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    NSMAF neutral sphingomyelinase activation associated factor [ Homo sapiens (human) ]

    Gene ID: 8439, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NSMAFprovided by HGNC
    Official Full Name
    neutral sphingomyelinase activation associated factorprovided by HGNC
    Primary source
    HGNC:HGNC:8017
    See related
    Ensembl:ENSG00000035681 MIM:603043; AllianceGenome:HGNC:8017
    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
    FAN; GRAMD5
    Summary
    This gene encodes a WD-repeat protein that binds the cytoplasmic sphingomyelinase activation domain of the 55kD tumor necrosis factor receptor. This protein is required for TNF-mediated activation of neutral sphingomyelinase and may play a role in regulating TNF-induced cellular responses such as inflammation. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
    Expression
    Ubiquitous expression in lymph node (RPKM 12.0), appendix (RPKM 10.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NSMAF in Genome Data Viewer
    Location:
    8q12.1
    Exon count:
    39
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (58583504..58659853, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (59004662..59081032, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (59496063..59572412, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene peptidylprolyl isomerase A pseudogene 85 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:59465479-59466196 Neighboring gene syndecan binding protein Neighboring gene MED14-independent group 3 enhancer GRCh37_chr8:59507186-59508385 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27412 Neighboring gene ribosomal protein S26 pseudogene 7 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:59558003-59558563 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:59563765-59564489 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:59570852-59571415 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:59571416-59571978 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19219 Neighboring gene small nucleolar RNA U13 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:59581817-59582504 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr8:59584567-59585254 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr8:59612775-59613346 Neighboring gene uncharacterized LOC105375858

    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. New variant identified in major susceptibility locus to tuberculosis on chromosomal region 8q12-q13 in Moroccan population: a case control study. Qrafli M, et al. BMC Infect Dis, 2017 Nov 7. PMID 29115933, Free PMC Article
    2. Assignment of the human FAN protein gene (NSMAF) to human chromosome region 8q12-->q13 by in situ hybridization. Zhang Y, et al. Cytogenet Cell Genet, 1999. PMID 10640829
    3. Functional characterization of the postulated intramolecular sphingolipid activator protein domain of human acid sphingomyelinase. Kölzer M, et al. Biol Chem, 2004 Dec. PMID 15653433
    4. Caspase-2 associates with FAN through direct interaction and overlapping functionality. Forsberg J, et al. Biochem Biophys Res Commun, 2018 May 23. PMID 29621545
    5. CD40 signals apoptosis through FAN-regulated activation of the sphingomyelin-ceramide pathway. Ségui B, et al. J Biol Chem, 1999 Dec 24. PMID 10601289

    See all (27) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. these data identify a novel caspase-2-interacting factor, FAN, and expand the role for the enzyme in seemingly non-apoptotic cellular mechanisms.
      Title: Caspase-2 associates with FAN through direct interaction and overlapping functionality.
    2. The rs1050504 C > T genotype was observed to be significantly associated with an increased risk for developing pulmonary tuberculosis.
      Title: New variant identified in major susceptibility locus to tuberculosis on chromosomal region 8q12-q13 in Moroccan population: a case control study.
    3. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
    5. Regulation of NSMAF by TNF-alpha involves PRKCD in lung epithelial cells.
      Title: Regulation of neutral sphingomyelinase-2 (nSMase2) by tumor necrosis factor-alpha involves protein kinase C-delta in lung epithelial cells.
    6. sphingolipid activator proteins like domain may stabilize the fold of acid sphingomyelinase
      Title: Functional characterization of the postulated intramolecular sphingolipid activator protein domain of human acid sphingomyelinase.
    7. The interaction of FAN with receptor for activated C-kinase 1 (RACK1) appears to be dependent on the folding of the WD repeats into a secondary structure, because no linear binding motifs are identified in the WD-repeat region of FAN.
      Title: Interaction with factor associated with neutral sphingomyelinase activation, a WD motif-containing protein, identifies receptor for activated C-kinase 1 as a novel component of the signaling pathways of the p55 TNF receptor.
    Submit: New GeneRIF Correction

    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

    EBI GWAS Catalog

    Description
    Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sphingomyelin phosphodiesterase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in ceramide metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of amide metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of membrane lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in tumor necrosis factor-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein FAN
    Names
    factor associated with N-SMase activation
    factor associated with neutral sphingomyelinase activation
    neutral sphingomyelinase (N-SMase) activation associated factor

    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.

    mRNA and Protein(s)

    1. NM_001144772.1 → NP_001138244.1  protein FAN isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR and coding region. Isoform 2 has a longer N-terminus, compared to isoform 1.
      Source sequence(s)
      AC068522, AK294009, BC041124
      Consensus CDS
      CCDS47864.1
      UniProtKB/TrEMBL
      B2RA06
      Related
      ENSP00000411012.2, ENST00000427130.7
      Conserved Domains (5) summary
      COG2319
      Location:645 → 947
      WD40; WD40 repeat [General function prediction only]
      cd00200
      Location:653 → 945
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      pfam02138
      Location:335 → 606
      Beach; Beige/BEACH domain
      sd00039
      Location:664 → 701
      7WD40; WD40 repeat [structural motif]
      cl17171
      Location:223 → 316
      PH-like; Pleckstrin homology-like domain

    2. NM_001412988.1 → NP_001399917.1  protein FAN isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      A8K9G4, B2RA06

    3. NM_001412989.1 → NP_001399918.1  protein FAN isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      A8K9G4, B2RA06

    4. NM_001412990.1 → NP_001399919.1  protein FAN isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    5. NM_001412991.1 → NP_001399920.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    6. NM_001412992.1 → NP_001399921.1  protein FAN isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    7. NM_001412993.1 → NP_001399922.1  protein FAN isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    8. NM_001412994.1 → NP_001399923.1  protein FAN isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    9. NM_001412995.1 → NP_001399924.1  protein FAN isoform 10

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    10. NM_001412996.1 → NP_001399925.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    11. NM_001412997.1 → NP_001399926.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    12. NM_001412998.1 → NP_001399927.1  protein FAN isoform 11

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    13. NM_001412999.1 → NP_001399928.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    14. NM_001413000.1 → NP_001399929.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    15. NM_001413001.1 → NP_001399930.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    16. NM_001413002.1 → NP_001399931.1  protein FAN isoform 12

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      A8K9G4, B2RA06

    17. NM_001413003.1 → NP_001399932.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    18. NM_001413004.1 → NP_001399933.1  protein FAN isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    19. NM_001413005.1 → NP_001399934.1  protein FAN isoform 16

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    20. NM_001413006.1 → NP_001399935.1  protein FAN isoform 13

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      UniProtKB/TrEMBL
      B2RA06

    21. NM_001413007.1 → NP_001399936.1  protein FAN isoform 14

      Status: REVIEWED

      Source sequence(s)
      AC068522

    22. NM_001413008.1 → NP_001399937.1  protein FAN isoform 14

      Status: REVIEWED

      Source sequence(s)
      AC068522

    23. NM_001413009.1 → NP_001399938.1  protein FAN isoform 15

      Status: REVIEWED

      Source sequence(s)
      AC068522

    24. NM_003580.4 → NP_003571.2  protein FAN isoform 1

      See identical proteins and their annotated locations for NP_003571.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the shorter isoform (1).
      Source sequence(s)
      AC068522, AC092700, BC041124, DR005814
      Consensus CDS
      CCDS6173.1
      UniProtKB/Swiss-Prot
      B4DFB0, E9PCH0, Q8IW26, Q92636
      UniProtKB/TrEMBL
      B2RA06
      Related
      ENSP00000038176.3, ENST00000038176.8
      Conserved Domains (4) summary
      cd00200
      Location:622 → 914
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      sd00039
      Location:633 → 670
      7WD40; WD40 repeat [structural motif]
      pfam02138
      Location:304 → 575
      Beach; Beige/BEACH domain
      cl17171
      Location:192 → 285
      PH-like; Pleckstrin homology-like domain

    RNA

    1. NR_182084.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700
      Related
      ENST00000649465.1

    2. NR_182085.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700

    3. NR_182086.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700

    4. NR_182087.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700

    5. NR_182088.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700

    6. NR_182089.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC068522, AC092700

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      58583504..58659853 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047422320.1 → XP_047278276.1  protein FAN isoform X1

      UniProtKB/TrEMBL
      B2RA06

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      59004662..59081032 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054361353.1 → XP_054217328.1  protein FAN isoform X1

      UniProtKB/TrEMBL
      B2RA06
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92636.2 GenPept UniProtKB/Swiss-Prot:Q92636

    Gene LinkOut

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

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