CLN5

Chr 13AR

CLN5 lysosomal BMP synthase

NCBI Gene: 1203ENSG00000102805UniProt: O75503

This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function.[provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 5MIM #256731
AR
Ceroid lipofuscinosis, neuronal, 5MIM #256731
AR
697
ClinVar variants
173
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— CLN5
🧬
Gene-Disease Validity (ClinGen)
neuronal ceroid lipofuscinosis · 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
173 Pathogenic / Likely Pathogenic· 245 VUS of 697 total submissions
💊
Clinical Trials
2 active or recruiting trials — 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.
1.23LOEUF
pLI 0.000
Z-score 0.85
OE 0.78 (0.52–1.23)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.12Z-score
OE missense 1.02 (0.92–1.14)
226 obs / 220.8 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.0.78 (0.52–1.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.92–1.14)
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.0.91
0≤1.21.6
LoF obs/exp: 14 / 17.9Missense obs/exp: 226 / 220.8Syn Z: 0.67

ClinVar Variant Classifications

697 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic108
Likely Pathogenic65
VUS245
Likely Benign242
Benign4
Conflicting33
108
Pathogenic
65
Likely Pathogenic
245
VUS
242
Likely Benign
4
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
1
80
0
108
Likely Pathogenic
41
5
19
0
65
VUS
4
177
63
1
245
Likely Benign
0
2
84
156
242
Benign
0
0
4
0
4
Conflicting
—33
Total72185250157697

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

View in ClinVar →

Protein Context — Lollipop Plot

CLN5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CLN5-related neuronal ceroid lipofuscinosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Ceroid lipofuscinosis, neuronal, 5

MIM #256731

Molecular basis of disorder known

Autosomal recessive

Ceroid lipofuscinosis, neuronal, 5

MIM #256731

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CLN5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.
Kousi M et al.·Hum Mutat
2012Review
A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis.
Basak I et al.·Cell Mol Life Sci
2021Review
CLN5 deficiency impairs glucose uptake and uncovers PHGDH as a potential biomarker in Batten disease.
Marchese M et al.·Mol Psychiatry
2025
The neuronal ceroid-lipofuscinoses.
Goebel HH·Semin Pediatr Neurol
1996Review
The neuronal ceroid-lipofuscinoses.
Goebel HH·J Child Neurol
1995Review
Studies of homogenous populations: CLN5 and CLN8.
Ranta S et al.·Adv Genet
2001Review
The Neuronal Ceroid Lipofuscinoses-Linked Loss of Function CLN5 and CLN8 Variants Disrupt Normal Lysosomal Function.
Parvin S et al.·Neuromolecular Med
2019Case report
Human pathology in NCL.
Anderson GW et al.·Biochim Biophys Acta
2013Review
CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.
Haddad SE et al.·Electrophoresis
2012
Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease).
Mitchell NL et al.·Dev Neurobiol
2023
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
Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING
NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08
Natural History
Neuronal Ceroid Lipofuscinosis CLN5

Gene Therapy Study for Children With CLN5 Batten Disease

ACTIVE NOT RECRUITING
NCT05228145Phase PHASE1, PHASE2Neurogene Inc.Started 2022-01-31
NGN-101

External Resources

Links to major genomics databases and tools