Leber congenital amaurosis 15

Summary

Leber congenital amaurosis 15 (MONDO:0013457) is a disease caused by TULP1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TULP1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 101

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 15
Mondo ID	MONDO:0013457
OMIM	613843
DOID	DOID:0110189
UMLS	C3151206
MedGen	462556
GARD	0010884
Is cancer (heuristic)	no

Also known as: LCA15 · Leber congenital amaurosis 15 · Leber congenital amaurosis caused by mutation in TULP1 · Leber congenital amaurosis type 15 · TULP1 Leber congenital amaurosis

Data availability: 101 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 15

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 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

101 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 21 conflicting classifications of pathogenicity, 17 pathogenic, 16 pathogenic/likely pathogenic, 10 likely pathogenic, 7 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028595	NM_003322.6(TULP1):c.1255del (p.Arg419fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065758	NM_003322.6(TULP1):c.932G>A (p.Arg311Gln)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065768	NM_003322.6(TULP1):c.187G>T (p.Gly63Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1069193	NM_003322.6(TULP1):c.1255C>T (p.Arg419Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1675201	NM_003322.6(TULP1):c.790C>T (p.Gln264Ter)	TULP1	Pathogenic	criteria provided, single submitter
30260	NM_003322.6(TULP1):c.1204G>T (p.Glu402Ter)	TULP1	Pathogenic	no assertion criteria provided
30261	NM_003322.6(TULP1):c.1198C>T (p.Arg400Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30262	NM_003322.6(TULP1):c.1102G>T (p.Gly368Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30263	NM_003322.6(TULP1):c.1582_1587dup (p.Ala529_Ile530insPheAla)	TULP1	Pathogenic	no assertion criteria provided
3382016	NM_003322.6(TULP1):c.310del (p.Glu104fs)	TULP1	Pathogenic	criteria provided, single submitter
450005	NM_003322.6(TULP1):c.1024C>T (p.Arg342Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
7364	NM_003322.6(TULP1):c.1511_1521del (p.Leu504fs)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
802208	NM_003322.6(TULP1):c.1388del (p.Asn463fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802210	NM_003322.6(TULP1):c.931C>T (p.Arg311Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812440	NM_003322.6(TULP1):c.1047T>G (p.Asn349Lys)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
828151	NM_003322.6(TULP1):c.901C>T (p.Gln301Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
829968	NM_003322.6(TULP1):c.794del (p.Lys265fs)	TULP1	Pathogenic	no assertion criteria provided
852847	NM_003322.6(TULP1):c.1199G>A (p.Arg400Gln)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
865921	NM_003322.6(TULP1):c.821del (p.Lys274fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866967	NM_003322.6(TULP1):c.1318C>T (p.Arg440Ter)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
867084	NM_003322.6(TULP1):c.100C>T (p.Arg34Ter)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
872549	NM_003322.6(TULP1):c.629C>G (p.Ser210Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
931832	NM_003322.6(TULP1):c.1112+2T>G	TULP1	Pathogenic	criteria provided, single submitter
971453	NM_003322.6(TULP1):c.238C>T (p.Gln80Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
977975	NM_003322.6(TULP1):c.148del (p.Glu50fs)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
977976	NM_003322.6(TULP1):c.1081del (p.Arg361fs)	TULP1	Pathogenic	no assertion criteria provided
977980	NM_003322.6(TULP1):c.1445G>A (p.Arg482Gln)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
987369	NM_003322.6(TULP1):c.568G>T (p.Glu190Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
99663	NM_003322.6(TULP1):c.1466A>G (p.Lys489Arg)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99665	NM_003322.6(TULP1):c.1495+1G>A	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
TULP1	Strong	Autosomal recessive	Leber congenital amaurosis 15	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TULP1	Orphanet:65	Leber congenital amaurosis
TULP1	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
TULP1	HGNC:12423	ENSG00000112041	O00294	Tubby-related protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TULP1	Tubby-related protein 1	Required for normal development of photoreceptor synapses.

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)
TULP1	Other/Unknown	no		Tubby_C, Tubby_C_CS, Tubby-like_C

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
primordial germ cell in gonad	1
retina	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TULP1	134	tissue_specific	marker	primordial germ cell in gonad, tendon of biceps brachii, retina

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TULP1	760

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TULP1	O00294	2

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
protein localization to photoreceptor outer segment	1	2407.4×	0.003	TULP1
phagocytosis, recognition	1	2106.5×	0.003	TULP1
retina homeostasis	1	1123.5×	0.003	TULP1
eye photoreceptor cell development	1	842.6×	0.003	TULP1
detection of light stimulus involved in visual perception	1	648.1×	0.003	TULP1
protein localization to cilium	1	401.2×	0.004	TULP1
dendrite development	1	391.9×	0.004	TULP1
photoreceptor cell maintenance	1	358.6×	0.004	TULP1
positive regulation of phagocytosis	1	318.0×	0.004	TULP1
retina development in camera-type eye	1	255.3×	0.004	TULP1
visual perception	1	79.5×	0.013	TULP1

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
TULP1	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	TULP1

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)
TULP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.