Myopia 28, autosomal recessive

Summary

Myopia 28, autosomal recessive (MONDO:0030697) is a disease caused by LOXL3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: LOXL3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 28, autosomal recessive
Mondo ID	MONDO:0030697
OMIM	619781
UMLS	C5676935
MedGen	1806812
Is cancer (heuristic)	no

Also known as: myopia 28, autosomal recessive · MYP28

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › myopia › myopia 28, autosomal recessive

Related subtypes (29): degenerative myopia, myopia 2, autosomal dominant, myopia 18, autosomal recessive, myopia 13, X-linked, myopia 1, X-linked, myopia 3, autosomal dominant, myopia 17, autosomal dominant, myopia 5, autosomal dominant, myopia 6, myopia 7, myopia 8, myopia 9, myopia 10, myopia 11, autosomal dominant, myopia 12, autosomal dominant, myopia 14, myopia 16, autosomal dominant, myopia 15, autosomal dominant, schizophrenia 16, myopia 19, autosomal dominant, myopia 20, autosomal dominant, myopia 21, autosomal dominant, myopia, high, with cataract and vitreoretinal degeneration, myopia 22, autosomal dominant, myopia 23, autosomal recessive, myopia 24, autosomal dominant, myopia 25, autosomal dominant, myopia 27, myopia 26, X-linked, female-limited

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1343102	NM_032603.5(LOXL3):c.594del (p.Gln199fs)	DOK1	Pathogenic	no assertion criteria provided
1810228	NM_032603.5(LOXL3):c.449delinsAA (p.Pro150fs)	LOXL3	Pathogenic	criteria provided, single submitter
3897710	NM_032603.5(LOXL3):c.313+1G>T	LOXL3	Likely pathogenic	criteria provided, single submitter
1343103	NM_032603.5(LOXL3):c.1036C>T (p.Arg346Trp)	LOXL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1433365	NM_032603.5(LOXL3):c.754del (p.Glu252fs)	LOXL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343101	NM_032603.5(LOXL3):c.39dup (p.Leu14fs)	DOK1	Uncertain significance	criteria provided, single submitter
1343104	NM_032603.5(LOXL3):c.824dup (p.Ala277fs)	LOXL3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1516700	NM_032603.5(LOXL3):c.5G>A (p.Arg2Gln)	LOXL3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LOXL3	Strong	Autosomal recessive	myopia 28, autosomal recessive	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LOXL3	Orphanet:250984	Autosomal recessive Stickler syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LOXL3	HGNC:13869	ENSG00000115318	P58215	Lysyl oxidase homolog 3	gencc,clinvar
DOK1	HGNC:2990	ENSG00000115325	Q99704	Docking protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LOXL3	Lysyl oxidase homolog 3	Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins.
DOK1	Docking protein 1	DOK proteins are enzymatically inert adaptor or scaffolding proteins.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	8.6×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LOXL3	Enzyme (other)	yes	1.4.3.13	SRCR, Lysyl_oxidase, Lysyl_oxidase_CS
DOK1	Scaffold/PPI	no		PH_domain, IRS_PTB, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tendon of biceps brachii	2
cartilage tissue	1
tibia	1
monocyte	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LOXL3	198	ubiquitous	marker	tibia, cartilage tissue, tendon of biceps brachii
DOK1	269	ubiquitous	marker	tendon of biceps brachii, pancreatic ductal cell, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LOXL3	1,130
DOK1	610

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DOK1	Q99704	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LOXL3	P58215	84.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1	1	634.4×	0.010	DOK1
Crosslinking of collagen fibrils	1	285.5×	0.010	LOXL3
Collagen formation	1	228.4×	0.010	LOXL3
Elastic fibre formation	1	167.9×	0.010	LOXL3
RET signaling	1	129.8×	0.011	DOK1
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.012	LOXL3
Extracellular matrix organization	1	31.6×	0.031	LOXL3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibronectin fibril organization	1	4213.0×	0.002	LOXL3
peptidyl-lysine oxidation	1	2808.7×	0.002	LOXL3
macrophage colony-stimulating factor signaling pathway	1	2808.7×	0.002	DOK1
negative regulation of T-helper 17 cell lineage commitment	1	1203.7×	0.004	LOXL3
positive regulation of integrin-mediated signaling pathway	1	648.1×	0.005	LOXL3
somite development	1	561.7×	0.005	LOXL3
spinal cord development	1	255.3×	0.010	LOXL3
epithelial to mesenchymal transition	1	156.0×	0.014	LOXL3
roof of mouth development	1	123.9×	0.014	LOXL3
collagen fibril organization	1	112.3×	0.014	LOXL3
Ras protein signal transduction	1	102.8×	0.014	DOK1
lung development	1	99.1×	0.014	LOXL3
cell surface receptor protein tyrosine kinase signaling pathway	1	86.9×	0.015	DOK1
cell surface receptor signaling pathway	1	32.0×	0.038	DOK1
inflammatory response	1	18.9×	0.059	LOXL3
negative regulation of DNA-templated transcription	1	15.8×	0.066	LOXL3
signal transduction	1	8.0×	0.121	DOK1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
LOXL3	PYRITHIONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LOXL3	3	4
DOK1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRITHIONE	4	LOXL3
DISULFIRAM	4	LOXL3
THIRAM	2	LOXL3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LOXL3	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LOXL3	1.4.3.13	protein-lysine 6-oxidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

3 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PYRITHIONE	4	LOXL3
DISULFIRAM	4	LOXL3
THIRAM	2	LOXL3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	LOXL3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DOK1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DOK1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.