DNAJC6

DnaJ heat shock protein family (Hsp40) member C6, the group of C2 tensin-type domain containing|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 1:65248218-65415871

Links

ENSG00000116675 ∙ NCBI:9829 ∙ OMIM:608375 ∙ HGNC:15469 ∙ Uniprot:O75061 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• juvenile onset Parkinson disease 19A (Strong), mode of inheritance: AR
• juvenile onset Parkinson disease 19A (Limited), mode of inheritance: AR
• juvenile onset Parkinson disease 19A (Strong), mode of inheritance: AR
• juvenile onset Parkinson disease 19A (Moderate), mode of inheritance: AR
• young-onset Parkinson disease (Supportive), mode of inheritance: AR
• atypical juvenile parkinsonism (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 19A, juvenile-onset	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	Neurologic	22563501; 23211418

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC6 gene.

• Juvenile onset Parkinson disease 19A (179 variants)
• not provided (94 variants)
• Inborn genetic diseases (42 variants)
• not specified (7 variants)
• Malignant tumor of prostate (1 variants)
• Parkinson disease 19B, early-onset (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC6 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			1	45	10	56
missense			109	6	2	117
nonsense	2					2
start loss						0
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			8	3	1	12
non coding			1	44	35	80
Total	4	2	111	95	47

Variants in DNAJC6

This is a list of pathogenic ClinVar variants found in the DNAJC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-65264541-G-C			Benign (Jul 05, 2018)
1-65265168-C-T			Benign (Jul 05, 2018)
1-65265179-A-G			Benign (Jul 05, 2018)
1-65309229-C-T			Benign (Aug 30, 2018)
1-65309504-G-C			Benign (Jul 05, 2018)
1-65309638-G-A			Likely benign (Oct 14, 2018)
1-65309777-C-T		Juvenile onset Parkinson disease 19A	Uncertain significance (Jun 19, 2021)
1-65309824-G-T		Juvenile onset Parkinson disease 19A	Uncertain significance (Jul 10, 2023)
1-65309828-T-C		Juvenile onset Parkinson disease 19A	Uncertain significance (Apr 23, 2022)
1-65309846-G-C		Juvenile onset Parkinson disease 19A	Uncertain significance (Sep 24, 2020)
1-65309862-G-A		Juvenile onset Parkinson disease 19A	Likely benign (May 19, 2022)
1-65309864-G-T		Juvenile onset Parkinson disease 19A	Uncertain significance (Nov 08, 2021)
1-65309873-C-T		Juvenile onset Parkinson disease 19A	Uncertain significance (Feb 19, 2022)
1-65309889-G-T		Juvenile onset Parkinson disease 19A	Likely benign (Aug 14, 2023)
1-65309894-C-T		Juvenile onset Parkinson disease 19A	Uncertain significance (Jan 17, 2022)
1-65309899-C-G		Juvenile onset Parkinson disease 19A	Uncertain significance (Jan 09, 2024)
1-65309901-A-G		Juvenile onset Parkinson disease 19A	Likely benign (Mar 06, 2023)
1-65309909-C-A		Juvenile onset Parkinson disease 19A	Uncertain significance (Mar 30, 2022)
1-65309915-G-T		Juvenile onset Parkinson disease 19A	Uncertain significance (Oct 19, 2019)
1-65309920-A-G		Juvenile onset Parkinson disease 19A	Uncertain significance (Jul 23, 2018)
1-65309931-C-T		Juvenile onset Parkinson disease 19A	Likely benign (Jun 09, 2023)
1-65310115-G-A			Benign (Aug 17, 2018)
1-65310134-C-T			Benign (Sep 30, 2018)
1-65310159-C-T			Likely benign (Dec 24, 2018)
1-65364610-G-GT			Likely benign (Aug 20, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC6	protein_coding	protein_coding	ENST00000371069	19	167651

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000142	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	424	527	0.804	0.0000269	6327
Missense in Polyphen		157	234.48	0.66956		2857
Synonymous	0.626	186	197	0.943	0.0000107	1916
Loss of Function	5.70	5	47.3	0.106	0.00000233	560

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000196	0.000190
Ashkenazi Jewish	0.00	0.00
East Asian	0.000286	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000373	0.0000352
Middle Eastern	0.000286	0.000163
South Asian	0.000107	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recruits HSPA8/HSC70 to clathrin-coated vesicles and promotes uncoating of clathrin-coated vesicles. Plays a role in clathrin-mediated endocytosis in neurons (By similarity). {ECO:0000250|UniProtKB:Q80TZ3}.
• Disease: DISEASE: Parkinson disease 19B, early-onset (PARK19B) [MIM:615528]: An early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK19B is characterized by symptoms onset in the third-to-fifth decade, slow disease progression, and prominent. response to dopaminergic therapies. Inheritance is autosomal recessive. {ECO:0000269|PubMed:26528954}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human);Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.0587
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.07

Haploinsufficiency Scores

• pHI: 0.585
• hipred: Y
• hipred_score: 0.851
• ghis: 0.588

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.726

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc6
• Phenotype: growth/size/body region 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); reproductive system 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)

Gene ontology

• Biological process: receptor-mediated endocytosis;synaptic vesicle uncoating;peptidyl-tyrosine dephosphorylation;membrane organization;clathrin coat disassembly;clathrin-dependent endocytosis;regulation of clathrin-dependent endocytosis
• Cellular component: cytoplasm;cytosol;postsynaptic density;vesicle;intracellular membrane-bounded organelle;presynapse
• Molecular function: protein tyrosine phosphatase activity;SH3 domain binding;clathrin binding