Leber congenital amaurosis 12

Summary

Leber congenital amaurosis 12 (MONDO:0012525) is a disease caused by RD3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RD3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 229

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 12
Mondo ID	MONDO:0012525
MeSH	C565697
OMIM	610612
DOID	DOID:0110080
UMLS	C1857743
MedGen	347535
GARD	0010489
Is cancer (heuristic)	no

Also known as: amaurosis congenita of Leber, type 12 · LCA12 · Leber congenital amaurosis 12 · Leber congenital amaurosis caused by mutation in RD3 · Leber congenital amaurosis type 12 · RD3 Leber congenital amaurosis

Data availability: 229 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Leber congenital amaurosis › Leber congenital amaurosis 12

Related subtypes (20): retinal aplasia, Leber congenital amaurosis 1, Leber congenital amaurosis 2, Leber congenital amaurosis 3, Leber congenital amaurosis 4, Leber congenital amaurosis 5, Leber congenital amaurosis 9, Leber congenital amaurosis 10, Leber congenital amaurosis 13, Leber congenital amaurosis 14, Leber congenital amaurosis 6, Leber congenital amaurosis 7, Leber congenital amaurosis 8, Leber congenital amaurosis 11, Leber congenital amaurosis 15, Leber congenital amaurosis 16, Leber congenital amaurosis 17, Leber congenital amaurosis 19, Leber congenital amaurosis with early-onset deafness, Leber congenital amaurosis 18

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

229 retrieved; paginated sample, class counts are floors:

143 uncertain significance, 48 likely benign, 13 benign, 11 pathogenic, 9 conflicting classifications of pathogenicity, 2 likely pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13121	NM_001164688.2(RD3):c.296+1G>A	RD3	Pathogenic	no assertion criteria provided
1388540	NM_001164688.2(RD3):c.296+1G>T	RD3	Pathogenic	criteria provided, single submitter
1458859	NM_001164688.2(RD3):c.13_14del (p.Ser5fs)	RD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189791	NM_001164688.2(RD3):c.180C>A (p.Tyr60Ter)	RD3	Pathogenic	criteria provided, multiple submitters, no conflicts
189792	NM_001164688.2(RD3):c.112C>T (p.Arg38Ter)	RD3	Pathogenic	criteria provided, multiple submitters, no conflicts
189793	NM_001164688.2(RD3):c.137_138del (p.Glu46fs)	RD3	Pathogenic	no assertion criteria provided
189794	NM_001164688.2(RD3):c.136G>T (p.Glu46Ter)	RD3	Pathogenic	no assertion criteria provided
2003233	NM_001164688.2(RD3):c.38del (p.Pro13fs)	RD3	Pathogenic	criteria provided, single submitter
2106862	NM_001164688.2(RD3):c.238C>T (p.Gln80Ter)	RD3	Pathogenic	criteria provided, single submitter
2427618	NC_000001.10:g.(?211652378)(211654757_?)del	RD3	Pathogenic	criteria provided, single submitter
3663320	NM_001164688.2(RD3):c.80_102del (p.Glu27fs)	RD3	Pathogenic	criteria provided, single submitter
4077377	NM_001164688.2(RD3):c.296+641_*606del	RD3	Pathogenic	criteria provided, single submitter
3578445	NM_001164688.2(RD3):c.265del (p.His89fs)	RD3	Likely pathogenic	criteria provided, single submitter
4077376	NM_001164688.2(RD3):c.394G>T (p.Glu132Ter)	RD3	Likely pathogenic	criteria provided, single submitter
167572	NM_001164688.2(RD3):c.139C>T (p.Arg47Cys)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283908	NM_001164688.2(RD3):c.168C>T (p.Thr56=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283917	NM_001164688.2(RD3):c.498C>T (p.Ile166=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287750	NM_001164688.2(RD3):c.135G>A (p.Arg45=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295256	NM_001164688.2(RD3):c.468C>T (p.Arg156=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
733845	NM_001164688.2(RD3):c.102G>A (p.Thr34=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
767424	NM_001164688.2(RD3):c.494A>C (p.Asp165Ala)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772783	NM_001164688.2(RD3):c.519G>A (p.Val173=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874725	NM_001164688.2(RD3):c.150G>A (p.Ala50=)	RD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000912	NM_001164688.2(RD3):c.31G>A (p.Glu11Lys)	RD3	Uncertain significance	criteria provided, single submitter
1002125	NM_001164688.2(RD3):c.368A>T (p.Gln123Leu)	RD3	Uncertain significance	criteria provided, single submitter
1007256	NM_001164688.2(RD3):c.325C>T (p.Pro109Ser)	RD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1013705	NM_001164688.2(RD3):c.55A>T (p.Arg19Trp)	RD3	Uncertain significance	criteria provided, single submitter
1024198	NM_001164688.2(RD3):c.65C>A (p.Ala22Asp)	RD3	Uncertain significance	criteria provided, single submitter
1026526	NM_001164688.2(RD3):c.22C>T (p.Arg8Trp)	RD3	Uncertain significance	criteria provided, single submitter
1036152	NM_001164688.2(RD3):c.203G>A (p.Arg68Gln)	RD3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RD3	Definitive	Autosomal recessive	Leber congenital amaurosis 12	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RD3	Orphanet:65	Leber congenital amaurosis

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
RD3	HGNC:19689	ENSG00000198570	Q7Z3Z2	Protein RD3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RD3	Protein RD3	Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors.

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)
RD3	Other/Unknown	no		RD3

Expression context

Cohort genes with no expression data: 0.

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
buccal mucosa cell	1
primordial germ cell in gonad	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RD3	90	tissue_specific	yes	primordial germ cell in gonad, buccal mucosa cell, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RD3	718

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RD3	Q7Z3Z2	1

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
negative regulation of guanylate cyclase activity	1	16852.0×	2e-04	RD3
retina development in camera-type eye	1	255.3×	0.008	RD3
visual perception	1	79.5×	0.017	RD3
protein transport	1	43.9×	0.023	RD3

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
RD3	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	RD3

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)
RD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.