GNPTG

N-acetylglucosamine-1-phosphate transferase subunit gamma, the group of MRH domain containing

Basic information

Region (hg38): 16:1351931-1365737

Previous symbols: [ "GNPTAG", "C16orf27" ]

Links

ENSG00000090581 ∙ NCBI:84572 ∙ OMIM:607838 ∙ HGNC:23026 ∙ Uniprot:Q9UJJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• GNPTG-mucolipidosis (Definitive), mode of inheritance: AR
• GNPTG-mucolipidosis (Definitive), mode of inheritance: AR
• GNPTG-mucolipidosis (Strong), mode of inheritance: AR
• GNPTG-mucolipidosis (Strong), mode of inheritance: AR
• GNPTG-mucolipidosis (Supportive), mode of inheritance: AR
• GNPTG-mucolipidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucolipidosis III gamma	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Musculoskeletal	10712439; 15532026; 19370764; 19659762; 20034096; 20951619; 21792934
The condition may include severe cardiac manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNPTG gene.

• not_provided (831 variants)
• GNPTG-mucolipidosis (252 variants)
• Inborn_genetic_diseases (55 variants)
• not_specified (15 variants)
• GNPTG-related_disorder (15 variants)
• Retinal_dystrophy (5 variants)
• Mucolipidosis (2 variants)
• Rod-cone_dystrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNPTG gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032520.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	241	1	248
missense		4	216	11	2	233
nonsense	21	9	4			34
start loss			3			3
frameshift	46	14	21			81
splice donor/acceptor (+/-2bp)	12	32	1		1	46
Total	79	59	251	252	4

Highest pathogenic variant AF is 0.000164831

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNPTG	protein_coding	protein_coding	ENST00000204679	11	11429

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.63e-9	0.374	125651	0	97	125748	0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.06	253	176	1.44	0.0000120	1960
Missense in Polyphen		64	49.319	1.2977		581
Synonymous	-4.86	132	77.6	1.70	0.00000586	582
Loss of Function	0.853	15	19.0	0.789	0.00000102	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000911	0.000908
Ashkenazi Jewish	0.000895	0.000893
East Asian	0.0000544	0.0000544
Finnish	0.000284	0.000277
European (Non-Finnish)	0.000450	0.000448
Middle Eastern	0.0000544	0.0000544
South Asian	0.000262	0.000261
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-catalytic subunit of the N-acetylglucosamine-1- phosphotransferase complex, an enzyme that catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. Binds and presents the high mannose glycans of the acceptor to the catalytic alpha and beta subunits (GNPTAB). Enhances the rate of N-acetylglucosamine- 1-phosphate transfer to the oligosaccharides of acid hydrolase acceptors. {ECO:0000269|PubMed:10712439, ECO:0000269|PubMed:19955174}.
• Disease: DISEASE: Mucolipidosis type III complementation group C (MLIIIC) [MIM:252605]: Autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (GlcNAc- phosphotransferase) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Typical clinical findings include stiffness of the hands and shoulders, claw-hand deformity, scoliosis, short stature, coarse facies, and mild mental retardation. Radiographically, severe dysostosis multiplex of the hip is characteristic and frequently disabling. The clinical diagnosis can be confirmed by finding elevated serum lysosomal enzyme levels and/or decreased lysosomal enzyme levels in cultured fibroblasts. {ECO:0000269|PubMed:10712439, ECO:0000269|PubMed:15060128, ECO:0000269|PubMed:15532026, ECO:0000269|PubMed:19370764, ECO:0000269|PubMed:24316125, ECO:0000269|PubMed:26108976, ECO:0000269|PubMed:27038293}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in GNPTG have been suggested to play a role in susceptibility to persistent stuttering. Stuttering is a common speech disorder characterized by repetitions, prolongations, and interruptions in the flow of speech. {ECO:0000269|PubMed:20147709}.
• Pathway: Lysosome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.331
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.7

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.204
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.819

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gnptg
• Phenotype: homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: gnptg
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased life span

Gene ontology

• Biological process: N-glycan processing to lysosome;carbohydrate phosphorylation
• Cellular component: Golgi membrane;Golgi apparatus;extracellular exosome
• Molecular function: UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity;protein homodimerization activity