CLN6

CLN6 transmembrane ER protein

Basic information

Region (hg38): 15:68206991-68257211

Links

ENSG00000128973 ∙ NCBI:54982 ∙ OMIM:606725 ∙ HGNC:2077 ∙ Uniprot:Q9NWW5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ceroid lipofuscinosis, neuronal, 6A (Definitive), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6A (Strong), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6B (Kufs type) (Strong), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6B (Kufs type) (Supportive), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6A (Supportive), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6A (Definitive), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6A (Definitive), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6B (Kufs type) (Definitive), mode of inheritance: AR
• ceroid lipofuscinosis, neuronal, 6A (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, 6A; Ceroid lipofuscinosis, neuronal, 6B	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	13822848; 5478271; 760366; 3284607; 7668317; 10929274; 11791207; 11727201; 15965709; 15996215; 19520283; 21549341; 21990111; 22883287; 23180398; 23735787; 30561534

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLN6 gene.

• Neuronal ceroid lipofuscinosis (545 variants)
• not provided (154 variants)
• Ceroid lipofuscinosis, neuronal, 6A (66 variants)
• not specified (59 variants)
• Inborn genetic diseases (46 variants)
• Ceroid lipofuscinosis, neuronal, 6B (Kufs type) (13 variants)
• Ceroid lipofuscinosis, neuronal, 6A;Ceroid lipofuscinosis, neuronal, 6B (Kufs type) (13 variants)
• Ceroid lipofuscinosis, neuronal, 6B (Kufs type);Ceroid lipofuscinosis, neuronal, 6A (7 variants)
• Neuronal Ceroid-Lipofuscinosis, Recessive (7 variants)
• Ceroid lipofuscinosis, neuronal, 6A;Adult neuronal ceroid lipofuscinosis (6 variants)
• See cases (3 variants)
• Abnormality of the nervous system (3 variants)
• Neurodevelopmental disorder (2 variants)
• Abnormal brain morphology (1 variants)
• Adult neuronal ceroid lipofuscinosis;Ceroid lipofuscinosis, neuronal, 6A (1 variants)
• - (1 variants)
• Spastic ataxia (1 variants)
• CLN6-related condition (1 variants)
• Agenesis of the corpus callosum with peripheral neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLN6 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				160		160
missense	3	11	181	5		200
nonsense	11	8	1			20
start loss	1	2				3
frameshift	18	10	1			29
inframe indel	1	1	6			8
splice donor/acceptor (+/-2bp)	1	11				12
splice region			10	21	2	33
non coding	1	2	34	81	18	136
Total	36	45	223	246	18

Highest pathogenic variant AF is 0.000230

Variants in CLN6

This is a list of pathogenic ClinVar variants found in the CLN6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-68207031-C-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207037-C-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207117-C-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207125-A-G		Neuronal ceroid lipofuscinosis	Benign (Jan 12, 2018)
15-68207149-G-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207206-C-A		Neuronal ceroid lipofuscinosis	Likely benign (Jan 13, 2018)
15-68207253-C-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 12, 2018)
15-68207258-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 12, 2018)
15-68207323-G-A		Neuronal ceroid lipofuscinosis	Benign (Jan 12, 2018)
15-68207391-A-G		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 12, 2018)
15-68207415-G-A		Neuronal ceroid lipofuscinosis	Benign (Jan 13, 2018)
15-68207450-T-C		Neuronal ceroid lipofuscinosis	Benign (Jan 13, 2018)
15-68207473-C-T		Neuronal ceroid lipofuscinosis	Benign (Jan 13, 2018)
15-68207485-G-A		Neuronal ceroid lipofuscinosis	Likely benign (Jan 13, 2018)
15-68207494-G-C		Neuronal ceroid lipofuscinosis	Likely benign (Jan 13, 2018)
15-68207608-A-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 12, 2018)
15-68207614-T-C		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207659-A-C		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207670-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 12, 2018)
15-68207694-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 12, 2018)
15-68207747-C-T		Neuronal ceroid lipofuscinosis	Likely benign (May 23, 2021)
15-68207795-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207828-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207840-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)
15-68207856-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLN6	protein_coding	protein_coding	ENST00000249806	7	50220

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000100	0.818	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.00922	176	176	1.00	0.0000118	2031
Missense in Polyphen		63	77.451	0.81342		932
Synonymous	-2.53	102	74.3	1.37	0.00000525	633
Loss of Function	1.23	8	12.7	0.628	5.62e-7	149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000582	0.000582
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 6 (CLN6) [MIM:601780]: A form of neuronal ceroid lipofuscinosis. 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 6 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. {ECO:0000269|PubMed:11727201, ECO:0000269|PubMed:11791207, ECO:0000269|PubMed:12673792, ECO:0000269|PubMed:12815591, ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:21990111, ECO:0000269|Ref.2}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ceroid lipofuscinosis, neuronal, 4A (CLN4A) [MIM:204300]: An adult-onset neuronal ceroid lipofuscinosis. 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. CLN4A has no visual involvement and is characterized by progressive myoclonic epilepsy. {ECO:0000269|PubMed:21549341}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.205

Intolerance Scores

• loftool: 0.171
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• pHI: 0.217
• hipred: N
• hipred_score: 0.443
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.599

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cln6
• Phenotype: hematopoietic 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); skeleton 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); vision/eye phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: ganglioside metabolic process;lysosome organization;lysosomal lumen acidification;visual perception;cholesterol metabolic process;protein catabolic process;glycosaminoglycan metabolic process;locomotion involved in locomotory behavior;cellular macromolecule catabolic process;positive regulation of proteolysis
• Cellular component: endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: protein binding;protein homodimerization activity