CLN8

Chr 8AR

CLN8 transmembrane ER and ERGIC protein

Also known as: C8orf61, EPMR, TLCD6

NCBI Gene: 2055ENSG00000182372UniProt: Q9UBY8OMIM: 607837

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]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 8MIM #600143
AR
Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variantMIM #610003
AR
Ceroid lipofuscinosis, neuronal, 8MIM #600143
AR

Clinical highlights

Gene-disease validity (ClinGen)
neuronal ceroid lipofuscinosis · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
18
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.17
LOEUF
LOF
Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.17LOEUF
pLI 0.004
Z-score 1.22
OE 0.56 (0.29–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.77Z-score
OE missense 1.16 (1.04–1.31)
200 obs / 171.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.56 (0.29–1.17)
0≤0.351.4
Missense OE?1.16 (1.04–1.31)
0≤0.61.4
Synonymous OE?1.34
0≤1.21.6
LoF obs/exp: 5 / 8.9Missense obs/exp: 200 / 171.7Syn Z: -2.34

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CLN8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients