CLN8 CLN8 transmembrane ER and ERGIC protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLN8provided by HGNC
Official Full Name: CLN8 transmembrane ER and ERGIC proteinprovided by HGNC
Primary source: HGNC:HGNC:2079
See related: Ensembl:ENSG00000182372 MIM:607837; AllianceGenome:HGNC:2079
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: EPMR; TLCD6; C8orf61
Summary: This gene encodes a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with a disorder characterized by progressive epilepsy with cognitive disabilities (EPMR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain. [provided by RefSeq, Jul 2017]
Expression: Ubiquitous expression in brain (RPKM 5.7), spleen (RPKM 4.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8p23.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (1753059..1786570)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (1542478..1565133)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (1711955..1734736)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CLN8 Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis-Literature Review and Case Report.
Title: CLN8 Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis-Literature Review and Case Report.
miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage.
Title: miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage.
The Neuronal Ceroid Lipofuscinoses-Linked Loss of Function CLN5 and CLN8 Variants Disrupt Normal Lysosomal Function.
Title: The Neuronal Ceroid Lipofuscinoses-Linked Loss of Function CLN5 and CLN8 Variants Disrupt Normal Lysosomal Function.
CLN8 associates with CLN6 to form the EGRESS complex (ER-to-Golgi Relaying of Enzymes of the lySosomal System), the functional unit responsible for the recruitment of newly synthesized lysosomal enzymes in the endoplasmic reticulum and their transfer to the Golgi complex.
Title: A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer.
the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3beta, were decreased in CLN8 disease patient fibroblasts.
Title: Neuronal ceroid lipofuscinosis related ER membrane protein CLN8 regulates PP2A activity and ceramide levels.
CLN8 recruits lysosomal soluble proteins in the endoplasmic reticulum (ER), delivers them to the Golgi apparatus via COPII-coated vesicles, and recycles back to the ER via COPI-coated vesicles. CLN8 interacts with the lysosomal soluble proteins through its large luminal loop. The export signal of CLN8 (261VDWNF265) is localized in its cytosolic C-terminus. CLN8 deficiency results in depletion of enzymes at the lysosome.
Title: CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis.
Whole-exome sequencing and homozygosity mapping revealed a novel homozygous CLN8 mutation, c.677T>C (p.Leu226Pro in 5 relatives from a large Turkish consanguineous family
Title: Exome sequencing identifies a novel homozygous CLN8 mutation in a Turkish family with Northern epilepsy.
Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis
Title: Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: The first report of a CLN8 mutation in Japan.
This study does not support a contribution of rare missense CLN8 variations to ASD susceptibility in the Japanese population.
Title: Resequencing and Association Analysis of CLN8 with Autism Spectrum Disorder in a Japanese Population.
This study highlights a close interaction between CLN5/CLN8 proteins, and their role in sphingolipid metabolism. Our findings suggest that CLN5p/CLN8p most likely are positive modulators of CerS1 and/or CerS2.
Title: CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neuronal ceroid lipofuscinosis 8 MedGen: C1838570 OMIM: 600143 GeneReviews: Not available	Compare labs
Neuronal ceroid lipofuscinosis 8 northern epilepsy variant MedGen: C1864923 OMIM: 610003 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-148543 (e-PCR)
- UniSTS:176452

GDB:315881 (e-PCR)
- UniSTS:156545

RH47694 (e-PCR)
- UniSTS:2732

RH80031 (e-PCR)
- UniSTS:91103

AFM265wb5 (e-PCR)
- UniSTS:7669

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ceramide binding	IBA Inferred from Biological aspect of Ancestor more info
enables ceramide binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within adult locomotory behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within adult walking behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within associative learning	IEA Inferred from Electronic Annotation more info
involved_in ceramide biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in ceramide metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glutamate reuptake	IEA Inferred from Electronic Annotation more info
involved_in lipid biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in lipid homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in lipid transport	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within lysosome organization	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within macromolecule catabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within mitochondrial membrane organization	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within musculoskeletal movement	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of proteolysis	NAS Non-traceable Author Statement more info	PubMed
involved_in nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neurofilament cytoskeleton organization	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neuromuscular process controlling posture	IEA Inferred from Electronic Annotation more info
acts_upstream_of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in phospholipid metabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within phospholipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in phospholipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within photoreceptor cell maintenance	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within regulation of cell size	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within retina development in camera-type eye	IEA Inferred from Electronic Annotation more info
acts_upstream_of retinal rod cell apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within social behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within somatic motor neuron differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within spinal cord motor neuron differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
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	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum-Golgi intermediate compartment membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in presynapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein CLN8

Names: ceroid-lipofuscinosis, neuronal 8

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.