NAGPA N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase [Homo sapiens (human)] - Gene

Summary

Official Symbol: NAGPAprovided by HGNC
Official Full Name: N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidaseprovided by HGNC
Primary source: HGNC:HGNC:17378
See related: Ensembl:ENSG00000103174 MIM:607985; AllianceGenome:HGNC:17378
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: UCE; APAA
Summary: Hydrolases are transported to lysosomes after binding to mannose 6-phosphate receptors in the trans-Golgi network. This gene encodes the enzyme that catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal hydrolases. Commonly known as 'uncovering enzyme' or UCE, this enzyme removes N-acetyl-D-glucosamine (GlcNAc) residues from GlcNAc-alpha-P-mannose moieties and thereby produces the recognition marker. The encoded preproprotein is proteolytically processed by furin to generate the mature enzyme, a homotetramer of two disulfide-linked homodimers. Mutations in this gene are associated with developmental stuttering in human patients. [provided by RefSeq, Oct 2015]
Expression: Ubiquitous expression in spleen (RPKM 5.3), stomach (RPKM 4.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p13.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (5024844..5033935, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (5054343..5063428, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (5074845..5083936, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis.
Title: Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis.
Crystal Structure of the Mannose-6-Phosphate Uncovering Enzyme.
Title: Crystal Structure of the Mannose-6-Phosphate Uncovering Enzyme.
We evaluated 51 stuttering individuals with a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant.
Title: Genetic factors and therapy outcomes in persistent developmental stuttering.
14 variations were found in GNPTAB, GNPTG and NAGPA genes.
Title: Variants in GNPTAB, GNPTG and NAGPA genes are associated with stutterers.
SNPs covering GNPTAB, GNPTG and NAGPA were subjected to genotyping, association analysis was performed on all SNPs. Significant association of rs17031962 in GNPTAB and rs882294 in NAGPA with developmental dyslexia in a Chinese population was identified after false discovery rate correction for multiple comparisons.
Title: Association study of stuttering candidate genes GNPTAB, GNPTG and NAGPA with dyslexia in Chinese population.
Mutational analysis of several residues in a highly conserved surface cavity of hUCE revealed that they are essential for function.
Title: Structure and function of the DUF2233 domain in bacteria and in the human mannose 6-phosphate uncovering enzyme.
To date mutations in GNPTAB, GNPTG, and NAGPA have been associated with stuttering. These genes encode the lysosomal enzyme targeting pathway, defective in mucolipidosis. (Review)
Title: A role for inherited metabolic deficits in persistent developmental stuttering.
Analysis of mannose 6-phosphate uncovering enzyme mutations associated with persistent stuttering.
Title: Analysis of mannose 6-phosphate uncovering enzyme mutations associated with persistent stuttering.
identified three mutations in the NAGPA gene associated with stuttering
Title: Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.
The mannose 6-phosphate uncovering enzyme participates in the uncovering of the mannose 6-phosphate recognition tag on lysosomal enzymes, a process that facilitates recognition of those enzymes by mannose 6-phosphate receptors to delivery to lysosomes.
Title: Characterization of the TGN exit signal of the human mannose 6-phosphate uncovering enzyme.

Submit: New GeneRIF Correction See all GeneRIFs (11)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:9484

RH64906 (e-PCR)
- UniSTS:86405

SHGC-67307 (e-PCR)
- UniSTS:89991

RH80883 (e-PCR)
- UniSTS:92817

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in carbohydrate metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in lysosome organization	TAS Traceable Author Statement more info	PubMed
involved_in protein glycosylation	IEA Inferred from Electronic Annotation more info
involved_in protein modification process	TAS Traceable Author Statement more info	PubMed
involved_in protein targeting to lysosome	TAS Traceable Author Statement more info	PubMed
involved_in secretion of lysosomal enzymes	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in Golgi cisterna membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase

Names: alpha-N-acetylglucosaminyl phosphodiesterase; lysosomal alpha-N-acetylglucosaminidase; mannose 6-phosphate-uncovering enzyme; phosphodiester alpha-GlcNAcase

NP_057340.2

EC 3.1.4.45

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.