CLN6 CLN6 transmembrane ER protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLN6provided by HGNC
Official Full Name: CLN6 transmembrane ER proteinprovided by HGNC
Primary source: HGNC:HGNC:2077
See related: Ensembl:ENSG00000128973 MIM:606725; AllianceGenome:HGNC:2077
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: nclf; CLN4A; CLN6A; HsT18960
Summary: 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]
Expression: Ubiquitous expression in bone marrow (RPKM 12.1), colon (RPKM 10.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q23

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (68206992..68257211, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (66025741..66075904, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (68499330..68549549, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families.
Title: Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families.
Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience.
Title: Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience.
CLN6's luminal tail-mediated functional interference between CLN6 mutants as a novel pathomechanism for the neuronal ceroid lipofuscinoses.
Title: CLN6's luminal tail-mediated functional interference between CLN6 mutants as a novel pathomechanism for the neuronal ceroid lipofuscinoses.
p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis.
Title: p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis.
Implications of graded reductions in CLN6's anti-aggregate activity for the development of the neuronal ceroid lipofuscinoses.
Title: Implications of graded reductions in CLN6's anti-aggregate activity for the development of the neuronal ceroid lipofuscinoses.
The CLN6 protein associates with the CLN8 protein to form the EGRESS complex (ER-to-Golgi Relaying of Enzymes of the lySosomal System), which mediates ER exit and Golgi transfer of newly synthesized lysosomal enzymes. The second luminal loop of CLN6 is required for the interaction of CLN6 with the enzymes. Loss-of-function mutations in CLN6 affect enzyme trafficking and result in lower levels of enzymes at the lysosome.
Title: A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer.
compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T are possibly the genetic causes of the autosomal recessive neuronal ceroid lipofuscinoses
Title: [Genetic study of a family of neuronal ceroid lipofuscinosis caused by a heterozygous mutation of CLN6 gene].
Clinical distinction of type A (progressive myoclonus epilepsy) and type B (dementia with motor disturbance) Kufs disease was supported by molecular diagnoses. Type A is usually caused by recessive pathogenic variants in CLN6 or dominant variants in DNAJC5. Type B Kufs is usually associated with recessive CTSF pathogenic variants.
Title: Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.
Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment
Title: Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.
The CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMalphaBC, but also serves as a potential target of therapeutic interventions.
Title: Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Ceroid lipofuscinosis, neuronal, 6A MedGen: C5551375 OMIM: 601780 GeneReviews: Not available	not available
Ceroid lipofuscinosis, neuronal, 6B (Kufs type) MedGen: C5561927 OMIM: 204300 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 is identified to have a physical interaction with ceroid-lipofuscinosis, neuronal 6, late infantile, variant (CLN6) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

L18426 (e-PCR)
- UniSTS:34648

WI-11786 (e-PCR)
- UniSTS:48491

D1S1423 (e-PCR)
- UniSTS:149619

STS-W81097 (e-PCR)
- UniSTS:54398

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables lysophosphatidic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables sulfatide binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cholesterol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ganglioside metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glycosaminoglycan metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotion involved in locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in lysosomal lumen acidification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lysosome organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum lumen	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	HDA more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: ceroid-lipofuscinosis neuronal protein 6

Names: ceroid-lipofuscinosis neuronal 6 late infantile; ceroid-lipofuscinosis, neuronal 6, late infantile

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.