DNAJC5

DnaJ heat shock protein family (Hsp40) member C5, the group of MicroRNA protein coding host genes|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 20:63895125-63936031

Previous symbols: [ "CLN4" ]

Links

ENSG00000101152 ∙ NCBI:80331 ∙ OMIM:611203 ∙ HGNC:16235 ∙ Uniprot:Q9H3Z4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ceroid lipofuscinosis, neuronal, 4 (Kufs type) (Strong), mode of inheritance: AD
• ceroid lipofuscinosis, neuronal, 4 (Kufs type) (Strong), mode of inheritance: AD
• ceroid lipofuscinosis, neuronal, 4 (Kufs type) (Supportive), mode of inheritance: AD
• adult neuronal ceroid lipofuscinosis (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant	AD	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	5132971; 4414475; 62240; 932739; 11489285; 12112194; 21820099; 22073189; 22235333; 22978711

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC5 gene.

• Neuronal ceroid lipofuscinosis (175 variants)
• Ceroid lipofuscinosis, neuronal, 4 (Kufs type) (153 variants)
• Neuronal Ceroid-Lipofuscinosis, Recessive (110 variants)
• not provided (91 variants)
• not specified (35 variants)
• Inborn genetic diseases (19 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC5 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				72	2	74
missense	2		66	3		71
nonsense			1			1
start loss						0
frameshift						0
inframe indel	2		1			3
splice donor/acceptor (+/-2bp)			3		1	4
splice region			5	9		14
non coding			77	87	24	188
Total	4	0	148	162	27

Variants in DNAJC5

This is a list of pathogenic ClinVar variants found in the DNAJC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-63895141-C-T		Neuronal Ceroid-Lipofuscinosis, Recessive • Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 13, 2018)
20-63895147-T-TCCGCTG		Neuronal Ceroid-Lipofuscinosis, Recessive	Likely benign (Jun 14, 2016)
20-63895149-C-T		Neuronal Ceroid-Lipofuscinosis, Recessive • Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 13, 2018)
20-63895150-G-T		Neuronal Ceroid-Lipofuscinosis, Recessive • Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 13, 2018)
20-63895169-C-CTGCCGG		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
20-63895175-G-C		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
20-63895194-T-TGCC		Neuronal Ceroid-Lipofuscinosis, Recessive	Benign (May 29, 2020)
20-63895194-T-TGCCGCC		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
20-63895194-T-TGCCGCCGCC			Benign (Jun 01, 2022)
20-63895226-A-G		Neuronal Ceroid-Lipofuscinosis, Recessive • Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 12, 2018)
20-63895240-G-C		Neuronal Ceroid-Lipofuscinosis, Recessive • Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 12, 2018)
20-63895246-C-G		Neuronal Ceroid-Lipofuscinosis, Recessive • Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 12, 2018)
20-63895274-A-AGCGGAGCC		not specified	Likely benign (Dec 05, 2017)
20-63895290-C-G		not specified	Likely benign (Mar 11, 2016)
20-63895297-A-AGGGC		not specified	Likely benign (Jun 09, 2017)
20-63895302-G-A		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
20-63895308-GCGGGCGGA-G		not specified	Likely benign (Mar 09, 2016)
20-63895322-AGGTGAGCTCGCTGCGGGTCGGGCGGGCG-A			Uncertain significance (Sep 23, 2020)
20-63895334-T-A		Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 12, 2018)
20-63895335-G-T		not specified	Likely benign (Mar 02, 2016)
20-63895338-G-T		Ceroid lipofuscinosis, neuronal, 4 (Kufs type)	Uncertain significance (Jan 13, 2018)
20-63895343-G-A		not specified	Benign (Feb 05, 2016)
20-63895366-G-A			Benign (Sep 24, 2019)
20-63895448-G-C			Likely benign (Jun 28, 2018)
20-63928326-T-C		not specified	Likely benign (May 16, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC5	protein_coding	protein_coding	ENST00000360864	4	40867

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.812	0.187	125279	0	1	125280	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.79	66	122	0.543	0.00000864	1292
Missense in Polyphen		10	37.796	0.26458		428
Synonymous	-1.12	70	59.0	1.19	0.00000574	361
Loss of Function	2.62	1	9.89	0.101	4.32e-7	119

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000617
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a general chaperone in regulated exocytosis (By similarity). Acts as a co-chaperone for the SNARE protein SNAP-25 (By similarity). Involved in the calcium-mediated control of a late stage of exocytosis (By similarity). May have an important role in presynaptic function. May be involved in calcium-dependent neurotransmitter release at nerve endings (By similarity). {ECO:0000250|UniProtKB:P60904, ECO:0000250|UniProtKB:Q29455}.
• Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 4B (CLN4B) [MIM:162350]: 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. CLN4B has no visual involvement and is characterized by seizures and other neurologic symptoms. {ECO:0000269|PubMed:21820099, ECO:0000269|PubMed:22073189, ECO:0000269|PubMed:22235333, ECO:0000269|PubMed:22902780, ECO:0000269|PubMed:22978711}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Neutrophil degranulation;Innate Immune System;Immune System;Neuronal System;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.179
• hipred: Y
• hipred_score: 0.765
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc5
• Phenotype: hearing/vestibular/ear 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; 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); muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: exocytosis;synaptic vesicle exocytosis;neutrophil degranulation;negative regulation of neuron apoptotic process;regulated exocytosis;chaperone-mediated protein folding;regulation of synaptic vesicle cycle
• Cellular component: mitochondrion;lysosomal membrane;plasma membrane;membrane;neuromuscular junction;azurophil granule membrane;specific granule membrane;melanosome;clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane;anchored component of synaptic vesicle membrane
• Molecular function: protein binding;ATP-dependent protein binding