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

Gene ID: 8439, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (58583504..58659853, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (59004662..59081032, complement)
105.20220307 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. Functional characterization of the postulated intramolecular sphingolipid activator protein domain of human acid sphingomyelinase. Kölzer M, et al. Biol Chem, 2004 Dec. PMID 15653433
  3. 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
  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. Regulation of neutral sphingomyelinase-2 (nSMase2) by tumor necrosis factor-alpha involves protein kinase C-delta in lung epithelial cells. Clarke CJ, et al. Mol Pharmacol, 2008 Oct. PMID 18653803, Free PMC Article

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)

Genotypes

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
  

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, ENST00000427130.6
    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

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

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

    Status: REVIEWED

    Source sequence(s)
    AC068522, AC092700

  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_2023_10

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

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

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

Gene LinkOut

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