Leber congenital amaurosis 3

Summary

Leber congenital amaurosis 3 (MONDO:0011415) is a disease caused by SPATA7 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: SPATA7 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 433

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Leber congenital amaurosis 3
Mondo ID	MONDO:0011415
MeSH	C565814
OMIM	604232
DOID	DOID:0110331
UMLS	C1858677
MedGen	346964
GARD	0009661
Is cancer (heuristic)	no

Also known as: amaurosis congenita of Leber, type 3 · LCA3 · Leber congenital amaurosis 3 · Leber congenital amaurosis caused by mutation in SPATA7 · Leber congenital amaurosis type 3 · retinitis pigmentosa, juvenile, autosomal recessive · SPATA7 Leber congenital amaurosis

Data availability: 433 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 3

Related subtypes (20): retinal aplasia, Leber congenital amaurosis 1, Leber congenital amaurosis 2, 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 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

433 retrieved; paginated sample, class counts are floors:

200 uncertain significance, 122 likely benign, 43 pathogenic, 29 conflicting classifications of pathogenicity, 15 benign, 12 likely pathogenic, 6 pathogenic/likely pathogenic, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071024	NC_000014.8:g.(?88852143)(88904786_?)del	SPATA7	Pathogenic	criteria provided, single submitter
1072160	NM_018418.5(SPATA7):c.1210G>T (p.Glu404Ter)	SPATA7	Pathogenic	criteria provided, single submitter
1076482	NM_018418.5(SPATA7):c.265_268del (p.Leu89fs)	SPATA7	Pathogenic	criteria provided, multiple submitters, no conflicts
1076781	NM_018418.5(SPATA7):c.1199_1203del (p.Asn400fs)	SPATA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076992	NC_000014.8:g.(?88852163)(88862567_?)del	SPATA7	Pathogenic	criteria provided, single submitter
1395	NM_018418.5(SPATA7):c.322C>T (p.Arg108Ter)	SPATA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1396	NM_018418.5(SPATA7):c.960dup (p.Pro321fs)	SPATA7	Pathogenic	criteria provided, multiple submitters, no conflicts
1397	NM_018418.5(SPATA7):c.1183C>T (p.Arg395Ter)	SPATA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1398	NM_018418.5(SPATA7):c.1395del (p.Gln465fs)	SPATA7	Pathogenic	no assertion criteria provided
1411536	NM_018418.5(SPATA7):c.969_975del (p.Gly324fs)	SPATA7	Pathogenic	criteria provided, single submitter
1451496	NM_018418.5(SPATA7):c.418dup (p.Met140fs)	SPATA7	Pathogenic	criteria provided, single submitter
1458662	NM_018418.5(SPATA7):c.700dup (p.Ser234fs)	SPATA7	Pathogenic	criteria provided, single submitter
1686226	NM_018418.5(SPATA7):c.19+2T>A	SPATA7	Pathogenic	criteria provided, multiple submitters, no conflicts
1713268	NM_018418.5(SPATA7):c.1418del (p.Met473fs)	SPATA7	Pathogenic	criteria provided, single submitter
1802260	NM_018418.5(SPATA7):c.901_912+1del	SPATA7	Pathogenic	criteria provided, single submitter
191050	NM_018418.5(SPATA7):c.288T>A (p.Cys96Ter)	SPATA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1967922	NM_018418.5(SPATA7):c.578_581dup (p.Ser195fs)	SPATA7	Pathogenic	criteria provided, single submitter
2014731	NM_018418.5(SPATA7):c.864del (p.Thr289fs)	SPATA7	Pathogenic	criteria provided, single submitter
2090160	NM_018418.5(SPATA7):c.1090G>T (p.Glu364Ter)	SPATA7	Pathogenic	criteria provided, single submitter
2093809	NM_018418.5(SPATA7):c.1079_1080del (p.Tyr359_Ser360insTer)	SPATA7	Pathogenic	criteria provided, single submitter
2100961	NM_018418.5(SPATA7):c.477_478del (p.Leu161fs)	SPATA7	Pathogenic	criteria provided, single submitter
236497	NM_018418.5(SPATA7):c.1058dup (p.Ser354fs)	SPATA7	Pathogenic	criteria provided, single submitter
2426472	NC_000014.8:g.(?88852163)(88904766_?)del	SPATA7	Pathogenic	criteria provided, single submitter
2942222	NM_018418.5(SPATA7):c.1222del (p.Met408fs)	SPATA7	Pathogenic	criteria provided, single submitter
30805	SPATA7, 3-BP DEL, 1227CAC	SPATA7	Pathogenic	no assertion criteria provided
30806	NM_018418.5(SPATA7):c.253C>T (p.Arg85Ter)	SPATA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3249373	NM_018418.5(SPATA7):c.487A>T (p.Lys163Ter)	SPATA7	Pathogenic	criteria provided, multiple submitters, no conflicts
3751794	NM_018418.5(SPATA7):c.419del (p.Met140fs)	SPATA7	Pathogenic	criteria provided, single submitter
3759255	NM_018418.5(SPATA7):c.296_297del (p.Glu99fs)	SPATA7	Pathogenic	criteria provided, multiple submitters, no conflicts
3760323	NM_018418.5(SPATA7):c.224del (p.Ser75fs)	SPATA7	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 5 · 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
SPATA7	Definitive	Autosomal recessive	Leber congenital amaurosis 3	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPATA7	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
SPATA7	Orphanet:65	Leber congenital amaurosis
SPATA7	Orphanet:791	Retinitis pigmentosa
TTC8	Orphanet:110	Bardet-Biedl syndrome
TTC8	Orphanet:791	Retinitis pigmentosa

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
SPATA7	HGNC:20423	ENSG00000042317	Q9P0W8	Spermatogenesis-associated protein 7	gencc,clinvar
TTC8	HGNC:20087	ENSG00000165533	Q8TAM2	Tetratricopeptide repeat protein 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPATA7	Spermatogenesis-associated protein 7	Involved in the maintenance of both rod and cone photoreceptor cells.
TTC8	Tetratricopeptide repeat protein 8	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPATA7	Other/Unknown	no		SPATA7
TTC8	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, BBS8

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
left testis	1
right testis	1
sperm	1
adrenal tissue	1
islet of Langerhans	1
left ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPATA7	263	ubiquitous	marker	right testis, sperm, left testis
TTC8	247	ubiquitous	marker	left ovary, islet of Langerhans, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTC8	1,822
SPATA7	757

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TTC8	Q8TAM2	84.48
SPATA7	Q9P0W8	58.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.002	TTC8

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
establishment of anatomical structure orientation	1	8426.0×	0.001	TTC8
protein localization to photoreceptor connecting cilium	1	8426.0×	0.001	SPATA7
sensory processing	1	2808.7×	0.003	TTC8
renal tubule development	1	2106.5×	0.003	TTC8
camera-type eye photoreceptor cell differentiation	1	1685.2×	0.003	TTC8
multi-ciliated epithelial cell differentiation	1	1404.3×	0.003	TTC8
protein localization to photoreceptor outer segment	1	1203.7×	0.003	SPATA7
establishment of planar polarity	1	526.6×	0.005	TTC8
establishment of epithelial cell apical/basal polarity	1	526.6×	0.005	TTC8
regulation of stress fiber assembly	1	495.6×	0.005	TTC8
inner ear receptor cell stereocilium organization	1	421.3×	0.005	TTC8
olfactory bulb development	1	383.0×	0.005	TTC8
photoreceptor cell maintenance	1	179.3×	0.010	SPATA7
non-motile cilium assembly	1	145.3×	0.012	TTC8
regulation of protein localization	1	102.8×	0.016	TTC8
fat cell differentiation	1	90.6×	0.017	TTC8
sensory perception of smell	1	78.0×	0.018	TTC8
multicellular organism growth	1	68.5×	0.019	TTC8
microtubule cytoskeleton organization	1	60.6×	0.021	SPATA7
protein localization to plasma membrane	1	54.4×	0.022	TTC8
axon guidance	1	45.3×	0.025	TTC8
visual perception	1	39.8×	0.027	SPATA7
cilium assembly	1	36.8×	0.028	TTC8
protein transport	1	21.9×	0.045	TTC8

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
SPATA7	0	0
TTC8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SPATA7, TTC8

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)
SPATA7	0	—
TTC8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.