CLN8

Chr 8AR

CLN8 transmembrane ER and ERGIC protein

Also known as: C8orf61, EPMR, TLCD6

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…
LOFmechanismARLOEUF 1.173 OMIM phenotypes
Clinical SummaryCLN8
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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.
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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 OE?0.56 (0.291.17)
00.351.4
Missense OE?1.16 (1.041.31)
00.61.4
Synonymous OE?1.34
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

This gene — mechanism propensity

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.