GeneBe

CLN6

CLN6 transmembrane ER protein

Basic information

Region (hg38): 15:68206992-68257211

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, 6A (Definitive), 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, 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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ceroid lipofuscinosis, neuronal, 6A; Ceroid lipofuscinosis, neuronal, 6BARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingBiochemical; Neurologic; Ophthalmologic13822848; 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 (607 variants)
  • not_provided (157 variants)
  • Ceroid_lipofuscinosis,_neuronal,_6A (109 variants)
  • Ceroid_lipofuscinosis,_neuronal,_6B_(Kufs_type) (61 variants)
  • Inborn_genetic_diseases (60 variants)
  • not_specified (59 variants)
  • CLN6-related_disorder (10 variants)
  • Adult_neuronal_ceroid_lipofuscinosis (7 variants)
  • See_cases (3 variants)
  • Abnormality_of_the_nervous_system (3 variants)
  • Neurodevelopmental_disorder (2 variants)
  • Abnormal_brain_morphology (1 variants)
  • Agenesis_of_the_corpus_callosum_with_peripheral_neuropathy (1 variants)
  • Neuronal_Ceroid-Lipofuscinosis,_Recessive (1 variants)
  • Spastic_ataxia (1 variants)
  • Cystic_fibrosis (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. These statistics are base on transcript: NM_000017882.3. 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.

EffectPLPVUSLBBSum
synonymous
218
clinvar
 218
missense
7
clinvar
38
clinvar
191
clinvar
14
clinvar
1
clinvar
 251
nonsense
17
clinvar
8
clinvar
1
clinvar
 26
start loss
2
2
 4
frameshift
29
clinvar
13
clinvar
1
clinvar
 43
splice donor/acceptor (+/-2bp)
2
clinvar
18
clinvar
 20
Total 57 79 193 232 1

Highest pathogenic variant AF is 0.00007322608

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CLN6protein_codingprotein_codingENST00000249806 750220
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.0001000.8181257060421257480.000167
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.009221761761.000.00001182031
Missense in Polyphen6377.4510.81342932
Synonymous-2.5310274.31.370.00000525633
Loss of Function1.23812.70.6285.62e-7149

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005820.000582
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.0001410.000141
Middle Eastern0.00005440.0000544
South Asian0.0001630.000163
Other0.0001630.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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