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    MANF mesencephalic astrocyte derived neurotrophic factor [ Homo sapiens (human) ]

    Gene ID: 7873, updated on 5-May-2024

    Summary

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    Official Symbol
    MANFprovided by HGNC
    Official Full Name
    mesencephalic astrocyte derived neurotrophic factorprovided by HGNC
    Primary source
    HGNC:HGNC:15461
    See related
    Ensembl:ENSG00000145050 MIM:601916; AllianceGenome:HGNC:15461
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ARP; DDDS; ARMET
    Summary
    The protein encoded by this gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this protein is important in promoting the survival of dopaminergic neurons. The presence of polymorphisms in the N-terminal arginine-rich region, including a specific mutation that changes an ATG start codon to AGG, have been reported in a variety of solid tumors; however, these polymorphisms were later shown to exist in normal tissues and are thus no longer thought to be tumor-related. [provided by RefSeq, Apr 2014]
    Expression
    Ubiquitous expression in thyroid (RPKM 71.3), appendix (RPKM 44.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MANF in Genome Data Viewer
    Location:
    3p21.2
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (51385291..51389397)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (51415711..51419814)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (51422722..51426828)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene dedicator of cytokinesis 3 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:50828090-50828836 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50855181-50855760 Neighboring gene zinc finger protein 652 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19915 Neighboring gene NANOG hESC enhancer GRCh37_chr3:50928312-50928861 Neighboring gene Sharpr-MPRA regulatory region 894 Neighboring gene ST13, Hsp70 interacting protein pseudogene 14 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14407 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:51263456-51264655 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19916 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:51377300-51378184 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19917 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14408 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19918 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14409 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14410 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14411 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51430225-51430730 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:51430731-51431238 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14412 Neighboring gene RNA binding motif protein 15B Neighboring gene DDB1 and CUL4 associated factor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19919 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14413 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14414 Neighboring gene uncharacterized LOC105377085 Neighboring gene Sharpr-MPRA regulatory region 10823

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Prognostic potential of serum mesencephalic astrocyte-derived neurotrophic factor in acute intracerebral hemorrhage: a prospective observational study. Zhang CL, et al. BMC Neurol, 2023 Jun 2. PMID 37268902, Free PMC Article
    2. A prospective observational study on utility of serum mesencephalic astrocyte-derived neurotrophic factor as a promising prognostic biomarker of severe traumatic brain injury in humans. Wang KW, et al. Clin Chim Acta, 2023 May 1. PMID 37137461
    3. Mesencephalic astrocyte-derived neurotrophic factor (MANF) prevents the neuroinflammation induced dopaminergic neurodegeneration. Zhang JX, et al. Exp Gerontol, 2023 Jan. PMID 36436758
    4. MANF Inhibits α-Synuclein Accumulation through Activation of Autophagic Pathways. Zhang JX, et al. Oxid Med Cell Longev, 2022. PMID 35847585, Free PMC Article
    5. Mesencephalic astrocyte-derived neurotrophic factor attenuates acute lung injury via inhibiting macrophages' activation. Shen QY, et al. Biomed Pharmacother, 2022 Jun. PMID 35405395

    See all (86) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MANF protein expression is upregulated in immune cells in the ischemic human brain and systemic recombinant MANF delivery in rat ischemic stroke model demonstrates anti-inflammatory effects.
      Title: MANF protein expression is upregulated in immune cells in the ischemic human brain and systemic recombinant MANF delivery in rat ischemic stroke model demonstrates anti-inflammatory effects.
    2. Deletion of mesencephalic astrocyte-derived neurotrophic factor delays and damages the development of white pulp in spleen.
      Title: Deletion of mesencephalic astrocyte-derived neurotrophic factor delays and damages the development of white pulp in spleen.
    3. Serum levels of interleukin-33 and mesencephalic astrocyte derived neurotrophic factors in patients with major depressive disorder: a cross-sectional comparative design.
      Title: Serum levels of interleukin-33 and mesencephalic astrocyte derived neurotrophic factors in patients with major depressive disorder: a cross-sectional comparative design.
    4. MANF inhibits Sjogren's syndrome salivary gland epithelial cell apoptosis and antigen expression of Ro52/SSA through endoplasmic reticulum stress/autophagy pathway.
      Title: MANF inhibits Sjögren's syndrome salivary gland epithelial cell apoptosis and antigen expression of Ro52/SSA through endoplasmic reticulum stress/autophagy pathway.
    5. Prognostic potential of serum mesencephalic astrocyte-derived neurotrophic factor in acute intracerebral hemorrhage: a prospective observational study.
      Title: Prognostic potential of serum mesencephalic astrocyte-derived neurotrophic factor in acute intracerebral hemorrhage: a prospective observational study.
    6. A prospective observational study on utility of serum mesencephalic astrocyte-derived neurotrophic factor as a promising prognostic biomarker of severe traumatic brain injury in humans.
      Title: A prospective observational study on utility of serum mesencephalic astrocyte-derived neurotrophic factor as a promising prognostic biomarker of severe traumatic brain injury in humans.
    7. Mesencephalic astrocyte-derived neurotrophic factor (MANF) prevents the neuroinflammation induced dopaminergic neurodegeneration.
      Title: Mesencephalic astrocyte-derived neurotrophic factor (MANF) prevents the neuroinflammation induced dopaminergic neurodegeneration.
    8. MANF Inhibits alpha-Synuclein Accumulation through Activation of Autophagic Pathways.
      Title: MANF Inhibits α-Synuclein Accumulation through Activation of Autophagic Pathways.
    9. Mesencephalic astrocyte-derived neurotrophic factor attenuates acute lung injury via inhibiting macrophages' activation.
      Title: Mesencephalic astrocyte-derived neurotrophic factor attenuates acute lung injury via inhibiting macrophages' activation.
    10. Mesencephalic astrocyte-derived neurotrophic factor reprograms macrophages to ameliorate acetaminophen-induced acute liver injury via p38 MAPK pathway.
      Title: Mesencephalic astrocyte-derived neurotrophic factor reprograms macrophages to ameliorate acetaminophen-induced acute liver injury via p38 MAPK pathway.
    Submit: New GeneRIF Correction See all GeneRIFs (41)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Diabetes, deafness, developmental delay, and short stature syndrome
    MedGen: CN375862 OMIM: 620651 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC142148, MGC142150

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables growth factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sulfatide binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in dopaminergic neuron differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neuron projection development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to unfolded protein IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum lumen IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus HDA PubMed 
    located_in sarcoplasmic reticulum lumen IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    mesencephalic astrocyte-derived neurotrophic factor
    Names
    arginine-rich, mutated in early stage tumors

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012652.3 RefSeqGene

      Range
      5020..9126
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006010.6 → NP_006001.5  mesencephalic astrocyte-derived neurotrophic factor precursor

      Status: REVIEWED

      Source sequence(s)
      BC007282, M83751
      Consensus CDS
      CCDS46836.4
      UniProtKB/Swiss-Prot
      P55145, Q14CX4, Q86U67, Q96IS4
      UniProtKB/TrEMBL
      A8K878
      Related
      ENSP00000432799.3, ENST00000528157.7
      Conserved Domains (1) summary
      pfam10208
      Location:29 → 173
      Armet; Degradation arginine-rich protein for mis-folding

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      51385291..51389397
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      51415711..51419814
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P55145.3 GenPept UniProtKB/Swiss-Prot:P55145

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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