LCA5

Chr 6AR

lebercilin LCA5

Also known as: C6orf152

NCBI Gene: 167691ENSG00000135338UniProt: Q86VQ0

This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Leber congenital amaurosis 5MIM #604537
AR
Leber congenital amaurosis 5MIM #604537
AR
193
ClinVar variants
35
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— LCA5
🧬
Gene-Disease Validity (ClinGen)
LCA5-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 70 VUS of 193 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.000
Z-score 3.09
OE 0.41 (0.27–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.62Z-score
OE missense 1.10 (1.00–1.19)
370 obs / 337.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.27–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.00–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 13 / 31.8Missense obs/exp: 370 / 337.9Syn Z: -1.14

ClinVar Variant Classifications

193 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic16
VUS70
Likely Benign88
19
Pathogenic
16
Likely Pathogenic
70
VUS
88
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
9
0
19
Likely Pathogenic
7
2
7
0
16
VUS
0
61
1
8
70
Likely Benign
0
1
30
57
88
Benign
0
0
0
0
0
Total17644765193

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LCA5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LCA5-related Leber congenital amaurosis

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Leber congenital amaurosis 5

MIM #604537

Molecular basis of disorder known

Autosomal recessive
LEBERILIN LCA5; LCA5
MIM #611408 · *

Leber congenital amaurosis 5

MIM #604537

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — LCA5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids.
Athanasiou D et al.·Acta Neuropathol Commun
2025
Genetic and Clinical Profile of Retinopathies Due to Disease-Causing Variants in Leber Congenital Amaurosis (LCA)-Associated Genes in a Large German Cohort.
Zobor D et al.·Int J Mol Sci
2023Cohort
Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis.
Zhou Y et al.·Graefes Arch Clin Exp Ophthalmol
2024Cohort
Involvement of LCA5 in Leber congenital amaurosis and retinitis pigmentosa in the Spanish population.
Corton M et al.·Ophthalmology
2014
Phenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes.
Akhtar Z et al.·Genes (Basel)
2024Cohort
Progression of phenotype in Leber's congenital amaurosis with a mutation at the LCA5 locus.
Mohamed MD et al.·Br J Ophthalmol
2003
Screening of a large cohort of leber congenital amaurosis and retinitis pigmentosa patients identifies novel LCA5 mutations and new genotype-phenotype correlations.
Mackay DS et al.·Hum Mutat
2013Cohort
Prenatal detection of pure proximal 6q14.1 microduplication encompassing LCA5 gene: A variant of likely benign.
Yue F et al.·Medicine (Baltimore)
2022
Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: retained photoreceptors adjacent to retinal disorganization.
Jacobson SG et al.·Mol Vis
2009
LCA5, a rare genetic cause of leber congenital amaurosis in Koreans.
Seong MW et al.·Ophthalmic Genet
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
LCA5

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients

RECRUITING
NCT05616793Phase PHASE1, PHASE2Opus Genetics, IncStarted 2023-06-15
AAV8.hLCA5

External Resources

Links to major genomics databases and tools