Leber congenital amaurosis 11

Summary

Leber congenital amaurosis 11 (MONDO:0013454) is a disease caused by IMPDH1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: IMPDH1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 86

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 11
Mondo ID	MONDO:0013454
MeSH	C564140
OMIM	613837
DOID	DOID:0110216
UMLS	C1840284
MedGen	326698
GARD	0010488
Is cancer (heuristic)	no

Also known as: amaurosis congenita of Leber, type 11 · IMPDH1 Leber congenital amaurosis · LCA11 · Leber congenital amaurosis 11 · Leber congenital amaurosis caused by mutation in IMPDH1 · Leber congenital amaurosis type 11

Data availability: 86 ClinVar variants · 2 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 11

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 12, 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 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

86 retrieved; paginated sample, class counts are floors:

45 uncertain significance, 27 conflicting classifications of pathogenicity, 5 benign/likely benign, 5 benign, 1 pathogenic, 1 likely pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14838	NM_000883.4(IMPDH1):c.849T>G (p.Asn283Lys)	IMPDH1	Pathogenic	no assertion criteria provided
937932	NM_000883.4(IMPDH1):c.968A>G (p.Lys323Arg)	IMPDH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374177	NM_000883.4(IMPDH1):c.928A>C (p.Thr310Pro)	IMPDH1	Likely pathogenic	criteria provided, single submitter
1147181	NM_000883.4(IMPDH1):c.218G>A (p.Gly73Asp)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14837	NM_000883.4(IMPDH1):c.568C>T (p.Arg190Trp)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193819	NM_000883.4(IMPDH1):c.1108G>A (p.Ala370Thr)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197169	NM_000883.4(IMPDH1):c.336C>T (p.Ala112=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2062530	NM_000883.4(IMPDH1):c.1490G>A (p.Arg497Gln)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358868	NM_000883.4(IMPDH1):c.*223C>G	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358872	NM_000883.4(IMPDH1):c.1653C>T (p.His551=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358874	NM_000883.4(IMPDH1):c.1350C>T (p.Gly450=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358875	NM_000883.4(IMPDH1):c.1338C>T (p.Ile446=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358877	NM_000883.4(IMPDH1):c.888C>T (p.Ile296=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358878	NM_000883.4(IMPDH1):c.769A>G (p.Thr257Ala)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
444730	NM_000883.4(IMPDH1):c.377T>C (p.Phe126Ser)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
636175	NM_000883.4(IMPDH1):c.1598A>G (p.Gln533Arg)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
707014	NM_000883.4(IMPDH1):c.1142A>G (p.His381Arg)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
711446	NM_000883.4(IMPDH1):c.1668C>T (p.Ile556=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
729916	NM_000883.4(IMPDH1):c.1662G>A (p.Gln554=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
767199	NM_000883.4(IMPDH1):c.189A>G (p.Ser63=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772300	NM_000883.4(IMPDH1):c.930C>T (p.Thr310=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
813046	NM_000883.4(IMPDH1):c.71G>C (p.Arg24Pro)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909847	NM_000883.4(IMPDH1):c.*196C>T	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909951	NM_000883.4(IMPDH1):c.675T>C (p.Ser225=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910797	NM_000883.4(IMPDH1):c.1280C>T (p.Pro427Leu)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910798	NM_000883.4(IMPDH1):c.1226G>A (p.Gly409Asp)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910850	NM_000883.4(IMPDH1):c.561C>T (p.Asn187=)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
912068	NM_000883.4(IMPDH1):c.255-10C>T	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931488	NM_000883.4(IMPDH1):c.942G>T (p.Lys314Asn)	IMPDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358880	NM_000883.4(IMPDH1):c.146+9C>T	LOC129999258	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
IMPDH1	Definitive	Autosomal dominant	Leber congenital amaurosis 11	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IMPDH1	Orphanet:65	Leber congenital amaurosis
IMPDH1	Orphanet:791	Retinitis pigmentosa

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
IMPDH1	HGNC:6052	ENSG00000106348	P20839	Inosine-5’-monophosphate dehydrogenase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IMPDH1	Inosine-5’-monophosphate dehydrogenase 1	Catalyzes the conversion of inosine 5’-phosphate (IMP) to xanthosine 5’-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IMPDH1	Enzyme (other)	yes	1.1.1.205	CBS_dom, IMP_DH_GMPRt, IMP_DH

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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IMPDH1	249	ubiquitous	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IMPDH1	3,227

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IMPDH1	P20839	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nucleotide biosynthesis	1	5710.0×	0.002	IMPDH1
Purine ribonucleoside monophosphate biosynthesis	1	1038.2×	0.007	IMPDH1
Azathioprine ADME	1	496.5×	0.009	IMPDH1
Metabolism of nucleotides	1	300.5×	0.012	IMPDH1
Drug ADME	1	228.4×	0.012	IMPDH1
Potential therapeutics for SARS	1	114.2×	0.020	IMPDH1
SARS-CoV Infections	1	55.4×	0.036	IMPDH1
Viral Infection Pathways	1	30.8×	0.055	IMPDH1
Innate Immune System	1	25.5×	0.055	IMPDH1
Infectious disease	1	24.8×	0.055	IMPDH1
Neutrophil degranulation	1	23.1×	0.055	IMPDH1
Disease	1	13.1×	0.083	IMPDH1
Immune System	1	13.0×	0.083	IMPDH1
Metabolism	1	11.6×	0.086	IMPDH1

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
lymphocyte proliferation	1	2407.4×	6e-04	IMPDH1
‘de novo’ XMP biosynthetic process	1	2106.5×	6e-04	IMPDH1
GMP biosynthetic process	1	1872.4×	6e-04	IMPDH1
GTP biosynthetic process	1	1685.2×	6e-04	IMPDH1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
IMPDH1	MYCOPHENOLIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IMPDH1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MYCOPHENOLIC ACID	4	IMPDH1
MERIMEPODIB	2	IMPDH1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
IMPDH1	46	Binding:40, Functional:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
IMPDH1	1.1.1.205	IMP dehydrogenase

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

2 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)
MYCOPHENOLIC ACID	4	IMPDH1
MERIMEPODIB	2	IMPDH1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	IMPDH1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.