CLN8

Protein identityUniProt · HPA

UniProt accession

Q9UBY8

Gene

CLN8

Ensembl

ENSG00000182372

Chromosome

8

Canonical length

286 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

286 residues, UniProt reviewed canonical sequence.

>Q9UBY8|CLN8
     1  MNPASDGGTS ESIFDLDYAS WGIRSTLMVA GFVFYLGVFV VCHQLSSSLN ATYRSLVARE
    61  KVFWDLAATR AVFGVQSTAA GLWALLGDPV LHADKARGQQ NWCWFHITTA TGFFCFENVA
   121  VHLSNLIFRT FDLFLVIHHL FAFLGFLGCL VNLQAGHYLA MTTLLLEMST PFTCVSWMLL
   181  KAGWSESLFW KLNQWLMIHM FHCRMVLTYH MWWVCFWHWD GLVSSLYLPH LTLFLVGLAL
   241  LTLIINPYWT HKKTQQLLNP VDWNFAQPEA KSRPEGNGQL LRKKRP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLN8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

5

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLN8.

Disease | AllUniProt

Conditions CLN8 is implicated in, by any mechanism.

• Ceroid lipofuscinosis, neuronal, 8 (CLN8) MIM:600143
• Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8NE) MIM:610003

Disease | GeneticClinVar

89 pathogenic / likely-pathogenic of 604 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neuronal ceroid lipofuscinosis
• Neuronal ceroid lipofuscinosis 8
• Neuronal ceroid lipofuscinosis 8 northern epilepsy variant
• Inborn genetic diseases
• CLN8-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.17

gnomAD pLI

0

gnomAD missense Z

-0.77

DepMap mean gene effect

0.22

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult walking behavior
• associative learning
• ceramide biosynthetic process
• ceramide metabolic process
• cholesterol metabolic process
• glutamate reuptake
• lipid biosynthetic process
• lipid homeostasis
• lipid transport
• lysosome organization
• mitochondrial membrane organization
• musculoskeletal movement
• negative regulation of neuron apoptotic process
• negative regulation of proteolysis
• nervous system development
• neurofilament cytoskeleton organization
• neuromuscular process controlling balance
• neuromuscular process controlling posture
• phospholipid metabolic process
• photoreceptor cell maintenance
• protein catabolic process
• regulation of cell size
• retina development in camera-type eye
• retinal rod cell apoptotic process
• social behavior
• somatic motor neuron differentiation
• visual perception

Molecular functions

• ceramide binding

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• endoplasmic reticulum-Golgi intermediate compartment
• endoplasmic reticulum-Golgi intermediate compartment membrane
• membrane
• mitochondrion
• presynapse

Protein domainsUniProt · Pfam · InterPro

• TRAM/LAG1/CLN8 homology domain
• TLC domain-containing
• TLC domain

KeywordsUniProt

• Endoplasmic reticulum
• Epilepsy
• Intellectual disability
• Membrane
• Neurodegeneration
• Neuronal ceroid lipofuscinosis
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CLN8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLN3
• CLN5