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

• 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: 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;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (41 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3;Autosomal recessive limb-girdle muscular dystrophy type 2O (16 variants)
• Muscle eye brain disease (11 variants)
• not provided (8 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (8 variants)
• Muscular dystrophy-dystroglycanopathy (5 variants)
• Retinitis pigmentosa 76 (4 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2O (4 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (3 variants)
• Hydrocephalus (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy (1 variants)
• Abnormality of the nervous system (1 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3;Autosomal recessive limb-girdle muscular dystrophy type 2O;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3;Retinitis pigmentosa 76 (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.

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	1		9	253	1	264
missense	1	20	355	4	1	381
nonsense	20	25	1			46
start loss	2					2
frameshift	35	48	2			85
inframe indel			6			6
splice donor/acceptor (+/-2bp)	3	52	1			56
splice region		2	38	88	1	129
non coding			21	232	19	272
Total	62	145	395	489	21

Highest pathogenic variant AF is 0.0000460

Variants in POMGNT1

This is a list of pathogenic ClinVar variants found in the POMGNT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-46188719-T-C		Retinal dystrophy	Likely benign (Oct 01, 2023)
1-46188739-G-A		Muscle eye brain disease	Uncertain significance (Aug 08, 2017)
1-46188756-AG-A		Muscle eye brain disease	Uncertain significance (Oct 25, 2017)
1-46188768-G-A			Uncertain significance (Mar 11, 2022)
1-46188770-C-T		Muscle eye brain disease	Uncertain significance (Jan 30, 2017)
1-46188771-C-T		Muscle eye brain disease	Uncertain significance (Nov 02, 2017)
1-46188813-G-A		Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 • Retinitis pigmentosa 76 • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 • Autosomal recessive limb-girdle muscular dystrophy type 2O	Uncertain significance (Jul 22, 2021)
1-46188819-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2O • Congenital Muscular Dystrophy, alpha-dystroglycan related	Conflicting classifications of pathogenicity (Oct 18, 2021)
1-46188864-G-GCC		Muscle eye brain disease	Uncertain significance (Dec 04, 2017)
1-46188908-CAGGCCCTCCAGGTTCGGCCTGTTTTCA-C		Muscle eye brain disease	Uncertain significance (Apr 29, 2018)
1-46188923-C-T			Likely benign (Jul 01, 2022)
1-46188968-T-C		POMGNT1-related disorder	Likely benign (Jun 07, 2019)
1-46188975-C-T		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
1-46189049-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2O • Congenital Muscular Dystrophy, alpha-dystroglycan related	Conflicting classifications of pathogenicity (Jul 17, 2018)
1-46189063-C-T		Congenital Muscular Dystrophy, alpha-dystroglycan related • Autosomal recessive limb-girdle muscular dystrophy type 2O	Uncertain significance (Jan 13, 2018)
1-46189236-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2O • Congenital Muscular Dystrophy, alpha-dystroglycan related • POMGNT1-related disorder	Conflicting classifications of pathogenicity (Nov 01, 2023)
1-46189236-CAGTA-C		Muscle eye brain disease	Uncertain significance (Apr 06, 2018)
1-46189258-CT-C		Autism spectrum disorder	Uncertain significance (Apr 20, 2020)
1-46189259-TGGA-T		Muscle eye brain disease	Uncertain significance (Nov 08, 2017)
1-46189268-T-A		Muscle eye brain disease	Uncertain significance (-)
1-46189273-T-G		Autosomal recessive limb-girdle muscular dystrophy type 2O;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	Likely benign (Dec 14, 2021)
1-46189274-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2O;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 • Muscle eye brain disease	Uncertain significance (Jul 26, 2022)
1-46189276-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2O;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	Likely benign (Mar 15, 2023)
1-46189278-G-A		POMGNT1-related disorder • Autosomal recessive limb-girdle muscular dystrophy type 2O;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	Uncertain significance (May 06, 2022)
1-46189278-G-GTTCTGGGGC		Muscle eye brain disease	Uncertain significance (Apr 05, 2018)

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
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: 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

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