Human Gene GNE (ENST00000396594.8) from GENCODE V44
  Description: Homo sapiens glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE), transcript variant 1, mRNA. (from RefSeq NM_001128227)
RefSeq Summary (NM_001128227): The protein encoded by this gene is a bifunctional enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. It is a rate-limiting enzyme in the sialic acid biosynthetic pathway. Sialic acid modification of cell surface molecules is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Mutations in this gene are associated with sialuria, autosomal recessive inclusion body myopathy, and Nonaka myopathy. Alternative splicing of this gene results in transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Gencode Transcript: ENST00000396594.8
Gencode Gene: ENSG00000159921.20
Transcript (Including UTRs)
   Position: hg38 chr9:36,214,441-36,276,978 Size: 62,538 Total Exon Count: 12 Strand: -
Coding Region
   Position: hg38 chr9:36,217,365-36,276,944 Size: 59,580 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:36,214,441-36,276,978)mRNA (may differ from genome)Protein (753 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GLCNE_HUMAN
DESCRIPTION: RecName: Full=Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase; AltName: Full=UDP-GlcNAc-2-epimerase/ManAc kinase; Includes: RecName: Full=UDP-N-acetylglucosamine 2-epimerase; EC=5.1.3.14; AltName: Full=UDP-GlcNAc-2-epimerase; AltName: Full=Uridine diphosphate-N-acetylglucosamine-2-epimerase; Includes: RecName: Full=N-acetylmannosamine kinase; EC=2.7.1.60; AltName: Full=ManAc kinase;
FUNCTION: Regulates and initiates biosynthesis of N- acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development (By similarity). Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells.
CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine = UDP-N-acetyl-D- mannosamine.
CATALYTIC ACTIVITY: ATP + N-acyl-D-mannosamine = ADP + N-acyl-D- mannosamine 6-phosphate.
ENZYME REGULATION: Allosterically regulated (Probable); feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP- Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N- acetylmannosamine; the hexamer is fully active for both enzyme activities (By similarity). Up-regulated after PKC-dependent phosphorylation.
PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
SUBUNIT: Homodimer and homohexamer.
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
TISSUE SPECIFICITY: Highest expression in liver and placenta. Also found in heart, brain, lung, kidney, skeletal muscle and pancreas. Isoform 1 is expressed in heart, brain, kidney, liver, placenta, lung, spleen, pancreas, skeletal muscle and colon. Isoform 2 is expressed mainly in placenta, but also in brain, kidney, liver, lung, pancreas and colon. Isoform 3 is expressed at low level in kidney, liver, placenta and colon.
PTM: Phosphorylated by PKC (By similarity).
DISEASE: Defects in GNE are a cause of sialuria (SIALURIA) [MIM:269921]; also known as sialuria French type. In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant.
DISEASE: Defects in GNE are the cause of inclusion body myopathy type 2 (IBM2) [MIM:600737]. Hereditary inclusion body myopathies are a group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. IBM2 is an autosomal recessive disorder affecting mainly leg muscles, but with an unusual distribution that spares the quadriceps as also observed in Nonaka myopathy.
DISEASE: Defects in GNE are the cause of Nonaka myopathy (NM) [MIM:605820]; also known as distal myopathy with rimmed vacuoles (DMRV). NM is an autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens.
SIMILARITY: In the N-terminal section; belongs to the UDP-N- acetylglucosamine 2-epimerase family.
SIMILARITY: In the C-terminal section; belongs to the ROK (NagC/XylR) family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GNE";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: GNE
Diseases sorted by gene-association score: sialuria* (1709), nonaka myopathy* (1264), inclusion body myositis* (778), gne-related myopathy* (500), oculopharyngodistal myopathy (18), distal muscular dystrophy (18), myopathy (17), free sialic acid storage disorders (14), laryngeal tuberculosis (11), inclusion body myopathy with paget disease of bone and frontotemporal dementia (7), myositis (7), myopathy, x-linked, with excessive autophagy (7), neuromuscular disease (6), muscular dystrophy-dystroglycanopathy , type b, 6 (5), muscle tissue disease (5), bardet-biedl syndrome 2 (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D008727 Methotrexate
  • D013749 Tetrachlorodibenzodioxin
  • C006253 pirinixic acid
  • C049325 1,2-dithiol-3-thione
  • C495626 14-deoxy-11,12-didehydroandrographolide
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C028451 3,4,3',4'-tetrachlorobiphenyl
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • D000082 Acetaminophen
  • D000643 Ammonium Chloride
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.97 RPKM in Liver
Total median expression: 286.08 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -5.6034-0.165 Picture PostScript Text
3' UTR -1094.602924-0.374 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001312 - Hexokinase
IPR000600 - ROK
IPR020004 - UDP-GlcNAc_Epase
IPR003331 - UDP_GlcNAc_Epimerase_2

Pfam Domains:
PF02350 - UDP-N-acetylglucosamine 2-epimerase
PF00480 - ROK family

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2YHW - X-ray MuPIT 2YHY - X-ray MuPIT 2YI1 - X-ray MuPIT 3EO3 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9Y223
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008761 UDP-N-acetylglucosamine 2-epimerase activity
GO:0009384 N-acylmannosamine kinase activity
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0016787 hydrolase activity
GO:0046872 metal ion binding

Biological Process:
GO:0006045 N-acetylglucosamine biosynthetic process
GO:0006047 UDP-N-acetylglucosamine metabolic process
GO:0006054 N-acetylneuraminate metabolic process
GO:0007155 cell adhesion
GO:0008152 metabolic process
GO:0016310 phosphorylation
GO:0046835 carbohydrate phosphorylation

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  LP895623 - Sequence 487 from Patent EP3253886.
AJ238764 - Homo sapiens mRNA for UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase.
AY531126 - Homo sapiens isolate Y7303-49 UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase (GNE) mRNA, complete cds.
AY531127 - Homo sapiens isolate Y9103-50 UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase (GNE) mRNA, complete cds.
AY531128 - Homo sapiens isolate W7803-30 UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase (GNE) mRNA, complete cds.
JD353254 - Sequence 334278 from Patent EP1572962.
JD238677 - Sequence 219701 from Patent EP1572962.
JD468958 - Sequence 449982 from Patent EP1572962.
JD499900 - Sequence 480924 from Patent EP1572962.
JD383609 - Sequence 364633 from Patent EP1572962.
JD545236 - Sequence 526260 from Patent EP1572962.
JD280083 - Sequence 261107 from Patent EP1572962.
JD119351 - Sequence 100375 from Patent EP1572962.
AK299488 - Homo sapiens cDNA FLJ58375 complete cds, moderately similar to Bifunctional UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase.
JD189755 - Sequence 170779 from Patent EP1572962.
JD405164 - Sequence 386188 from Patent EP1572962.
JD461260 - Sequence 442284 from Patent EP1572962.
JD537878 - Sequence 518902 from Patent EP1572962.
JD558947 - Sequence 539971 from Patent EP1572962.
JD179694 - Sequence 160718 from Patent EP1572962.
JD481352 - Sequence 462376 from Patent EP1572962.
JD481351 - Sequence 462375 from Patent EP1572962.
JD246857 - Sequence 227881 from Patent EP1572962.
JD413346 - Sequence 394370 from Patent EP1572962.
JD324245 - Sequence 305269 from Patent EP1572962.
JD198056 - Sequence 179080 from Patent EP1572962.
JD173985 - Sequence 155009 from Patent EP1572962.
JD212677 - Sequence 193701 from Patent EP1572962.
JD118367 - Sequence 99391 from Patent EP1572962.
JD393237 - Sequence 374261 from Patent EP1572962.
JD522462 - Sequence 503486 from Patent EP1572962.
JD351482 - Sequence 332506 from Patent EP1572962.
AK296687 - Homo sapiens cDNA FLJ52319 complete cds, highly similar to Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.
JD310451 - Sequence 291475 from Patent EP1572962.
JD281905 - Sequence 262929 from Patent EP1572962.
JD337406 - Sequence 318430 from Patent EP1572962.
AK295562 - Homo sapiens cDNA FLJ51479 complete cds, highly similar to Bifunctional UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase.
EU093084 - Homo sapiens isolate GNE-1 mutant UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase mRNA, complete cds, alternatively spliced.
BC121179 - Homo sapiens glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase, mRNA (cDNA clone MGC:150583 IMAGE:40122902), complete cds.
JD301018 - Sequence 282042 from Patent EP1572962.
AF051852 - Homo sapiens UDP-N-acetylglucosamine-2-epimerase mRNA, complete cds.
JD236399 - Sequence 217423 from Patent EP1572962.
JD181071 - Sequence 162095 from Patent EP1572962.
JD173213 - Sequence 154237 from Patent EP1572962.
JD240546 - Sequence 221570 from Patent EP1572962.
AF155663 - Homo sapiens UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase mRNA, complete cds.
AM697709 - Homo sapiens mRNA for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE gene), GNE3 isoform.
AM697708 - Homo sapiens mRNA for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE gene), putative GNE1 and GNE2 isoforms.
AK312539 - Homo sapiens cDNA, FLJ92908, Homo sapiensUDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase(GNE), mRNA.
KJ892899 - Synthetic construct Homo sapiens clone ccsbBroadEn_02293 GNE gene, encodes complete protein.
KR711940 - Synthetic construct Homo sapiens clone CCSBHm_00032504 GNE (GNE) mRNA, encodes complete protein.
KR711941 - Synthetic construct Homo sapiens clone CCSBHm_00032513 GNE (GNE) mRNA, encodes complete protein.
KR711942 - Synthetic construct Homo sapiens clone CCSBHm_00032524 GNE (GNE) mRNA, encodes complete protein.
KR711943 - Synthetic construct Homo sapiens clone CCSBHm_00032537 GNE (GNE) mRNA, encodes complete protein.
DQ591819 - Homo sapiens piRNA piR-58931, complete sequence.
JD562813 - Sequence 543837 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00520 - Amino sugar and nucleotide sugar metabolism
hsa01100 - Metabolic pathways

BioCyc Knowledge Library
PWY-6138 - CMP-N-acetylneuraminate biosynthesis I (eukaryotes)

Reactome (by CSHL, EBI, and GO)

Protein Q9Y223 (Reactome details) participates in the following event(s):

R-HSA-4085028 GNE phosphorylates ManNAc to ManNAc-6-P
R-HSA-4085021 GNE hydrolyzes/epimerises UDP-GlcNAc to ManNAc and UDP
R-HSA-4085001 Sialic acid metabolism
R-HSA-446219 Synthesis of substrates in N-glycan biosythesis
R-HSA-446193 Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203 Asparagine N-linked glycosylation
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A6PZH2, A6PZH3, A7UNU7, B2R6E1, B7Z372, D3DRP7, ENST00000396594.1, ENST00000396594.2, ENST00000396594.3, ENST00000396594.4, ENST00000396594.5, ENST00000396594.6, ENST00000396594.7, F5H499, GLCNE, GLCNE_HUMAN, NM_001128227, Q0VA94, Q9Y223, uc010mli.1, uc010mli.2, uc010mli.3, uc010mli.4, uc010mli.5
UCSC ID: ENST00000396594.8
RefSeq Accession: NM_001128227
Protein: Q9Y223 (aka GLCNE_HUMAN or GLNE_HUMAN)
CCDS: CCDS6602.1, CCDS47965.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene GNE:
ibm (GNE Myopathy)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.