myopia 26, X-linked, female-limited

Summary

myopia 26, X-linked, female-limited (MONDO:0049221) is a disease caused by ARR3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ARR3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 26, X-linked, female-limited
Mondo ID	MONDO:0049221
OMIM	301010
UMLS	C4538795
MedGen	1618364
Is cancer (heuristic)	no

Also known as: myopia 26, X-linked, female-limited · MYP26

Data availability: 11 ClinVar variants · 2 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 26, X-linked, female-limited

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 28, autosomal recessive, myopia 27

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

11 retrieved; paginated sample, class counts are floors:

5 pathogenic, 4 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1697230	NM_004312.3(ARR3):c.214C>T (p.Arg72Ter)	ARR3	Pathogenic	criteria provided, single submitter
3250960	NM_004312.3(ARR3):c.767+1G>A	ARR3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4071984	NM_004312.3(ARR3):c.905+2del	ARR3	Pathogenic	criteria provided, single submitter
478824	NM_004312.3(ARR3):c.893C>A (p.Ala298Asp)	ARR3	Pathogenic	no assertion criteria provided
478825	NM_004312.3(ARR3):c.298C>T (p.Arg100Ter)	ARR3	Pathogenic	no assertion criteria provided
478826	NM_004312.3(ARR3):c.239T>C (p.Leu80Pro)	ARR3	Pathogenic	no assertion criteria provided
2672269	NM_004312.3(ARR3):c.553C>T (p.Arg185Cys)	ARR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892987	NM_004312.3(ARR3):c.1076+1G>A	ARR3	Uncertain significance	criteria provided, single submitter
4530595	NM_004312.3(ARR3):c.965T>A (p.Val322Asp)	ARR3	Uncertain significance	criteria provided, single submitter
4533227	NM_004312.3(ARR3):c.609+5G>C	ARR3	Uncertain significance	criteria provided, single submitter
4533229	NM_004312.3(ARR3):c.843del (p.Lys281fs)	ARR3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
ARR3	Strong	X-linked	myopia 26, X-linked, female-limited	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARR3	HGNC:710	ENSG00000120500	P36575	Arrestin-C	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARR3	Arrestin-C	May play a role in an as yet undefined retina-specific signal transduction.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARR3	Other/Unknown	no		Arrestin, Arrestin-like_N, Arrestin-like_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARR3	160	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, sperm, male germ cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARR3	1,282

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARR3	P36575	87.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
G protein-coupled receptor internalization	1	1685.2×	0.002	ARR3
visual perception	1	79.5×	0.019	ARR3
signal transduction	1	16.1×	0.062	ARR3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ARR3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	ARR3

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)
ARR3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.