CLN8

Chr 8AR

CLN8 transmembrane ER and ERGIC protein

Also known as: C8orf61, EPMR, TLCD6

CLN8 encodes a transmembrane protein that localizes to the endoplasmic reticulum and functions in lipid synthesis, transport, or sensing, with patients showing altered brain sphingolipid and phospholipid levels. Mutations cause neuronal ceroid lipofuscinosis type 8 (CLN8 disease), including the Northern epilepsy variant, characterized by progressive epilepsy with cognitive disabilities. The condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.173 OMIM phenotypes
Clinical SummaryCLN8
🧬
Gene-Disease Validity (ClinGen)
neuronal ceroid lipofuscinosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.004
Z-score 1.22
OE 0.56 (0.291.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.77Z-score
OE missense 1.16 (1.041.31)
200 obs / 171.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.291.17)
00.351.4
Missense OE1.16 (1.041.31)
00.61.4
Synonymous OE1.34
01.21.6
LoF obs/exp: 5 / 8.9Missense obs/exp: 200 / 171.7Syn Z: -2.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCLN8-related neuronal ceroid lipofuscinosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7228th %ile
GOF
0.7126th %ile
LOF
0.2189th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗