Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

CLN3

CLN3 lysosomal/endosomal transmembrane protein, battenin

The CLN3 gene encodes a transmembrane protein, battenin, primarily located in lysosomes, which are critical for cellular waste processing and recycling. The CLN3 gene provides instructions for producing the battenin protein, essential for the proper functioning of lysosomes within cells.

Chromosome 16p12.1 Autosomal recessive HGNC:2074 Tier C
CLN3 16p12.1 p arm q arm 16

CLN3 is located on the short (p) arm of chromosome 16, at band 16p12.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 16 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
CLN3 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The CLN3 gene, also known as battenin, provides the genetic blueprint for a protein found throughout the body's tissues. This protein is predominantly located in the membranes of lysosomes, which are cellular compartments responsible for breaking down and recycling various molecules. While the exact function of the CLN3 protein is not fully understood, it is thought to facilitate communication between lysosomes and the rest of the cell.

Disruptions to the CLN3 gene are primarily linked to Neuronal Ceroid Lipofuscinosis 3, an inherited neurological disorder.

What the gene does

The CLN3 protein is a transmembrane protein within lysosomes, which are vital for cellular digestion and waste recycling. Research indicates that the CLN3 protein is involved in multiple cellular functions. These include autophagy, which is the process of recycling worn-out cellular components, and the maintenance of lysosomal acidity (pH).

The protein also plays a role in endocytosis, which is the uptake of molecules from outside the cell, and the trafficking of other proteins to their correct cellular locations. Additionally, CLN3 has been associated with programmed cell death (apoptosis), cell proliferation, and osmoregulation. While these diverse roles suggest a broad impact on cellular health, it is currently unclear which of these functions represents the primary role of the CLN3 protein, or if some are secondary effects of its core activity.

Video: Genetics 101

Chromosome location

The CLN3 gene is situated on the short arm of chromosome 16 at position 12.1, denoted as 16p12.1. This genomic location specifies where the gene resides within the human genome.

Protein structure

The CLN3 protein, which is 438 amino acids long, features several distinct regions and motifs. It contains two Disordered regions, spanning amino acids 1-25 and 237-268. Within these, specific Lysosomal targeting motifs are identified at amino acids 242-244, 253-254, and 409-419. The motif at amino acids 253-254 is particularly noted for being required for interaction with AP1G1, AP2A2, and AP3D1 proteins, which are involved in protein trafficking.

Domain map · 438 amino acids
Lysosomal targeting motif (242–244)Lysosomal targeting motif. Required for AP1G1, AP2A2 and AP3D1 interaction (253–254)Lysosomal targeting motif (409–419)Lysosomal targeting mo242–244Lysosomal targeting mo253–254Lysosomal targeting mo409–4191~219438
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:Q13286Length:438 aaStructure:AlphaFold

Key variants

Variants within the CLN3 gene can lead to alterations in the battenin protein, impacting its normal function. More than 65 different pathogenic variants in CLN3 have been identified. These genetic changes can range from small alterations to larger deletions, affecting the protein's structure and its ability to participate in cellular processes.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for CLN3.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1115_1118dup
Duplication
 p.Val374fs Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis 3
c.126G>A
single nucleotide variant
 p.Trp42Ter Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis
c.379dup
Duplication
 p.Arg127fs Pathogenic/Likely pathogenic ★★☆☆ Juvenile neuronal ceroid lipofuscinosis
c.3G>A
single nucleotide variant
 p.Met1Ile Pathogenic/Likely pathogenic ★★☆☆ Juvenile neuronal ceroid lipofuscinosis
c.461-2A>G
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis
c.551G>A
single nucleotide variant
 p.Trp184Ter Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis
c.552G>A
single nucleotide variant
 p.Trp184Ter Pathogenic/Likely pathogenic ★★☆☆ Juvenile neuronal ceroid lipofuscinosis
c.729del
Deletion
 p.Glu244fs Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis
c.849G>A
single nucleotide variant
 p.Trp283Ter Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis
c.944_945insGA
Insertion
 p.His315fs Pathogenic/Likely pathogenic ★★☆☆ Neuronal ceroid lipofuscinosis

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the CLN3 gene are primarily associated with Neuronal ceroid lipofuscinosis 3, also known as Batten disease. This inherited disorder typically manifests in childhood, leading to progressive neurological decline. Individuals with this condition may experience worsening vision impairment, intellectual disability, difficulties with movement, speech problems, and seizures. In some cases, CLN3 variants can also cause vision impairment without the other classic signs of Batten disease, a condition known as CLN3-associated isolated retinal degeneration.

  • Neuronal ceroid lipofuscinosis 3 (Batten, CLN3)
    IEM
    AR
    Dedicated page coming soon

Inheritance pattern

Conditions caused by pathogenic CLN3 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous CLN3 carrier status across ancestry groups?

UK clinical status

The CLN3 gene is included in several testing panels within the UK NHS Genomic Medicine Service via PanelApp. It is assessed for conditions such as Dystonia, chorea or related movement disorder (R57), Early onset or syndromic epilepsy, Intellectual disability, and Likely inborn error of metabolism (R98). CLN3 is also relevant for Lysosomal storage disorder (R276), Neuronal ceroid lipofuscinosis (R231), Retinal disorders (R32), and Undiagnosed metabolic disorders, indicating its established clinical significance within the UK healthcare system.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Dystonia, chorea or related movement disorder, childhood onset · R57 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Lysosomal storage disorder · R276 NHS GMS → Neuronal ceroid lipofuscinosis · R231 NHS GMS → Retinal disorders · R32 NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the CLN3 gene?

The CLN3 gene provides instructions for the battenin protein, which is mainly found in lysosomes. This protein is thought to play a role in several cellular processes, including the recycling of cellular waste and maintaining the correct acidity within lysosomes.

What health conditions are associated with variants in the CLN3 gene?

Variants in the CLN3 gene are primarily associated with Neuronal ceroid lipofuscinosis 3, also known as Batten disease, which is a severe neurological disorder affecting children. In some instances, it can also cause isolated vision impairment.

Is CLN3 disease an inherited condition?

Yes, CLN3 disease is an inherited disorder. It follows an autosomal recessive inheritance pattern, meaning a person must inherit two copies of the altered gene (one from each parent) to develop the condition.

References

  1. Mirza M, Vainshtein A, DiRonza A. The CLN3 gene and protein: What we know. Molecular genetics & genomic medicine. 2019. PMID: 31568712
  2. Ku CA, Hull S, Arno G. Detailed Clinical Phenotype and Molecular Genetic Findings in CLN3-Associated Isolated Retinal Degeneration. JAMA ophthalmology. 2017. PMID: 28542676
  3. Oetjen S, Kuhl D, Hermey G. Revisiting the neuronal localization and trafficking of CLN3 in juvenile neuronal ceroid lipofuscinosis. Journal of neurochemistry. 2016. PMID: 27453211
  4. Cárcel-Trullols J, Kovács AD, Pearce DA. Cell biology of the NCL proteins: What they do and don't do. Biochimica et biophysica acta. 2015. PMID: 25962910
  5. Uusi-Rauva K, Kyttälä A, van der Kant R. Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments. Cellular and molecular life sciences : CMLS. 2012. PMID: 22261744
  6. Cotman SL, Staropoli JF. The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking. Clinical lipidology. 2012. PMID: 22545070
  7. Kitzmüller C, Haines RL, Codlin S. A function retained by the common mutant CLN3 protein is responsible for the late onset of juvenile neuronal ceroid lipofuscinosis. Human molecular genetics. 2008. PMID: 17947292
  8. Rakheja D, Narayan SB, Bennett MJ. The function of CLN3P, the Batten disease protein. Molecular genetics and metabolism. 2008. PMID: 18688960
  9. Phillips SN, Benedict JW, Weimer JM. CLN3, the protein associated with batten disease: structure, function and localization. Journal of neuroscience research. 2005. PMID: 15657902
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .