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NGLY1 N-glycanase 1 [ Homo sapiens (human) ]

Gene ID: 55768, updated on 3-Nov-2024

Summary

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Official Symbol
NGLY1provided by HGNC
Official Full Name
N-glycanase 1provided by HGNC
Primary source
HGNC:HGNC:17646
See related
Ensembl:ENSG00000151092 MIM:610661; AllianceGenome:HGNC:17646
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
CDDG; PNG1; CDG1V; PNG-1; PNGase
Summary
This gene encodes an enzyme that catalyzes hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl) asparagine residue to N-acetyl-beta-D-glucosaminylamine and a peptide containing an aspartate residue. The encoded enzyme may play a role in the proteasome-mediated degradation of misfolded glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]
Expression
Broad expression in testis (RPKM 28.0), lymph node (RPKM 11.3) and 25 other tissues See more
Orthologs
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Genomic context

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See NGLY1 in Genome Data Viewer
Location:
3p24.2
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (25718944..25790039, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (25721799..25792805, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (25760435..25831530, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene DNA topoisomerase II beta Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:25706135-25706698 Neighboring gene microRNA 4442 Neighboring gene cysteine rich protein 1 pseudogene 2 Neighboring gene NANOG hESC enhancer GRCh37_chr3:25793125-25793639 Neighboring gene ribosomal protein L32 pseudogene 11 Neighboring gene TATA-box binding protein associated factor 9b pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19609 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19611 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14147 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:25831060-25831589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19612 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19613 Neighboring gene 3-oxoacyl-ACP synthase, mitochondrial Neighboring gene uncharacterized LOC105377000 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19614

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 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. Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation. Miao X, et al. Nutrients, 2022 Apr 19. PMID 35565658, Free PMC Article
  2. Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway. Enns GM, et al. Genet Med, 2014 Oct. PMID 24651605, Free PMC Article
  3. [Congenital disorder of deglycosylation associated with N-glycanse 1 deficiency]. Lipiński P, et al. Postepy Biochem, 2020 Mar 31. PMID 33320481
  4. NGLY1 deficiency: Novel variants and literature review. Kariminejad A, et al. Eur J Med Genet, 2021 Mar. PMID 33497766
  5. NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy. Caglayan AO, et al. Eur J Med Genet, 2015 Jan. PMID 25220016, Free PMC Article

See all (77) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Structural basis of sugar recognition by SCF[FBS2] ubiquitin ligase involved in NGLY1 deficiency.
    Title: Structural basis of sugar recognition by SCF(FBS2) ubiquitin ligase involved in NGLY1 deficiency.
  2. Ocular features of NGLY1 deficiency from a prospective longitudinal cohort.
    Title: Ocular features of NGLY1 deficiency from a prospective longitudinal cohort.
  3. NGLY1 mutations cause protein aggregation in human neurons.
    Title: NGLY1 mutations cause protein aggregation in human neurons.
  4. N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.
    Title: N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.
  5. NGLY1 deficiency: estimated incidence, clinical features, and genotypic spectrum from the NGLY1 Registry.
    Title: NGLY1 deficiency: estimated incidence, clinical features, and genotypic spectrum from the NGLY1 Registry.
  6. Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells.
    Title: Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells.
  7. Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.
    Title: Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.
  8. Ferroptosis regulation by the NGLY1/NFE2L1 pathway.
    Title: Ferroptosis regulation by the NGLY1/NFE2L1 pathway.
  9. Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.
    Title: Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.
  10. Ever-expanding NGLY1 biology.
    Title: Ever-expanding NGLY1 biology.
Submit: New GeneRIF Correction See all GeneRIFs (27)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of N-glycanase 1 (NGLY1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 is identified to have a physical interaction with N-glycanase 1 (NGLY1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is identified to have a physical interaction with N-glycanase 1 (NGLY1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

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

Clone Names

  • FLJ11005, FLJ12409

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity IGI
Inferred from Genetic Interaction
more info
 PubMed 
enables peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in glycoprotein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glycoprotein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of BMP signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein folding TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase
Names
hPNGase
peptide:N-glycanase
NP_001138765.1
NP_001138766.1
NP_001138767.1
NP_060767.2
XP_005265373.1
XP_005265374.1
XP_011532246.1
XP_016862328.1
XP_047304512.1
XP_047304513.1
XP_047304514.1
XP_047304516.1
XP_047304517.1
XP_054203207.1
XP_054203208.1
XP_054203209.1
XP_054203210.1
XP_054203211.1
XP_054203212.1
XP_054203213.1
XP_054203214.1
XP_054203215.1

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_034108.1 RefSeqGene

    Range
    11597..76096
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001145293.2 → NP_001138765.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 2

    See identical proteins and their annotated locations for NP_001138765.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) includes an alternate exon that causes a frameshift and lacks an alternate exon which restores the reading frame, compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.
    Source sequence(s)
    AC092798, BC000963, BC007226, BQ017148
    Consensus CDS
    CCDS46778.1
    UniProtKB/TrEMBL
    A0A0C4DFP4
    Related
    ENSP00000387430.1, ENST00000428257.5
    Conserved Domains (3) summary
    cd10459
    Location:19 → 109
    PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
    pfam01841
    Location:275 → 334
    Transglut_core; Transglutaminase-like superfamily
    pfam04721
    Location:439 → 633
    PAW; PNGase C-terminal domain, mannose-binding module PAW

  2. NM_001145294.2 → NP_001138766.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 3

    See identical proteins and their annotated locations for NP_001138766.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK296047, BQ017148, DC329733
    Consensus CDS
    CCDS46777.1
    UniProtKB/TrEMBL
    A0A6Q8PF23
    Related
    ENSP00000389888.2, ENST00000417874.6
    Conserved Domains (5) summary
    COG1305
    Location:251 → 312
    YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
    pfam01841
    Location:233 → 312
    Transglut_core; Transglutaminase-like superfamily
    pfam03835
    Location:296 → 349
    Rad4; Rad4 transglutaminase-like domain
    pfam04721
    Location:415 → 609
    PAW; PNGase C-terminal domain, mannose-binding module PAW
    cl15262
    Location:1 → 67
    PUB; PNGase/UBA or UBX (PUB) domain of p97 adaptor proteins

  3. NM_001145295.2 → NP_001138767.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an exon in the 3' coding region, which results in a frameshift and an early stop codon compared to variant 1. The encoded isoform (4) is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC092798, BC007226, BC017220, BQ017148
    Consensus CDS
    CCDS46779.1
    UniProtKB/TrEMBL
    A0A6Q8PF23
    Related
    ENSP00000379886.3, ENST00000396649.7
    Conserved Domains (4) summary
    cd10459
    Location:19 → 109
    PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
    pfam01841
    Location:275 → 354
    Transglut_core; Transglutaminase-like superfamily
    pfam03835
    Location:338 → 392
    Rad4; Rad4 transglutaminase-like domain
    cl10509
    Location:457 → 538
    PAW; PNGase C-terminal domain, mannose-binding module PAW

  4. NM_018297.4 → NP_060767.2  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 1

    See identical proteins and their annotated locations for NP_060767.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC092798, BC007226, BQ017148
    Consensus CDS
    CCDS33719.1
    UniProtKB/Swiss-Prot
    B4DJE9, Q59FB1, Q6PJD8, Q96IV0, Q9BVR8, Q9NR70
    UniProtKB/TrEMBL
    A0A6Q8PF23
    Related
    ENSP00000280700.5, ENST00000280700.10
    Conserved Domains (4) summary
    cd10459
    Location:19 → 109
    PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
    pfam03835
    Location:338 → 391
    Rad4; Rad4 transglutaminase-like domain
    pfam01841
    Location:275 → 354
    Transglut_core; Transglutaminase-like superfamily
    pfam04721
    Location:457 → 651
    PAW; PNGase C-terminal domain, mannose-binding module PAW

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    25718944..25790039 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005265317.1 → XP_005265374.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X6

    Conserved Domains (5) summary
    cd10459
    Location:19 → 109
    PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
    COG1305
    Location:293 → 354
    YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
    pfam01841
    Location:275 → 354
    Transglut_core; Transglutaminase-like superfamily
    pfam03835
    Location:338 → 391
    Rad4; Rad4 transglutaminase-like domain
    cl10509
    Location:416 → 483
    PAW; PNGase C-terminal domain, mannose-binding module PAW

  2. XM_005265316.1 → XP_005265373.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X1

    UniProtKB/TrEMBL
    A0A6Q8PF23
    Conserved Domains (5) summary
    cd10459
    Location:19 → 109
    PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
    COG1305
    Location:293 → 354
    YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
    pfam01841
    Location:275 → 354
    Transglut_core; Transglutaminase-like superfamily
    pfam03835
    Location:338 → 391
    Rad4; Rad4 transglutaminase-like domain
    pfam04721
    Location:416 → 596
    PAW; PNGase C-terminal domain, mannose-binding module PAW

  3. XM_047448558.1 → XP_047304514.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X7

  4. XM_047448556.1 → XP_047304512.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X3

  5. XM_047448557.1 → XP_047304513.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X5

  6. XM_011533944.1 → XP_011532246.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X4

    See identical proteins and their annotated locations for XP_011532246.1

    UniProtKB/TrEMBL
    A0A6Q8PF23
    Related
    ENST00000674841.1
    Conserved Domains (5) summary
    COG1305
    Location:216 → 277
    YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
    pfam01841
    Location:198 → 277
    Transglut_core; Transglutaminase-like superfamily
    pfam03835
    Location:261 → 314
    Rad4; Rad4 transglutaminase-like domain
    pfam04721
    Location:380 → 574
    PAW; PNGase C-terminal domain, mannose-binding module PAW
    cl15262
    Location:1 → 32
    PUB; PNGase/UBA or UBX (PUB) domain of p97 adaptor proteins

  7. XM_017006839.3 → XP_016862328.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X2

    UniProtKB/TrEMBL
    A0A6Q8PF23

  8. XM_047448561.1 → XP_047304517.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X9

  9. XM_047448560.1 → XP_047304516.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X8

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    25721799..25792805 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054347237.1 → XP_054203212.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X6

  2. XM_054347232.1 → XP_054203207.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X1

  3. XM_054347238.1 → XP_054203213.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X7

  4. XM_054347234.1 → XP_054203209.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X3

  5. XM_054347236.1 → XP_054203211.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X5

  6. XM_054347235.1 → XP_054203210.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X4

  7. XM_054347233.1 → XP_054203208.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X2

  8. XM_054347240.1 → XP_054203215.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X9

  9. XM_054347239.1 → XP_054203214.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X8

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_025105.1: Suppressed sequence

    Description
    NM_025105.1: This RefSeq was permanently suppressed because it is primarily intronic sequence.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96IV0.1 GenPept UniProtKB/Swiss-Prot:Q96IV0

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