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
Phenotypes
GenCC
Source:
- muscle-eye-brain disease (Definitive), 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 brain and eye anomalies), type A3 (Strong), mode of inheritance: AR
- 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
- 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 intellectual disability), type B3 (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
- myopathy caused by variation in POMGNT1 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2O (1160 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_intellectual_disability),_type_B3 (1157 variants)
- not_provided (267 variants)
- Muscle_eye_brain_disease (226 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A3 (195 variants)
- Inborn_genetic_diseases (94 variants)
- Retinitis_pigmentosa_76 (79 variants)
- not_specified (72 variants)
- Muscular_dystrophy-dystroglycanopathy (58 variants)
- Retinal_dystrophy (40 variants)
- Congenital_Muscular_Dystrophy,_alpha-dystroglycan_related (33 variants)
- POMGNT1-related_disorder (26 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)
- Limb-girdle_muscular_dystrophy,_recessive (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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 21 | 306 | 329 | |||
| missense | 42 | 412 | 14 | 474 | ||
| nonsense | 25 | 27 | 53 | |||
| start loss | 2 | 2 | ||||
| frameshift | 40 | 67 | 108 | |||
| splice donor/acceptor (+/-2bp) | 63 | 71 | ||||
| Total | 80 | 200 | 437 | 320 | 0 |
Highest pathogenic variant AF is 0.00035324
Loading clinvar variants...
GnomAD
Source:
| 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 |
|---|---|---|---|---|---|---|
| 1.95e-20 | 0.0825 | 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:
- 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
Haploinsufficiency Scores
- pHI
- 0.529
- hipred
- N
- hipred_score
- 0.426
- ghis
- 0.551
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 |
Mouse Genome Informatics
- Gene name
- Pomgnt1
- 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye 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); muscle phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype;
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