Leber congenital amaurosis 19

disease

On this page

Also known as LCA19

Summary

Leber congenital amaurosis 19 (MONDO:0032794) is a disease caused by USP45 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: USP45 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 19
Mondo ID	MONDO:0032794
OMIM	618513
DOID	DOID:0081169
UMLS	C5193139
MedGen	1679297
GARD	0016359
Is cancer (heuristic)	no

Also known as: LCA19

Data availability: 14 ClinVar variants · 3 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 19

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

14 retrieved; paginated sample, class counts are floors:

6 benign, 3 uncertain significance, 3 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
638072	NM_001346022.3(USP45):c.935G>A (p.Arg312Gln)	USP45	Pathogenic	no assertion criteria provided
2443296	NM_001346022.3(USP45):c.1327C>T (p.Arg443Ter)	USP45	Likely pathogenic	criteria provided, single submitter
3901119	NM_001346022.3(USP45):c.931_932del (p.Lys311fs)	USP45	Likely pathogenic	no assertion criteria provided
4849450	NM_001346022.3(USP45):c.878_881del (p.Asp293fs)	USP45	Likely pathogenic	criteria provided, single submitter
3249131	NM_001346022.3(USP45):c.658G>T (p.Glu220Ter)	USP45	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2361978	NM_001346022.3(USP45):c.1709G>A (p.Gly570Glu)	USP45	Uncertain significance	criteria provided, multiple submitters, no conflicts
2438495	NM_001346022.3(USP45):c.377+5G>A	USP45	Uncertain significance	criteria provided, single submitter
638073	NM_001346022.3(USP45):c.1636A>T (p.Lys546Ter)	USP45	Uncertain significance	criteria provided, single submitter
1684198	NM_001346022.3(USP45):c.2333A>G (p.Asn778Ser)	USP45	Benign	criteria provided, single submitter
1684199	NM_001346022.3(USP45):c.1710A>G (p.Gly570=)	USP45	Benign	criteria provided, single submitter
1684200	NM_001346022.3(USP45):c.1562G>C (p.Arg521Thr)	USP45	Benign	criteria provided, single submitter
1684201	NM_001346022.3(USP45):c.1309-26_1309-22del	USP45	Benign	criteria provided, single submitter
1684202	NM_001346022.3(USP45):c.378-9C>T	USP45	Benign	criteria provided, single submitter
1684203	NM_001346022.3(USP45):c.199A>G (p.Lys67Glu)	USP45	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
USP45	Strong	Autosomal recessive	Leber congenital amaurosis 19	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
USP45	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
USP45	HGNC:20080	ENSG00000123552	Q70EL2	Ubiquitin carboxyl-terminal hydrolase 45	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USP45	Ubiquitin carboxyl-terminal hydrolase 45	Catalyzes the deubiquitination of SPDL1.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USP45	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD

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
calcaneal tendon	1
epithelial cell of pancreas	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USP45	225	ubiquitous	marker	calcaneal tendon, secondary oocyte, epithelial cell of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
USP45	951

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
USP45	Q70EL2	66.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Formation of Incision Complex in GG-NER	1	253.8×	0.004	USP45

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
global genome nucleotide-excision repair	1	8426.0×	8e-04	USP45
neural retina development	1	936.2×	0.004	USP45
photoreceptor cell maintenance	1	358.6×	0.007	USP45
protein deubiquitination	1	177.4×	0.010	USP45
DNA repair	1	63.8×	0.019	USP45
cell migration	1	61.5×	0.019	USP45
proteolysis	1	34.2×	0.029	USP45

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
USP45	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
USP45	3	Binding:3

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	1	USP45
E	Difficult family or no structure, no drug	0

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)
USP45	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: USP45