POMT1

protein O-mannosyltransferase 1, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases

Basic information

Region (hg38): 9:131502788-131523806

Links

ENSG00000130714 ∙ NCBI:10585 ∙ OMIM:607423 ∙ HGNC:9202 ∙ Uniprot:Q9Y6A1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (Strong), 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 2K (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
• congenital muscular dystrophy without intellectual disability (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (Strong), mode of inheritance: AR
• myopathy caused by variation in POMT1 (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, 1; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1	AR	Cardiovascular	Conditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical management	Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	2494887; 11053679; 11320179; 12369018; 14678799; 15037715; 15792865; 15637732; 16717220; 16575835; 17878207; 19299310; 20065251; 22727687

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POMT1 gene.

• not provided (363 variants)
• Walker-Warburg congenital muscular dystrophy;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Autosomal recessive limb-girdle muscular dystrophy type 2K (194 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2K;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy (117 variants)
• not specified (116 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (107 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2K (106 variants)
• Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (79 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Autosomal recessive limb-girdle muscular dystrophy type 2K;Walker-Warburg congenital muscular dystrophy (76 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2K;Walker-Warburg congenital muscular dystrophy;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (73 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K (49 variants)
• Inborn genetic diseases (36 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (31 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2K;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (11 variants)
• Autosomal recessive limb-girdle muscular dystrophy (9 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Autosomal recessive limb-girdle muscular dystrophy type 2K (6 variants)
• Limb-Girdle Muscular Dystrophy, Recessive (5 variants)
• POMT1-related condition (5 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Autosomal recessive limb-girdle muscular dystrophy type 2K (3 variants)
• Myopathy caused by variation in POMT1 (2 variants)
• Dysgenesis of the cerebellar vermis (2 variants)
• Walker-Warburg congenital muscular dystrophy (2 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Autosomal recessive limb-girdle muscular dystrophy type 2K;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (2 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Autosomal recessive limb-girdle muscular dystrophy type 2K;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (2 variants)
• Congenital muscular dystrophy (2 variants)
• POMT1-Related Disorders (2 variants)
• Pyridoxine-dependent epilepsy (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2K;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1 variants)
• Severe global developmental delay;Seizure (1 variants)
• Gait disturbance;Cerebellar ataxia;Poor speech;Hearing impairment;Sensory neuropathy (1 variants)
• Abnormality of the nervous system (1 variants)
• Intellectual disability (1 variants)
• Abnormality of the musculature (1 variants)
• Limb-girdle muscular dystrophy due to POMK deficiency (1 variants)
• Ventriculomegaly;Abnormal brainstem morphology (1 variants)
• Muscular dystrophy-dystroglycanopathy, type C (1 variants)
• Neurodevelopmental abnormality (1 variants)
• - (1 variants)
• Abnormal brainstem morphology;Ventriculomegaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMT1 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			13	94	3	110
missense	6	10	306	8	2	332
nonsense	19	15	1	1		36
start loss						0
frameshift	27	29				56
inframe indel		2	8			10
splice donor/acceptor (+/-2bp)	4	15				19
splice region		2	26	18	1	47
non coding		5	26	108	59	198
Total	56	76	354	211	64

Highest pathogenic variant AF is 0.000204

Variants in POMT1

This is a list of pathogenic ClinVar variants found in the POMT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-131502908-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 13, 2018)
9-131502909-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 13, 2018)
9-131502936-G-C		Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 13, 2018)
9-131503021-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 12, 2018)
9-131503067-A-G			Likely benign (Apr 19, 2018)
9-131503089-C-G		not specified	Likely benign (Jun 12, 2017)
9-131503298-C-CG		not specified	Likely benign (Oct 03, 2016)
9-131504173-C-T		not specified	Likely benign (Apr 26, 2017)
9-131504189-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 12, 2018)
9-131504191-C-T		POMT1-related disorder	Likely benign (Jul 03, 2019)
9-131504197-C-T		Limb-Girdle Muscular Dystrophy, Recessive	Uncertain significance (Jun 14, 2016)
9-131504199-T-C		not specified	Likely benign (Jul 20, 2017)
9-131504213-T-G		not specified • Autosomal recessive limb-girdle muscular dystrophy type 2K	Benign/Likely benign (Apr 27, 2017)
9-131504225-G-T		Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K	Pathogenic (Feb 14, 2023)
9-131504226-G-A		Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Aug 23, 2022)
9-131504241-C-T		Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 28, 2022)
9-131504244-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2K	Uncertain significance (Jan 12, 2018)
9-131504248-G-A		Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K	Conflicting classifications of pathogenicity (Jan 20, 2024)
9-131504251-G-T			Likely benign (Dec 01, 2023)
9-131504254-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2K • Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K	Conflicting classifications of pathogenicity (Jan 18, 2024)
9-131504254-G-T		Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Walker-Warburg congenital muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2K	Likely benign (Oct 26, 2023)
9-131504260-C-T		not specified • Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1;Autosomal recessive limb-girdle muscular dystrophy type 2K;Walker-Warburg congenital muscular dystrophy • POMT1-related disorder	Conflicting classifications of pathogenicity (Jan 20, 2024)
9-131504265-A-G			Uncertain significance (Sep 27, 2021)
9-131504270-A-C		Autosomal recessive limb-girdle muscular dystrophy type 2K;Walker-Warburg congenital muscular dystrophy;Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 • Inborn genetic diseases	Uncertain significance (Jun 23, 2022)
9-131504275-T-C		not specified	Conflicting classifications of pathogenicity (Nov 11, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMT1	protein_coding	protein_coding	ENST00000372228	19	20905

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.23e-17	0.687	101778	1602	22368	125748	0.100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.618	385	421	0.915	0.0000274	4830
Missense in Polyphen		150	176.3	0.85084		2117
Synonymous	-0.945	198	182	1.09	0.0000135	1486
Loss of Function	1.92	33	47.3	0.698	0.00000279	468

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.171	0.171
Ashkenazi Jewish	0.116	0.115
East Asian	0.000709	0.000707
Finnish	0.154	0.155
European (Non-Finnish)	0.132	0.131
Middle Eastern	0.000709	0.000707
South Asian	0.0499	0.0494
Other	0.106	0.105

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:12369018, ECO:0000269|PubMed:14699049}.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A1 (MDDGA1) [MIM:236670]: 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:12369018, ECO:0000269|PubMed:15037715, ECO:0000269|PubMed:15637732, ECO:0000269|PubMed:16575835}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C1 (MDDGC1) [MIM:609308]: An autosomal recessive degenerative myopathy associated with mild mental retardation without any obvious structural brain abnormality. An abnormal alpha- dystroglycan pattern in observed in the muscle. {ECO:0000269|PubMed:15792865}. 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: 0.238

Intolerance Scores

• loftool: 0.0172
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.26

Haploinsufficiency Scores

• pHI: 0.154
• hipred: N
• hipred_score: 0.426
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.473

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pomt1
• 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; 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); hematopoietic 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); embryo phenotype; immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: pomt1
• Affected structure: somite border
• Phenotype tag: abnormal
• Phenotype quality: curvature

Gene ontology

• Biological process: carbohydrate metabolic process;protein O-linked glycosylation;multicellular organism development;extracellular matrix organization;protein O-linked mannosylation;positive regulation of protein O-linked glycosylation
• Cellular component: acrosomal vesicle;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;sarcoplasmic reticulum
• Molecular function: mannosyltransferase activity;dolichyl-phosphate-mannose-protein mannosyltransferase activity;metal ion binding