MYOC

Chr 1AD

myocilin

Also known as: GLC1A, GPOA, JOAG, JOAG1, TIGR

NCBI Gene: 4653 ENSG00000034971 UniProt: Q99972 OMIM: 601652

Myocilin is a secreted glycoprotein that regulates cell adhesion, cytoskeleton organization, and fluid outflow in the trabecular meshwork of the eye. Mutations cause autosomal dominant juvenile-onset primary open-angle glaucoma (Glaucoma 1A). The gene is not highly constrained against loss-of-function variants, consistent with its association with a specific tissue-related phenotype rather than systemic developmental abnormalities.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

MYOC encodes the protein myocilin, which is believed to have a role in cytoskeletal function. MYOC is expressed in many occular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glaucoma 1A, primary open angleMIM #137750

UniProtGlaucoma 1, open angle, A

UniProtGlaucoma 3, primary congenital, A

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · open-angle glaucoma · AD · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.25

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.000

Z-score 0.64

OE 0.85 (0.59–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.52Z-score

OE missense 0.91 (0.82–1.01)

253 obs / 277.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.85 (0.59–1.25)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 19 / 22.2Missense obs/exp: 253 / 277.4Syn Z: -0.09

Background carrier burden — how many people carry a rare variant somewhere in MYOC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

615 rare PASS variants

Rare truncating (LoF)

1 in 710

101 rare PASS variants

Rare synonymous (reference)

1 in 130

252 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MYOC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,100
South Asian	~43k	1 in 85	1 in 460
Remaining (unassigned)	~30k	1 in 59	1 in 280
European (Finnish)	~27k	1 in 320	1 in 1,000
Admixed American	~22k	1 in 90	1 in 590
African / African American	~21k	1 in 99	1 in 380
East Asian	~20k	1 in 78	1 in 2,200
Ashkenazi Jewish	~13k	1 in 530	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 97	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓