GeneBe

POMT2

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

Basic information

Region (hg38): 14:77274956-77320883

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
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 2ARCardiovascularConditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical managementCardiovascular; Musculoskeletal; Neurologic; Ophthalmologic15894594; 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 (954 variants)
  • Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2N (940 variants)
  • Muscular_dystrophy-dystroglycanopathy_(congenital_with_intellectual_disability),_type_B2 (934 variants)
  • not_provided (315 variants)
  • Inborn_genetic_diseases (89 variants)
  • not_specified (85 variants)
  • POMT2-related_disorder (18 variants)
  • Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A1 (16 variants)
  • Autosomal_recessive_limb-girdle_muscular_dystrophy (8 variants)
  • Muscular_dystrophy (3 variants)
  • Intellectual_disability (2 variants)
  • Myopathy_caused_by_variation_in_POMT2 (2 variants)
  • POMGNT1-related_disorder (1 variants)
  • Abnormal_brain_morphology (1 variants)
  • Elevated_circulating_creatine_kinase_concentration (1 variants)
  • See_cases (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 POMT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013382.7. 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.

EffectPLPVUSLBBSum
synonymous
7
clinvar
252
clinvar
2
clinvar
 261
missense
5
clinvar
27
clinvar
380
clinvar
18
clinvar
1
clinvar
 431
nonsense
23
clinvar
13
clinvar
 36
start loss
0
frameshift
30
clinvar
31
clinvar
2
clinvar
 63
splice donor/acceptor (+/-2bp)
9
clinvar
28
clinvar
1
clinvar
 38
Total 67 99 390 270 3

Highest pathogenic variant AF is 0.0000942008

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
POMT2protein_codingprotein_codingENST00000261534 2145929
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
9.43e-120.9941256800681257480.000270
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.07634124160.9890.00002364818
Missense in Polyphen121154.130.785041830
Synonymous0.2891621670.9720.000009201523
Loss of Function2.652543.90.5690.00000232473

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004460.000445
Ashkenazi Jewish0.000.00
East Asian0.0004360.000435
Finnish0.0001390.000139
European (Non-Finnish)0.0002760.000273
Middle Eastern0.0004360.000435
South Asian0.0003940.000392
Other0.0003260.000326

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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