Myopia 23, autosomal recessive

Summary

Myopia 23, autosomal recessive (MONDO:0014183) is a disease caused by LRPAP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: LRPAP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 23, autosomal recessive
Mondo ID	MONDO:0014183
OMIM	615431
UMLS	C3809482
MedGen	815812
GARD	0018198
Is cancer (heuristic)	no

Also known as: myopia 23, autosomal recessive · MYP23

Data availability: 5 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 23, 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 24, autosomal dominant, myopia 25, autosomal dominant, myopia 28, autosomal recessive, 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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
190230	NM_002337.4(LRPAP1):c.199del (p.Gln67fs)	LOC129992120	Pathogenic	no assertion criteria provided
1526247	NM_002337.4(LRPAP1):c.705_708del (p.Asp236fs)	LRPAP1	Pathogenic	criteria provided, single submitter
65460	NM_002337.4(LRPAP1):c.605del (p.Asn202fs)	LRPAP1	Pathogenic	criteria provided, single submitter
65461	NM_002337.4(LRPAP1):c.863_864del (p.Ile288fs)	LOC126806953	Likely pathogenic	criteria provided, single submitter
4845813	NM_002337.4(LRPAP1):c.145G>T (p.Glu49Ter)	LOC129992120	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
LRPAP1	Definitive	Autosomal recessive	myopia 23, autosomal recessive	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRPAP1	Orphanet:98619	Rare isolated myopia

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
LRPAP1	HGNC:6701	ENSG00000163956	P30533	Alpha-2-macroglobulin receptor-associated protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRPAP1	Alpha-2-macroglobulin receptor-associated protein	Molecular chaperone for LDL receptor-related proteins that may regulate their ligand binding activity along the secretory pathway.

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)
LRPAP1	Other/Unknown	no		MG_RAP_rcpt_1, Alpha_2_MRAP_C, RAP_sf

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
right atrium auricular region	1
right coronary artery	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRPAP1	302	ubiquitous	marker	stromal cell of endometrium, right atrium auricular region, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRPAP1	1,607

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRPAP1	P30533	10

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
regulation of receptor-mediated endocytosis	1	16852.0×	5e-04	LRPAP1
extracellular negative regulation of signal transduction	1	8426.0×	5e-04	LRPAP1
negative regulation of very-low-density lipoprotein particle clearance	1	4213.0×	6e-04	LRPAP1
amyloid-beta clearance by transcytosis	1	2407.4×	8e-04	LRPAP1
positive regulation of amyloid-beta clearance	1	2106.5×	8e-04	LRPAP1
negative regulation of amyloid-beta clearance	1	1685.2×	8e-04	LRPAP1
negative regulation of receptor internalization	1	1203.7×	9e-04	LRPAP1
signal transduction	1	16.1×	0.062	LRPAP1

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
LRPAP1	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	LRPAP1

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)
LRPAP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.