CLN5

CLN5 intracellular trafficking protein

Basic information

Region (hg38): 13:76990660-77019143

Links

ENSG00000102805 ∙ NCBI:1203 ∙ OMIM:608102 ∙ HGNC:2076 ∙ Uniprot:O75503 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronal ceroid lipofuscinosis 5 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 5 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 5 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 5 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 5 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 5 (Supportive), 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, 5	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	7133332; 1649978; 9662406; 15965709; 15728307; 17607606; 19309691; 20157158; 25359263

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLN5 gene.

• Neuronal_ceroid_lipofuscinosis (473 variants)
• Neuronal_ceroid_lipofuscinosis_5 (177 variants)
• not_provided (94 variants)
• Inborn_genetic_diseases (59 variants)
• not_specified (38 variants)
• Neuronal_Ceroid-Lipofuscinosis,_Dominant/Recessive (8 variants)
• CLN5-related_disorder (4 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Retinal_dystrophy (1 variants)
• Intellectual_disability (1 variants)
• Pontocerebellar_hypoplasia_type_2D (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLN5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006493.4. 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		1	1	166		168
missense	1	22	182	3	2	210
nonsense	18	21	1			40
start loss			2			2
frameshift	35	42	2			79
splice donor/acceptor (+/-2bp)	2	10				12
Total	56	96	188	169	2

Highest pathogenic variant AF is 0.000084883

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLN5	protein_coding	protein_coding	ENST00000377453	4	11858

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.71e-8	0.409	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.123	226	221	1.02	0.0000103	2629
Missense in Polyphen		68	84.975	0.80023		1029
Synonymous	0.671	76	83.8	0.907	0.00000393	784
Loss of Function	0.846	14	17.9	0.784	9.09e-7	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000498	0.000498
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000247	0.000237
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in influencing the retrograde trafficking of lysosomal sorting receptors SORT1 and IGF2R from the endosomes to the trans-Golgi network by controlling the recruitment of retromer complex to the endosomal membrane. Regulates the localization and activation of RAB7A which is required to recruit the retromer complex to the endosomal membrane (PubMed:22431521). {ECO:0000269|PubMed:22431521}.
• Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 5 (CLN5) [MIM:256731]: 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 5 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. {ECO:0000269|PubMed:15728307, ECO:0000269|PubMed:16814585, ECO:0000269|PubMed:17607606, ECO:0000269|PubMed:19309691, ECO:0000269|PubMed:20052765, ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:24038957, ECO:0000269|PubMed:24058541, ECO:0000269|PubMed:26342652, ECO:0000269|PubMed:9662406}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.166

Intolerance Scores

• loftool: 0.287
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.74

Haploinsufficiency Scores

• pHI: 0.0943
• hipred: N
• hipred_score: 0.150
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.386

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cln5
• 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

Gene ontology

• Biological process: signal peptide processing;lysosomal lumen acidification;brain development;neurogenesis;protein catabolic process;retrograde transport, endosome to Golgi;neuron maturation;glycosylation;positive regulation of GTP binding
• Cellular component: lysosome;lysosomal membrane;endoplasmic reticulum;Golgi apparatus;cytosol;integral component of membrane;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: protein binding;mannose binding