MYOC
myocilin
Basic information
Region (hg38): 1:171635417-171652688
Previous symbols: [ "GLC1A" ]
Links
Phenotypes
GenCC
Source:
- glaucoma 1, open angle, A (Definitive), mode of inheritance: AD
- glaucoma 1, open angle, A (Strong), mode of inheritance: AD
- congenital glaucoma (Supportive), mode of inheritance: AD
- juvenile open angle glaucoma (Supportive), mode of inheritance: AD
- glaucoma 1, open angle, A (Definitive), mode of inheritance: AD
- open-angle glaucoma (Definitive), mode of inheritance: AD
- juvenile open angle glaucoma (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Glaucoma 1, open angle, A | AD/AR/Digenic | Ophthalmologic; Pharmacogenomic | Early diagnosis and treatment may be effective to decrease morbidity and mortality related to vision loss; Agents that may contribute to glaucoma should be avoided | Ophthalmologic | 8513321; 9005853; 9535666; 10330365; 11535458; 11709019; 11774072; 15025728; 15108121; 15733270; 17562996; 17197538; 17499207 |
| Digenic inheritance (with CYP1B1) has been reported |
ClinVar
This is a list of variants' phenotypes submitted to
- Open-angle_glaucoma (114 variants)
- Glaucoma_of_childhood (93 variants)
- Glaucoma_1,_open_angle,_A (66 variants)
- Glaucoma_1,_open_angle,_E (56 variants)
- not_provided (53 variants)
- Glaucoma (38 variants)
- Inborn_genetic_diseases (26 variants)
- MYOC-related_disorder (14 variants)
- not_specified (9 variants)
- Primary_open_angle_glaucoma (2 variants)
- Constitutional_megaloblastic_anemia_with_severe_neurologic_disease (1 variants)
- RECLASSIFIED_-_MYOC_POLYMORPHISM (1 variants)
- GLAUCOMA_1,_OPEN_ANGLE,_A,_DIGENIC (1 variants)
- GLAUCOMA_3,_PRIMARY_CONGENITAL,_A,_DIGENIC (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYOC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000261.2. 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 | 30 | 18 | 54 | |||
| missense | 21 | 160 | 18 | 207 | ||
| nonsense | 13 | 16 | ||||
| start loss | 0 | |||||
| frameshift | 14 | 14 | ||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 9 | 21 | 218 | 37 | 7 |
Highest pathogenic variant AF is 0.00115863
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MYOC | protein_coding | protein_coding | ENST00000037502 | 3 | 17267 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 7.63e-12 | 0.135 | 125151 | 3 | 594 | 125748 | 0.00238 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.520 | 253 | 277 | 0.912 | 0.0000158 | 3280 |
| Missense in Polyphen | 64 | 91.106 | 0.70248 | 1113 | ||
| Synonymous | -0.0927 | 115 | 114 | 1.01 | 0.00000652 | 1013 |
| Loss of Function | 0.638 | 19 | 22.2 | 0.854 | 0.00000158 | 224 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00270 | 0.00270 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00973 | 0.00967 |
| Finnish | 0.00420 | 0.00421 |
| European (Non-Finnish) | 0.00203 | 0.00202 |
| Middle Eastern | 0.00973 | 0.00967 |
| South Asian | 0.00131 | 0.00127 |
| Other | 0.000815 | 0.000815 |
dbNSFP
Source:
- Function
- FUNCTION: Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling. Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling. Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling. Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex. Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork. {ECO:0000250|UniProtKB:O70624, ECO:0000269|PubMed:17516541, ECO:0000269|PubMed:17984096, ECO:0000269|PubMed:18855004, ECO:0000269|PubMed:19188438, ECO:0000269|PubMed:19959812, ECO:0000269|PubMed:21656515, ECO:0000269|PubMed:23629661, ECO:0000269|PubMed:23897819}.;
- Disease
- DISEASE: Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. {ECO:0000269|PubMed:10196380, ECO:0000269|PubMed:10330365, ECO:0000269|PubMed:10340788, ECO:0000269|PubMed:10644174, ECO:0000269|PubMed:10798654, ECO:0000269|PubMed:10819638, ECO:0000269|PubMed:10873982, ECO:0000269|PubMed:10916185, ECO:0000269|PubMed:10980537, ECO:0000269|PubMed:11004290, ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:12356829, ECO:0000269|PubMed:12362081, ECO:0000269|PubMed:12442283, ECO:0000269|PubMed:12860809, ECO:0000269|PubMed:12872267, ECO:0000269|PubMed:15025728, ECO:0000269|PubMed:15255110, ECO:0000269|PubMed:15534471, ECO:0000269|PubMed:15795224, ECO:0000269|PubMed:16401791, ECO:0000269|PubMed:17210859, ECO:0000269|PubMed:17499207, ECO:0000269|PubMed:25524706, ECO:0000269|PubMed:9005853, ECO:0000269|PubMed:9328473, ECO:0000269|PubMed:9345106, ECO:0000269|PubMed:9361308, ECO:0000269|PubMed:9490287, ECO:0000269|PubMed:9510647, ECO:0000269|PubMed:9521427, ECO:0000269|PubMed:9535666, ECO:0000269|PubMed:9697688, ECO:0000269|PubMed:9792882, ECO:0000269|PubMed:9863594}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:15733270}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. MYOC mutations may contribute to GLC3A via digenic inheritance with CYP1B1 and/or another locus associated with the disease (PubMed:15733270). {ECO:0000269|PubMed:15733270}.;
Recessive Scores
- pRec
- 0.410
Intolerance Scores
- loftool
- 0.209
- rvis_EVS
- -0.13
- rvis_percentile_EVS
- 43.91
Haploinsufficiency Scores
- pHI
- 0.492
- hipred
- N
- hipred_score
- 0.229
- ghis
- 0.495
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.594
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Myoc
- Phenotype
- vision/eye phenotype; normal phenotype;
Gene ontology
- Biological process
- osteoblast differentiation;negative regulation of cell-matrix adhesion;positive regulation of phosphatidylinositol 3-kinase signaling;skeletal muscle hypertrophy;myelination in peripheral nervous system;positive regulation of cell migration;neuron projection development;negative regulation of Rho protein signal transduction;non-canonical Wnt signaling pathway via JNK cascade;ERBB2-ERBB3 signaling pathway;regulation of MAPK cascade;clustering of voltage-gated sodium channels;positive regulation of stress fiber assembly;negative regulation of stress fiber assembly;positive regulation of focal adhesion assembly;positive regulation of protein kinase B signaling;positive regulation of mitochondrial depolarization;bone development;positive regulation of substrate adhesion-dependent cell spreading
- Cellular component
- extracellular space;mitochondrial outer membrane;mitochondrial inner membrane;mitochondrial intermembrane space;endoplasmic reticulum;rough endoplasmic reticulum;Golgi apparatus;cilium;cytoplasmic vesicle;node of Ranvier;collagen-containing extracellular matrix;extracellular exosome
- Molecular function
- fibronectin binding;frizzled binding;protein binding;receptor tyrosine kinase binding;myosin light chain binding;metal ion binding