CLN5

Chr 13

CLN5 lysosomal BMP synthase

NCBI Gene: 1203 ENSG00000102805 UniProt: O75503

The CLN5 protein functions in lysosomal degradation of post-translationally modified proteins. Mutations cause neuronal ceroid lipofuscinosis type 5 (CLN5 disease), a form of Batten disease characterized by autosomal recessive inheritance and progressive neurodegeneration in children. The disease results from loss-of-function mutations that disrupt lysosomal storage function, leading to accumulation of lipofuscin and other cellular debris.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.23

Clinical Summary— CLN5

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Gene-Disease Validity (ClinGen)

neuronal ceroid lipofuscinosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

160 unique Pathogenic / Likely Pathogenic· 272 VUS of 785 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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GeneReview available — CLN5

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.12Z-score

OE missense 1.02 (0.92–1.14)

226 obs / 220.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.52–1.23)

0≤0.351.4

Missense OE?1.02 (0.92–1.14)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 14 / 17.9Missense obs/exp: 226 / 220.8Syn Z: 0.67

ClinVar Variant Classifications

785 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63

Likely Pathogenic97

VUS272

Likely Benign296

Benign15

Conflicting39

Pathogenic

Likely Pathogenic

272

VUS

296

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	56	1	6	0	63
Likely Pathogenic	83	11	3	0	97
VUS	7	206	58	1	272
Likely Benign	0	4	100	192	296
Benign	0	0	15	0	15
Conflicting	—				39
Total	146	222	182	193	782

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

View in ClinVar →

74 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap CLN5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →