POMGNT1

protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-), the group of O-linked N-acetylglucosaminyltransferases

Basic information

Region (hg38): 1:46188683-46220305

Previous symbols: [ "MEB" ]

Links

ENSG00000085998 ∙ NCBI:55624 ∙ OMIM:606822 ∙ HGNC:19139 ∙ Uniprot:Q8WZA1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2O (Limited), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (Limited), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (Definitive), mode of inheritance: AR
• retinitis pigmentosa 76 (Limited), mode of inheritance: AR
• myopathy caused by variation in POMGNT1 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (Strong), mode of inheritance: AR
• retinitis pigmentosa 76 (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (Strong), mode of inheritance: AR
• muscle-eye-brain disease (Definitive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
• muscle-eye-brain disease (Supportive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2O (Supportive), mode of inheritance: AR
• congenital muscular dystrophy with cerebellar involvement (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2O (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 3; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3; Retinitis pigmentosa 76	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	11709191; 12588800; 15236414; 17030669; 17878207; 19067344; 19299310; 26908613; 27391550

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POMGNT1 gene.

• Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2O (1184 variants)
• Muscular_dystrophy-dystroglycanopathy_(congenital_with_intellectual_disability),_type_B3 (1180 variants)
• not_provided (274 variants)
• Muscle_eye_brain_disease (226 variants)
• Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A3 (195 variants)
• Inborn_genetic_diseases (100 variants)
• Retinitis_pigmentosa_76 (82 variants)
• not_specified (74 variants)
• Muscular_dystrophy-dystroglycanopathy (58 variants)
• Retinal_dystrophy (40 variants)
• Congenital_Muscular_Dystrophy,_alpha-dystroglycan_related (32 variants)
• POMGNT1-related_disorder (27 variants)
• Autosomal_recessive_limb-girdle_muscular_dystrophy (10 variants)
• Myopathy_caused_by_variation_in_POMGNT1 (5 variants)
• Retinitis_pigmentosa (3 variants)
• Abnormality_of_the_nervous_system (2 variants)
• Hydrocephalus (1 variants)
• Intellectual_disability (1 variants)
• Muscular_dystrophy-dystroglycanopathy_type_B6 (1 variants)
• Hypotonia (1 variants)
• Structural_eye_disease (1 variants)
• Phenylketonuria (1 variants)
• Optic_atrophy (1 variants)
• Limb-girdle_muscular_dystrophy (1 variants)
• Congenital_muscular_alpha-dystroglycanopathy_with_brain_and_eye_anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMGNT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017739.4. 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	1	1	21	313		336
missense	6	42	421	14		483
nonsense	25	27	1			53
start loss	2					2
frameshift	41	67	1			109
splice donor/acceptor (+/-2bp)	6	63	10			79
Total	81	200	454	327	0

Highest pathogenic variant AF is 0.00035324038

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMGNT1	protein_coding	protein_coding	ENST00000371992	22	31624

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125507	0	241	125748	0.000959

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.899	373	425	0.877	0.0000263	4886
Missense in Polyphen		112	137.45	0.81487		1580
Synonymous	-0.240	163	159	1.02	0.00000899	1485
Loss of Function	1.32	36	45.6	0.789	0.00000274	487

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000784	0.000767
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000761	0.000761
Finnish	0.00213	0.00213
European (Non-Finnish)	0.00120	0.00120
Middle Eastern	0.000761	0.000761
South Asian	0.000557	0.000555
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216). Catalyzes the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins, providing the necessary basis for the addition of further carbohydrate moieties (PubMed:11709191, PubMed:27493216). Is specific for alpha linked terminal mannose and does not have MGAT3, MGAT4, MGAT5, MGAT7 or MGAT8 activity. {ECO:0000269|PubMed:11709191, ECO:0000269|PubMed:11742540, ECO:0000269|PubMed:26908613, ECO:0000269|PubMed:27391550, ECO:0000269|PubMed:27493216}.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3) [MIM:253280]: An autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, cobblestone lissencephaly, and cerebellar and pontine hypoplasia. Patients present severe congenital myopia, congenital glaucoma, pallor of the optic disks, retinal hypoplasia, mental retardation, hydrocephalus, abnormal electroencephalograms, generalized muscle weakness and myoclonic jerks. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:11709191, ECO:0000269|PubMed:12588800, ECO:0000269|PubMed:12788071, ECO:0000269|PubMed:15207699, ECO:0000269|PubMed:15236414, ECO:0000269|PubMed:15466003, ECO:0000269|PubMed:17030669, ECO:0000269|PubMed:19067344}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy congenital with mental retardation B3 (MDDGB3) [MIM:613151]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with mental retardation and mild structural brain abnormalities. Clinical features include mental retardation, white matter changes, cerebellar cysts, pontine hypoplasia, myopia, optic atrophy, decreased alpha-dystroglycan on muscle biopsy and increased serum creatine kinase. {ECO:0000269|PubMed:17030669, ECO:0000269|PubMed:19067344, ECO:0000269|PubMed:19299310}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C3 (MDDGC3) [MIM:613157]: A rare form of limb-girdle muscular dystrophy with normal cognition. Muscle biopsy shows dystrophic changes with variable staining for glycosylated alpha- dystroglycan. {ECO:0000269|PubMed:18195152}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 76 (RP76) [MIM:617123]: A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP76 inheritance is autosomal recessive. {ECO:0000269|PubMed:26908613, ECO:0000269|PubMed:27391550}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mannose type O-glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.301

Intolerance Scores

• loftool: 0.459
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.47

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.175

Gene Damage Prediction

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

Gene ontology

• Biological process: protein O-linked glycosylation;O-glycan processing
• Cellular component: Golgi membrane;integral component of membrane;integral component of Golgi membrane
• Molecular function: protein binding;acetylglucosaminyltransferase activity;manganese ion binding;beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity