CLN8

CLN8 transmembrane ER and ERGIC protein, the group of TLC domain containing

Basic information

Region (hg38): 8:1755778-1801711

Previous symbols: [ "EPMR", "C8orf61" ]

Links

ENSG00000182372 ∙ NCBI:2055 ∙ OMIM:607837 ∙ HGNC:2079 ∙ Uniprot:Q9UBY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronal ceroid lipofuscinosis 8 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 8 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 8 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 8 northern epilepsy variant (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 8 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 8 northern epilepsy variant (Supportive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 8 (Supportive), mode of inheritance: AR
• autism spectrum disorder (Disputed Evidence), mode of inheritance: AD
• neuronal ceroid lipofuscinosis 8 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ceroid lipofuscinosis, neuronal, 8; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	10508524; 10191125; 11589000; 15024724; 15074367; 16570191; 17129765; 17560505; 19431184; 19807737; 21990111; 22220808; 22964447

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLN8 gene.

• Neuronal_ceroid_lipofuscinosis (468 variants)
• Neuronal_ceroid_lipofuscinosis_8 (163 variants)
• not_provided (109 variants)
• Inborn_genetic_diseases (69 variants)
• not_specified (45 variants)
• Neuronal_ceroid_lipofuscinosis_8_northern_epilepsy_variant (31 variants)
• CLN8-related_disorder (10 variants)
• Intellectual_disability (4 variants)
• Central_core_myopathy (1 variants)
• Seizure (1 variants)
• Neuronal_ceroid_lipofuscinosis_1 (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLN8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018941.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	194		198
missense	3	27	229	11	2	272
nonsense	21	4	3			28
start loss	2	2				4
frameshift	15	12	3			30
splice donor/acceptor (+/-2bp)	1	3	2			6
Total	42	48	241	205	2

Highest pathogenic variant AF is 0.000042136417

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLN8	protein_coding	protein_coding	ENST00000331222	2	30795

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00356	0.853	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.766	200	172	1.16	0.0000108	1879
Missense in Polyphen		59	66.072	0.89296		755
Synonymous	-2.34	102	76.0	1.34	0.00000519	586
Loss of Function	1.22	5	8.95	0.559	3.90e-7	86

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Could play a role in cell proliferation during neuronal differentiation and in protection against cell death. {ECO:0000269|PubMed:19431184}.
• Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 8 (CLN8) [MIM:600143]: A form of neuronal ceroid lipofuscinosis with onset in childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 8 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. {ECO:0000269|PubMed:15024724, ECO:0000269|PubMed:16570191, ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:19431184, ECO:0000269|PubMed:19807737, ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:26443629}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8NE) [MIM:610003]: A form of neuronal ceroid lipofuscinosis clinically characterized by epilepsy that presents between 5 and 10 years of age with frequent tonic-clonic seizures followed by progressive mental retardation. Visual loss is not a prominent feature. Intracellular accumulation of autofluorescent material results in curvilinear and granular profiles on ultrastructural analysis. {ECO:0000269|PubMed:10508524, ECO:0000269|PubMed:21990111}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Synaptic Vesicle Pathway (Consensus)

Intolerance Scores

• loftool: 0.142
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.132
• hipred: N
• hipred_score: 0.251
• ghis: 0.501

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.160

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cln8
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: age-dependent response to oxidative stress;phospholipid metabolic process;ceramide metabolic process;lipid transport;mitochondrial membrane organization;lysosome organization;nervous system development;visual perception;adult walking behavior;cholesterol metabolic process;associative learning;regulation of cell size;lipid biosynthetic process;somatic motor neuron differentiation;protein catabolic process;social behavior;negative regulation of apoptotic process;cellular protein catabolic process;photoreceptor cell maintenance;negative regulation of proteolysis;ceramide biosynthetic process;musculoskeletal movement;neuromuscular process controlling posture;neuromuscular process controlling balance;glutamate reuptake;retina development in camera-type eye;neurofilament cytoskeleton organization
• Cellular component: mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;endoplasmic reticulum-Golgi intermediate compartment;integral component of membrane;endoplasmic reticulum-Golgi intermediate compartment membrane;presynapse