GNPTAB

N-acetylglucosamine-1-phosphate transferase subunits alpha and beta, the group of EF-hand domain containing

Basic information

Region (hg38): 12:101745498-101830959

Previous symbols: [ "GNPTA" ]

Links

ENSG00000111670 ∙ NCBI:79158 ∙ OMIM:607840 ∙ HGNC:29670 ∙ Uniprot:Q3T906 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucolipidosis (Definitive), mode of inheritance: AR
• mucolipidosis type III, alpha/beta (Definitive), mode of inheritance: AR
• mucolipidosis type II (Strong), mode of inheritance: AR
• mucolipidosis type II (Strong), mode of inheritance: AR
• mucolipidosis type III, alpha/beta (Strong), mode of inheritance: AR
• mucolipidosis type III, alpha/beta (Definitive), mode of inheritance: AR
• mucolipidosis type II (Definitive), mode of inheritance: AR
• mucolipidosis type II (Supportive), mode of inheritance: AR
• mucolipidosis type III, alpha/beta (Supportive), mode of inheritance: AR
• mucolipidosis type II (Strong), mode of inheritance: AR
• GNPTAB-mucolipidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucolipidosis III alpha/beta (Pseudo-Hurler polydstrophy); Mucolipidosis II alpha/beta (I-cell disease)	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; Neurologic	4958870; 4247489; 4327936; 6461005; 6309902; 3003148; 3001079; 7628121; 12705498; 16116615; 15633164; 16094673; 16630736; 19197337; 19659762; 20301728; 21416587; 22162509; 22495880
Bisphosphonate therapy may be beneficial for bone pain; The conditions may include severe cardiac manifestations

ClinVar

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

• Mucolipidosis type II;Pseudo-Hurler polydystrophy (874 variants)
• Mucolipidosis type II (297 variants)
• Pseudo-Hurler polydystrophy (163 variants)
• not provided (142 variants)
• Pseudo-Hurler polydystrophy;Mucolipidosis type II (56 variants)
• Inborn genetic diseases (39 variants)
• not specified (38 variants)
• Mucolipidosis (27 variants)
• Mucolipidosis, Type III Alpha/Beta (9 variants)
• - (5 variants)
• Mucopolysaccharidosis, MPS-III-A (5 variants)
• GNPTAB-Related Disorders (4 variants)
• GNPTAB-related condition (3 variants)
• Abnormality of metabolism/homeostasis (2 variants)
• GNPTAB-related disorder (2 variants)
• Legg-Calve-Perthes disease;Juvenile osteochondrosis of spine (1 variants)
• Mucolipidosis III alpha/beta, atypical (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNPTAB gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	311	7	322
missense	5	21	198	20		244
nonsense	38	40	1			79
start loss	2					2
frameshift	80	59				139
inframe indel		1	14			15
splice donor/acceptor (+/-2bp)	4	26	2	1		33
splice region	1	3	17	55	4	80
non coding	1	1	34	77	41	154
Total	130	148	253	409	48

Highest pathogenic variant AF is 0.000355

Variants in GNPTAB

This is a list of pathogenic ClinVar variants found in the GNPTAB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-101745531-AG-A		Mucolipidosis, Type III Alpha/Beta • Mucolipidosis type II	Uncertain significance (Jun 14, 2016)
12-101745614-G-T		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Jan 12, 2018)
12-101745700-T-C		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Jan 13, 2018)
12-101745707-T-C		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Benign (Jan 12, 2018)
12-101745774-C-G		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Jan 12, 2018)
12-101745794-G-A		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Jan 12, 2018)
12-101745921-G-A		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101745924-A-G		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Benign (Jan 13, 2018)
12-101745931-A-C		Mucolipidosis, Type III Alpha/Beta • Mucolipidosis type II	Uncertain significance (Jun 14, 2016)
12-101745969-T-G		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Benign (Jan 12, 2018)
12-101746004-C-T		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101746034-A-AAAC		Mucolipidosis type II • Mucolipidosis, Type III Alpha/Beta	Likely benign (Jun 14, 2016)
12-101746055-C-A		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Jan 13, 2018)
12-101746071-G-C		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Jan 12, 2018)
12-101746131-G-C		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101746244-C-T		Mucolipidosis type II • Mucolipidosis, Type III Alpha/Beta	Uncertain significance (Jun 14, 2016)
12-101746253-T-C		Pseudo-Hurler polydystrophy • Mucolipidosis type II	Uncertain significance (Mar 23, 2018)
12-101746272-C-CCT		Mucolipidosis type II • Mucolipidosis, Type III Alpha/Beta	Likely benign (Jun 14, 2016)
12-101746322-A-C		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101746325-G-A		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101746350-A-C		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Benign (Jan 13, 2018)
12-101746425-A-G		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101746518-C-A		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Uncertain significance (Jan 12, 2018)
12-101746552-A-G		Mucolipidosis type II • Pseudo-Hurler polydystrophy	Benign (Jan 13, 2018)
12-101746605-AT-A		Mucolipidosis, Type III Alpha/Beta • Mucolipidosis type II	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNPTAB	protein_coding	protein_coding	ENST00000299314	21	85442

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.68e-19	0.984	125384	0	364	125748	0.00145

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	572	658	0.870	0.0000339	8375
Missense in Polyphen		209	277.35	0.75357		3504
Synonymous	-0.702	259	245	1.06	0.0000135	2314
Loss of Function	2.71	39	62.0	0.629	0.00000335	738

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00387	0.00337
Ashkenazi Jewish	0.00	0.00
East Asian	0.000816	0.000816
Finnish	0.00282	0.00282
European (Non-Finnish)	0.00136	0.00136
Middle Eastern	0.000816	0.000816
South Asian	0.00147	0.00147
Other	0.00163	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. M6P residues are required to bind to the M6P receptors (MPR), which mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment. {ECO:0000269|PubMed:19955174, ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:28918368}.
• Disease: DISEASE: Mucolipidosis type II (MLII) [MIM:252500]: Fatal, autosomal recessive, lysosomal storage disorder characterized by severe clinical and radiologic features, peculiar fibroblast inclusions, and no excessive mucopolysacchariduria. Congenital dislocation of the hip, thoracic deformities, hernia, and hyperplastic gums are evident soon after birth. {ECO:0000269|PubMed:16200072, ECO:0000269|PubMed:16835905, ECO:0000269|PubMed:19197337, ECO:0000269|PubMed:19617216, ECO:0000269|PubMed:19634183, ECO:0000269|PubMed:19938078, ECO:0000269|PubMed:22495880, ECO:0000269|PubMed:23566849, ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:23773965, ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:24798265, ECO:0000269|PubMed:25505245, ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mucolipidosis type III complementation group A (MLIIIA) [MIM:252600]: Autosomal recessive disease of lysosomal enzyme targeting. Clinically MLIII is characterized by restricted joint mobility, skeletal dysplasia, and short stature. Mildly coarsened facial features and thickening of the skin have been described. Cardiac valvular disease and corneal clouding may also occur. Half of the reported patients show learning disabilities or mental retardation. {ECO:0000269|PubMed:16094673, ECO:0000269|PubMed:16465621, ECO:0000269|PubMed:16630736, ECO:0000269|PubMed:17034777, ECO:0000269|PubMed:19197337, ECO:0000269|PubMed:19617216, ECO:0000269|PubMed:19634183, ECO:0000269|PubMed:19938078, ECO:0000269|PubMed:23566849, ECO:0000269|PubMed:24045841, ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:24550498, ECO:0000269|PubMed:25505245, ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Genetic variations in GNPTAB 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: 0.149

Intolerance Scores

• loftool: 0.0896
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.51

Haploinsufficiency Scores

• pHI: 0.705
• hipred: N
• hipred_score: 0.414
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.433

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnptab
• Phenotype: respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: gnptab
• Affected structure: osteoblast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: lysosome organization;N-glycan processing to lysosome;secretion of lysosomal enzymes;carbohydrate phosphorylation
• Cellular component: Golgi membrane;Golgi apparatus;integral component of membrane
• Molecular function: UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity;calcium ion binding;protein binding