Leber congenital amaurosis 16

Summary

Leber congenital amaurosis 16 (MONDO:0013613) is a disease caused by KCNJ13 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: KCNJ13 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 60

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 16
Mondo ID	MONDO:0013613
OMIM	614186
DOID	DOID:0110118
UMLS	C3280062
MedGen	481692
GARD	0010885
Is cancer (heuristic)	no

Also known as: KCNJ13 Leber congenital amaurosis · LCA16 · Leber congenital amaurosis 16 · Leber congenital amaurosis caused by mutation in KCNJ13 · Leber congenital amaurosis type 16

Data availability: 60 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 16

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 11, Leber congenital amaurosis 15, 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

60 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 6 pathogenic, 4 conflicting classifications of pathogenicity, 3 benign, 2 likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
191155	NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr)	GIGYF2	Pathogenic	criteria provided, single submitter
216947	NM_002242.4(KCNJ13):c.458C>T (p.Thr153Ile)	GIGYF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30331	NM_002242.4(KCNJ13):c.496C>T (p.Arg166Ter)	GIGYF2	Pathogenic	no assertion criteria provided
978432	NM_002242.4(KCNJ13):c.494del (p.Asn165fs)	GIGYF2	Pathogenic	no assertion criteria provided
224857	NM_002242.4(KCNJ13):c.158G>A (p.Trp53Ter)	KCNJ13	Pathogenic	no assertion criteria provided
30332	NM_002242.4(KCNJ13):c.722T>C (p.Leu241Pro)	KCNJ13	Pathogenic	no assertion criteria provided
978433	NM_002242.4(KCNJ13):c.655C>T (p.Gln219Ter)	KCNJ13	Pathogenic	no assertion criteria provided
916717	NM_002242.4(KCNJ13):c.431T>C (p.Leu144Pro)	KCNJ13	Likely pathogenic	criteria provided, single submitter
978434	NM_002242.4(KCNJ13):c.314G>T (p.Ser105Ile)	KCNJ13	Likely pathogenic	no assertion criteria provided
335038	NM_002242.4(KCNJ13):c.*1201C>T	GIGYF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
899320	NM_002242.4(KCNJ13):c.870G>A (p.Pro290=)	GIGYF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335057	NM_002242.4(KCNJ13):c.474G>A (p.Ala158=)	KCNJ13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
895230	NM_002242.4(KCNJ13):c.141C>T (p.Ile47=)	KCNJ13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335030	NM_002242.4(KCNJ13):c.*1881T>A	GIGYF2	Uncertain significance	criteria provided, single submitter
335031	NM_002242.4(KCNJ13):c.*1867T>C	GIGYF2	Uncertain significance	criteria provided, single submitter
335036	NM_002242.4(KCNJ13):c.*1500G>A	GIGYF2	Uncertain significance	criteria provided, single submitter
335040	NM_002242.4(KCNJ13):c.*957A>G	GIGYF2	Uncertain significance	criteria provided, single submitter
335051	NM_002242.4(KCNJ13):c.*102T>G	GIGYF2	Uncertain significance	criteria provided, single submitter
335055	NM_002242.4(KCNJ13):c.548G>A (p.Gly183Asp)	GIGYF2	Uncertain significance	criteria provided, single submitter
4279738	NM_002242.4(KCNJ13):c.155G>A (p.Arg52His)	GIGYF2	Uncertain significance	criteria provided, single submitter
895166	NM_002242.4(KCNJ13):c.*1635T>C	GIGYF2	Uncertain significance	criteria provided, single submitter
895167	NM_002242.4(KCNJ13):c.*1553T>G	GIGYF2	Uncertain significance	criteria provided, single submitter
895231	NM_002242.4(KCNJ13):c.125G>C (p.Arg42Pro)	GIGYF2	Uncertain significance	criteria provided, multiple submitters, no conflicts
896585	NM_002242.4(KCNJ13):c.*856A>G	GIGYF2	Uncertain significance	criteria provided, single submitter
896586	NM_002242.4(KCNJ13):c.*784T>C	GIGYF2	Uncertain significance	criteria provided, single submitter
896587	NM_002242.4(KCNJ13):c.*620G>A	GIGYF2	Uncertain significance	criteria provided, single submitter
898214	NM_002242.4(KCNJ13):c.*326A>G	GIGYF2	Uncertain significance	criteria provided, single submitter
899261	NM_002242.4(KCNJ13):c.*2007T>G	GIGYF2	Uncertain significance	criteria provided, single submitter
335029	NM_002242.4(KCNJ13):c.*2324C>T	KCNJ13	Uncertain significance	criteria provided, multiple submitters, no conflicts
335033	NM_002242.4(KCNJ13):c.*1804G>A	KCNJ13	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
KCNJ13	Definitive	Autosomal recessive	Leber congenital amaurosis 16	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNJ13	Orphanet:65	Leber congenital amaurosis
KCNJ13	Orphanet:91496	Snowflake vitreoretinal degeneration
GIGYF2	Orphanet:411602	Hereditary late-onset Parkinson disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNJ13	HGNC:6259	ENSG00000115474	O60928	Inward rectifier potassium channel 13	gencc,clinvar
GIGYF2	HGNC:11960	ENSG00000204120	Q6Y7W6	GRB10-interacting GYF protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNJ13	Inward rectifier potassium channel 13	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
GIGYF2	GRB10-interacting GYF protein 2	Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNJ13	Ion channel	yes		KCNJ13, K_chnl_inward-rec_Kir_cyto, Ig_E-set
GIGYF2	Other/Unknown	no		GYF, GYF-like_dom_sf, GRB10-interact_GYF

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
choroid plexus epithelium	1
pigmented layer of retina	1
retina	1
calcaneal tendon	1
colonic epithelium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNJ13	166	broad	marker	choroid plexus epithelium, pigmented layer of retina, retina
GIGYF2	291	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GIGYF2	2,914
KCNJ13	924

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNJ13	O60928	5
GIGYF2	Q6Y7W6	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
post-transcriptional gene silencing	1	2106.5×	0.007	GIGYF2
musculoskeletal movement	1	1404.3×	0.007	GIGYF2
mitotic G1 DNA damage checkpoint signaling	1	526.6×	0.007	GIGYF2
spinal cord motor neuron differentiation	1	468.1×	0.007	GIGYF2
negative regulation of translational initiation	1	443.5×	0.007	GIGYF2
negative regulation of type I interferon-mediated signaling pathway	1	383.0×	0.007	GIGYF2
regulation of monoatomic ion transmembrane transport	1	366.4×	0.007	KCNJ13
mRNA destabilization	1	337.0×	0.007	GIGYF2
feeding behavior	1	271.8×	0.008	GIGYF2
insulin-like growth factor receptor signaling pathway	1	247.8×	0.008	GIGYF2
rescue of stalled cytosolic ribosome	1	240.7×	0.008	GIGYF2
homeostasis of number of cells within a tissue	1	221.7×	0.008	GIGYF2
potassium ion import across plasma membrane	1	183.2×	0.008	KCNJ13
neuromuscular process controlling balance	1	165.2×	0.009	GIGYF2
adult locomotory behavior	1	150.5×	0.009	GIGYF2
regulation of membrane potential	1	115.4×	0.011	KCNJ13
post-embryonic development	1	102.8×	0.011	GIGYF2
negative regulation of translation	1	98.0×	0.011	GIGYF2
potassium ion transport	1	95.8×	0.011	KCNJ13
multicellular organism growth	1	68.5×	0.015	GIGYF2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
KCNJ13	0	0
GIGYF2	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
KCNJ13	9	Binding:9
GIGYF2	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	KCNJ13
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GIGYF2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KCNJ13	9	—
GIGYF2	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.