POMT2

protein O-mannosyltransferase 2, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases

Basic information

Region (hg38): 14:77274955-77320883

Links

ENSG00000009830 ∙ NCBI:29954 ∙ OMIM:607439 ∙ HGNC:19743 ∙ Uniprot:Q9UKY4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (Moderate), mode of inheritance: AR
• 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 2N (Supportive), mode of inheritance: AR
• congenital muscular dystrophy with cerebellar involvement (Supportive), mode of inheritance: AR
• congenital muscular dystrophy with intellectual disability (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (Strong), mode of inheritance: AR
• myopathy caused by variation in POMT2 (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, 2 ; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C 2	AR	Cardiovascular	Conditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical management	Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	15894594; 16701995; 17923109; 17878207; 19067344; 19299310; 19138766; 20301468; 20816175; 22727687

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POMT2 gene.

• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Autosomal recessive limb-girdle muscular dystrophy type 2N (447 variants)
• not provided (334 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2N (132 variants)
• not specified (86 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (62 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (56 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (50 variants)
• Inborn genetic diseases (26 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (25 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Autosomal recessive limb-girdle muscular dystrophy type 2N (12 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (10 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (10 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;Autosomal recessive limb-girdle muscular dystrophy type 2N (7 variants)
• Limb-Girdle Muscular Dystrophy, Recessive (6 variants)
• Autosomal recessive limb-girdle muscular dystrophy (5 variants)
• Muscular dystrophy (3 variants)
• POMT2-related condition (3 variants)
• Intellectual disability (2 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (2 variants)
• Abnormal brain morphology (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (1 variants)
• POMGNT1-Related Disorders (1 variants)
• See cases (1 variants)
• Congenital muscular alpha-dystroglycanopathy with brain and eye anomalies (1 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;Autosomal recessive limb-girdle muscular dystrophy type 2N;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (1 variants)
• - (1 variants)
• Congenital muscular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMT2 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			15	104	5	124
missense	1	7	326	3	2	339
nonsense	14	6	1			21
start loss						0
frameshift	12	18	2			32
inframe indel			5			5
splice donor/acceptor (+/-2bp)	7	21	1			29
splice region			26	29	2	57
non coding		1	74	110	60	245
Total	34	53	424	217	67

Highest pathogenic variant AF is 0.0000328

Variants in POMT2

This is a list of pathogenic ClinVar variants found in the POMT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-77274995-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275006-C-CT		Limb-Girdle Muscular Dystrophy, Recessive	Uncertain significance (Jun 14, 2016)
14-77275017-T-A		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275051-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2N	Benign (Jan 13, 2018)
14-77275176-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275211-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275216-A-G		Limb-Girdle Muscular Dystrophy, Recessive	Uncertain significance (Jun 14, 2016)
14-77275225-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2N	Conflicting classifications of pathogenicity (Jun 01, 2023)
14-77275283-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 13, 2018)
14-77275285-C-A		Autosomal recessive limb-girdle muscular dystrophy type 2N	Likely benign (Jan 12, 2018)
14-77275296-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 13, 2018)
14-77275299-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 13, 2018)
14-77275304-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275323-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 13, 2018)
14-77275402-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Benign (Jan 13, 2018)
14-77275409-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2N	Benign (Jan 13, 2018)
14-77275470-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275483-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Likely benign (Jan 12, 2018)
14-77275558-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 13, 2018)
14-77275571-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275602-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275620-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2N	Likely benign (Jan 12, 2018)
14-77275627-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Uncertain significance (Jan 12, 2018)
14-77275628-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Benign (Jan 12, 2018)
14-77275634-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2N	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMT2	protein_coding	protein_coding	ENST00000261534	21	45929

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.43e-12	0.994	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0763	412	416	0.989	0.0000236	4818
Missense in Polyphen		121	154.13	0.78504		1830
Synonymous	0.289	162	167	0.972	0.00000920	1523
Loss of Function	2.65	25	43.9	0.569	0.00000232	473

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000446	0.000445
Ashkenazi Jewish	0.00	0.00
East Asian	0.000436	0.000435
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000276	0.000273
Middle Eastern	0.000436	0.000435
South Asian	0.000394	0.000392
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient. {ECO:0000269|PubMed:14699049}.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A2 (MDDGA2) [MIM:613150]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:15894594, ECO:0000269|PubMed:16701995, ECO:0000269|PubMed:17878207, ECO:0000269|PubMed:19138766, ECO:0000269|PubMed:22958903}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy congenital with mental retardation B2 (MDDGB2) [MIM:613156]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with mental retardation and mild structural brain abnormalities. {ECO:0000269|PubMed:17634419, ECO:0000269|PubMed:19299310}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C2 (MDDGC2) [MIM:613158]: An autosomal recessive muscular dystrophy with onset after ambulation is achieved. MDDGC2 is characterized by increased serum creatine kinase and mild muscle weakness. Muscle biopsy shows dystrophic changes, inflammatory changes, and severely decreased alpha-dystroglycan. Cognition is normal. {ECO:0000269|PubMed:17878207, ECO:0000269|PubMed:17923109}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Other types of O-glycan biosynthesis - Homo sapiens (human);Mannose type O-glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.152
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.68

Haploinsufficiency Scores

• pHI: 0.341
• hipred: N
• hipred_score: 0.414
• ghis: 0.587

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.459

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pomt2
• Phenotype: cellular phenotype; growth/size/body region 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); 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); embryo phenotype

Zebrafish Information Network

• Gene name: pomt2
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: kinked

Gene ontology

• Biological process: protein O-linked mannosylation;ER-associated misfolded protein catabolic process;positive regulation of protein O-linked glycosylation
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: dolichyl-phosphate-mannose-protein mannosyltransferase activity;metal ion binding