MYOC

myocilin

Basic information

Region (hg38): 1:171635416-171652688

Previous symbols: [ "GLC1A" ]

Links

ENSG00000034971 ∙ NCBI:4653 ∙ OMIM:601652 ∙ HGNC:7610 ∙ Uniprot:Q99972 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glaucoma 3A (Limited), mode of inheritance: AD
• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the MYOC gene.

• Glaucoma of childhood (104 variants)
• Open-angle glaucoma (98 variants)
• Glaucoma 1, open angle, A (73 variants)
• Glaucoma 1, open angle, E (63 variants)
• not provided (55 variants)
• Glaucoma (48 variants)
• Inborn genetic diseases (13 variants)
• not specified (11 variants)
• MYOC-Related Disorders (4 variants)
• Primary open angle glaucoma (2 variants)
• Glaucoma 1, open angle, a, digenic (1 variants)
• Glaucoma 1, open angle, a, autosomal recessive (1 variants)
• 6 conditions (1 variants)
• Glaucoma 3, primary congenital, a, digenic (1 variants)
• MYOC-related condition (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.

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			30	18	7	55
missense	7	20	147	18	2	194
nonsense	1		13	1		15
start loss						0
frameshift			14			14
inframe indel		2	2			4
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding			7	3	11	21
Total	8	22	214	40	20

Highest pathogenic variant AF is 0.000848

Variants in MYOC

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

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

Position	Type	Phenotype	Significance	ClinVar
1-171635499-G-A		Glaucoma 1, open angle, A • Glaucoma	Uncertain significance (Jan 13, 2018)
1-171635594-T-C		Glaucoma • Glaucoma 1, open angle, A	Uncertain significance (Jan 13, 2018)
1-171635652-C-T		Glaucoma 1, open angle, A • Glaucoma	Uncertain significance (Jan 13, 2018)
1-171635684-T-C		Glaucoma 1, open angle, A • Glaucoma	Uncertain significance (Jan 13, 2018)
1-171635737-G-A		Glaucoma 1, open angle, A • Glaucoma	Uncertain significance (Jan 12, 2018)
1-171635743-G-T		Glaucoma • Glaucoma 1, open angle, A	Uncertain significance (Jan 12, 2018)
1-171635852-C-G		Glaucoma 1, open angle, A • Glaucoma	Benign (Apr 27, 2017)
1-171635854-C-T		Glaucoma • Glaucoma 1, open angle, A	Uncertain significance (Jan 13, 2018)
1-171635925-T-C		Glaucoma of childhood	Uncertain significance (May 02, 2023)
1-171635936-A-G		Glaucoma of childhood	Uncertain significance (May 09, 2022)
1-171635941-T-C		Open-angle glaucoma • MYOC-related disorder	Likely benign (Jul 05, 2023)
1-171635944-A-C		Glaucoma of childhood	Uncertain significance (May 09, 2022)
1-171635945-T-A		Glaucoma of childhood	Likely pathogenic (May 09, 2022)
1-171635948-C-G		Open-angle glaucoma	Uncertain significance (Apr 03, 2023)
1-171635949-A-C			Uncertain significance (Jan 20, 2014)
1-171635954-T-G		Open-angle glaucoma	Uncertain significance (Feb 15, 2023)
1-171635957-C-T		Glaucoma 1, open angle, E	Uncertain significance (May 09, 2022)
1-171635973-C-CG		Open-angle glaucoma	Uncertain significance (May 31, 2023)
1-171635974-C-T		Open-angle glaucoma	Uncertain significance (May 31, 2023)
1-171635976-G-A		Open-angle glaucoma	Likely benign (May 02, 2023)
1-171635977-G-A		Open-angle glaucoma	Uncertain significance (Jul 05, 2023)
1-171635984-G-A		Glaucoma of childhood	Uncertain significance (Dec 14, 2022)
1-171635988-C-T		Glaucoma of childhood	Uncertain significance (Feb 15, 2023)
1-171635993-C-A		Open-angle glaucoma	Uncertain significance (Apr 03, 2023)
1-171635998-G-A		Glaucoma of childhood	Likely pathogenic (May 09, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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