DNAJC19

DnaJ heat shock protein family (Hsp40) member C19, the group of TIM23 complex|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 3:180983696-180989774

Links

ENSG00000205981 ∙ NCBI:131118 ∙ OMIM:608977 ∙ HGNC:30528 ∙ Uniprot:Q96DA6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylglutaconic aciduria type 5 (Strong), mode of inheritance: AR
• 3-methylglutaconic aciduria type 5 (Supportive), mode of inheritance: AR
• 3-methylglutaconic aciduria type 5 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-methylglutaconic aciduria, type V	AR	Cardiovascular	Individuals frequently demonstrate findings including cardiac manifestations such as dilated cardiomyopathy and dysrhythmias, and surveillance may allow early detection and management	Biochemical; Cardiovascular; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Ophthalmologic	16055927; 22981120

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC19 gene.

• 3-methylglutaconic aciduria type 5 (92 variants)
• not provided (27 variants)
• not specified (10 variants)
• Inborn genetic diseases (4 variants)
• 3-Methylglutaconic aciduria type 3 (1 variants)
• DNAJC19-related condition (1 variants)
• 3-Methylglutaconic aciduria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC19 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				13		13
missense			32			32
nonsense	3					3
start loss			2			2
frameshift	1	2	3			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3	1	1		6
splice region			4	5	1	10
non coding			4	22	9	35
Total	5	5	43	36	9

Highest pathogenic variant AF is 0.0000460

Variants in DNAJC19

This is a list of pathogenic ClinVar variants found in the DNAJC19 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-180984096-T-TAC		3-methylglutaconic aciduria type 5	Uncertain significance (Jun 14, 2016)
3-180984152-C-G		3-methylglutaconic aciduria type 5	Uncertain significance (Jun 14, 2016)
3-180984442-ATAAT-A		3-methylglutaconic aciduria type 5	Uncertain significance (Jun 14, 2016)
3-180984452-C-T			Benign (Jun 23, 2018)
3-180984642-AT-A		3-methylglutaconic aciduria type 5	Uncertain significance (Aug 15, 2022)
3-180984643-T-C		3-methylglutaconic aciduria type 5	Likely benign (Nov 07, 2021)
3-180984647-T-C		3-methylglutaconic aciduria type 5	Uncertain significance (Oct 03, 2022)
3-180984658-T-C		3-methylglutaconic aciduria type 5	Likely benign (Feb 11, 2023)
3-180984659-T-G		3-methylglutaconic aciduria type 5	Uncertain significance (Jul 11, 2022)
3-180984660-C-G		3-methylglutaconic aciduria type 5 • not specified	Conflicting classifications of pathogenicity (Dec 11, 2023)
3-180984660-C-T		3-methylglutaconic aciduria type 5	Uncertain significance (Jan 23, 2022)
3-180984665-A-G		3-methylglutaconic aciduria type 5	Uncertain significance (Jul 17, 2022)
3-180984666-A-C		3-methylglutaconic aciduria type 5	Uncertain significance (Jun 11, 2021)
3-180984675-C-T		3-methylglutaconic aciduria type 5	Uncertain significance (Apr 24, 2022)
3-180984690-CT-C		3-methylglutaconic aciduria type 5	Pathogenic (Oct 01, 2012)
3-180984691-T-C		3-methylglutaconic aciduria type 5	Likely benign (Jan 12, 2024)
3-180984695-A-AT		3-methylglutaconic aciduria type 5	Uncertain significance (Dec 11, 2023)
3-180984696-T-C		3-methylglutaconic aciduria type 5	Uncertain significance (Mar 11, 2022)
3-180984697-A-G		3-methylglutaconic aciduria type 5	Likely benign (Jan 31, 2023)
3-180984698-T-TA			Likely pathogenic (Jan 01, 2021)
3-180984703-A-C		3-methylglutaconic aciduria type 5	Likely benign (Aug 07, 2021)
3-180984706-T-G		not specified • 3-methylglutaconic aciduria type 5	Benign/Likely benign (Mar 01, 2024)
3-180984710-C-A			Uncertain significance (Feb 12, 2021)
3-180984712-T-G		3-methylglutaconic aciduria type 5	Likely pathogenic (Mar 17, 2024)
3-180984714-T-A		DNAJC19-related disorder	Likely benign (Jun 10, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC19	protein_coding	protein_coding	ENST00000382564	6	6066

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000613	0.741	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.876	44	63.7	0.691	0.00000336	747
Missense in Polyphen		8	14.931	0.5358		197
Synonymous	0.152	18	18.8	0.955	9.07e-7	216
Loss of Function	0.934	6	9.03	0.664	5.47e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000570	0.000570
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000976	0.000971
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity). {ECO:0000250}.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.672
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.247
• hipred: Y
• hipred_score: 0.788
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc19
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: protein folding;protein targeting to mitochondrion;visual perception;protein import into mitochondrial matrix;positive regulation of ATPase activity;genitalia development
• Cellular component: PAM complex, Tim23 associated import motor;mitochondrion;mitochondrial inner membrane;integral component of membrane;protein-containing complex
• Molecular function: ATPase activator activity;protein binding;protein transporter activity