskeleton or participating in signaling complexes that regulate cell adhesion, migration, or response to stimuli. The identification of this gene within a large-scale cDNA collection ([Link](https://doi.org/10.1101/gr.2596504)) and a phosphoproteomics screen ([Link](https://doi.org/10.1073/pnas.0805139105)) further suggests it is a component of dynamic cellular signaling networks. ## Research Directions The unique expression pattern of [NHSL2](/details-gene/340527) provides a strong basis for further investigation into its specific biological roles, particularly concerning the central nervous system and tissue homeostasis. **Proposed Hypotheses:** 1. **[NHSL2](/details-gene/340527) is a critical regulator of blood-cerebrospinal fluid barrier integrity.** Given its exceptional expression in [choroid plexus epithelial cells](/details-cell/CL0000706) and its annotation in [protein binding](/details-go/GO:0005515), it may function as a key scaffolding protein that organizes the tight junction complexes or ion channels necessary for barrier function and CSF production. 2. **[NHSL2](/details-gene/340527) functions as a modulator of cellular response to tissue injury.** Its significant expression in fibroblasts, macrophages, and endothelial cells—all key players in inflammation and wound healing—suggests it could play a role in coordinating tissue remodeling, fibrosis, or angiogenesis following damage. **Experimental Approach:** To test the first hypothesis, the role of [NHSL2](/details-gene/340527) in the choroid plexus could be investigated using an *in vitro* organoid model. CRISPR-Cas9-mediated knockout of [NHSL2](/details-gene/340527) in human pluripotent stem cells could be followed by differentiation into choroid plexus organoids. The resulting organoids could be assessed for defects in morphology, proliferation, and, most importantly, barrier function using transepithelial electrical resistance (TEER) measurements and permeability assays with fluorescent tracers. Furthermore, co-immunoprecipitation followed by mass spectrometry (IP-MS) in a choroid plexus cell line could identify its binding partners, revealing the specific cellular machinery it interacts with to maintain barrier integrity. **Therapeutic Potential:** The highly specific expression of [NHSL2](/details-gene/340527) in the choroid plexus makes it an attractive candidate for multiple clinical applications. If its dysregulation is linked to neurological disorders involving blood-CSF barrier breakdown (e.g., in meningitis, multiple sclerosis, or Alzheimer's disease), it could serve as a highly specific biomarker in cerebrospinal fluid. As a therapeutic target, its specificity suggests that modulating its function would have minimal off-target effects in other tissues. For instance, if [NHSL2](/details-gene/340527) loss-of-function contributes to hydrocephalus, gene therapies aimed at restoring its expression could be a viable strategy. Conversely, it could be exploited as a target for drug delivery systems designed to transport therapeutics across the blood-CSF barrier into the central nervous system.

Genular Protein ID: 4031826783

Symbol: NHSL2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q5HYW2 A0A0J9YY34 B2RN94

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 1 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 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 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

Sequence Information:

  • Length: 1225
  • Mass: 133286
  • Checksum: 84681065AD4F7D5E
  • Sequence:
    • MPFYRRTVVP QRLCPRNPPQ QLAELRDVSH LAALSLLRQL ADLCGHSLAL LEDLEGHLLA 
LGRRTDSLYR RTVRLRRRLP CRLLGPEEDE EELAAANSGR ENATATAHSR SSWRQPVNVF 
LSSGRPPSVE ELLREAQLNL QSLLQEEYEE QYSEARLVGQ TFRSSDEATK PTPNPRPQSA 
RRLEFILMPT KRQLSEDETT TQGVRAPEAS LSLSTTADKQ TAWNSLFPLP ILEEKRWPQL 
CSTQSDIVPI NISGQQFDKH ASLRHSLFNT ETAVNPKSTL RRRRTIIGFS NFSQRDQGHS 
NSPAGSVAHS TTSDIRPSHS VPEGVHGRVA VGQDARFPSL TSPVLRTPSS EPDEPHQARS 
GPNPPGMESM GMVYSVPSSC NGPTESTFST SWKGDAFTYM TPSATSQSNQ VNENGKNPSC 
GNSWVSLNKV PPLVPKEAAT LLVARDNPAG CSGSAGYPER LIQQRHMPER PSKIGLLTSG 
TSRLETGPGG ASRFRERSLS VPTDSGTTDV DYDEEQKANE ACALPFASTS SEGSNSADNI 
ASLSAQQEAQ HRRQRSKSIS LRKAKKKPSP PTRSVSLVKD EPGLLPEGGS ALPKDQRPKS 
LCLSLEHQGH HSSHPDAQGH PAIPNHKDPE STQFSHHWYL TDWKSGDTYQ SLSSSSTATG 
TTVIECTQVQ GSSESLASPS TSRATTPSQL SIEVEAREIS SPGRPPGLMS PSSGYSSQSE 
TPTPTVSMSL TLGHLPPPSS SVRVRPVVPE RKSSLPPTSP MEKFPKSRLS FDLPLTSSPN 
LDLSGMSISI RSKTKVSRHH SETNFGVKLA QKTNPNQPIM PMVTQSDLRS VRLRSVSKSE 
PEDDIESPEY AEEPRAEEVF TLPERKTKPP VAEKPPVARR PPSLVHKPPS VPEEYALTSP 
TLAMPPRSSI QHARPLPQDS YTVVRKPKPS SFPDGRSPGE STAPSSLVFT PFASSSDAFF 
SGTQQPPQGS VEDEGPKVRV LPERISLQSQ EEAEKKKGKI PPPVPKKPSV LYLPLTSPTA 
QMEAYVAEPR LPLSPIITLE EDTKCPATGD DLQSLGQRVT STPQADSERE ASPLGSSVEP 
GTEEKSLISD KTAEWIAEDD DDVFVASRTT EDLFTVIHRS KRKLLGWKEP GEAFVGGRTS 
SHSPIKNTAE SPISESTATA GSGSSANLDA GRNDDFKALL QKKGSKATPR SRPSAAELLK 
TTNPLARRII AQFSKDYETT DNPST