DNAJC13

DnaJ heat shock protein family (Hsp40) member C13, the group of Armadillo like helical domain containing|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 3:132417502-132539032

Links

ENSG00000138246 ∙ NCBI:23317 ∙ OMIM:614334 ∙ HGNC:30343 ∙ Uniprot:O75165 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary late onset Parkinson disease (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 21	AD	Neurologic	Response to levodopa has been described	Neurologic	24218364; 25186792

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC13 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC13 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	16	6	23
missense			98	11	10	119
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	8	11
non coding				2	103	105
Total	0	0	99	29	119

Variants in DNAJC13

This is a list of pathogenic ClinVar variants found in the DNAJC13 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-132434209-C-CA			Benign (Oct 05, 2019)
3-132434272-G-C			Benign (Jul 10, 2018)
3-132434289-C-G			Benign (Jul 09, 2018)
3-132434331-AGCAAAGATCGTGC-A			Benign (Jul 14, 2018)
3-132434384-C-CA			Benign (Oct 07, 2019)
3-132434489-T-TAG			Benign (Jul 09, 2018)
3-132434570-A-G		not specified	Uncertain significance (May 27, 2022)
3-132434768-A-G			Benign (Jul 09, 2018)
3-132446211-T-A			Benign (Jul 09, 2018)
3-132446334-A-T			Benign (Jul 09, 2018)
3-132446504-A-G		DNAJC13-related disorder	Uncertain significance (Apr 29, 2023)
3-132446505-T-A		not specified	Uncertain significance (Dec 01, 2022)
3-132446507-C-T		not specified	Uncertain significance (Feb 10, 2022)
3-132446514-T-C			Likely benign (Jun 15, 2018)
3-132446756-AG-A			Benign (Jul 14, 2018)
3-132447161-A-G			Benign (Jul 09, 2018)
3-132447328-A-G		not specified	Uncertain significance (Nov 21, 2022)
3-132447336-A-G		not specified	Uncertain significance (Jun 06, 2023)
3-132447373-C-T		DNAJC13-related disorder	Uncertain significance (Feb 20, 2023)
3-132447393-C-G		not specified	Uncertain significance (Sep 15, 2021)
3-132447393-C-T		not specified	Uncertain significance (Dec 13, 2021)
3-132447422-T-G		not specified	Benign (Jul 05, 2018)
3-132447435-A-G		not specified	Uncertain significance (Feb 21, 2024)
3-132447458-T-G		not specified • DNAJC13-related disorder	Likely benign (-)
3-132447465-G-A		not specified	Uncertain significance (Sep 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC13	protein_coding	protein_coding	ENST00000260818	55	121507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.49e-9	125721	0	26	125747	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	945	1.16e+3	0.812	0.0000591	14770
Missense in Polyphen		142	251.79	0.56396		3274
Synonymous	0.722	383	401	0.954	0.0000206	4150
Loss of Function	9.16	17	129	0.131	0.00000688	1625

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000427	0.000424
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000897	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.0000374	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in membrane trafficking through early endosomes, such as the early endosome to recycling endosome transport implicated in the recycling of transferrin and the early endosome to late endosome transport implicated in degradation of EGF and EGFR (PubMed:18256511, PubMed:18307993). Involved in the regulation of endosomal membrane tubulation and regulates th dynamics of SNX1 on the endosomal membrane; via association with WASHC2 may link the WASH complex to the retromer SNX-BAR subcomplex (PubMed:24643499). {ECO:0000269|PubMed:18256511, ECO:0000269|PubMed:18307993, ECO:0000269|PubMed:24643499}.
• Disease: DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease 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. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. {ECO:0000269|PubMed:24218364, ECO:0000269|PubMed:25393719}. Note=The gene represented in this entry may be involved in disease pathogenesis. Genetic variants in DNAJC13 (PubMed:24218364, PubMed:25393719) and TMEM230 (PubMed:27270108) have been found in the same large multigenerational family with adult-onset Parkinson disease. The pathological role of each gene and therefore the exact molecular basis of the disease is unclear. {ECO:0000305|PubMed:27270108}.
• Pathway: Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.372
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.77

Haploinsufficiency Scores

• pHI: 0.418
• hipred: N
• hipred_score: 0.476
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc13

Gene ontology

• Biological process: osteoblast differentiation;receptor-mediated endocytosis;endosome organization;protein transport;neutrophil degranulation;regulation of early endosome to recycling endosome transport;regulation of early endosome to late endosome transport
• Cellular component: lysosomal membrane;cytosol;plasma membrane;endosome membrane;membrane;secretory granule membrane;early endosome membrane;azurophil granule membrane;intracellular membrane-bounded organelle;extracellular exosome;WASH complex
• Molecular function: protein binding