DNAJC3

DnaJ heat shock protein family (Hsp40) member C3, the group of Tetratricopeptide repeat domain containing|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 13:95677139-95794988

Previous symbols: [ "PRKRI" ]

Links

ENSG00000102580 ∙ NCBI:5611 ∙ OMIM:601184 ∙ HGNC:9439 ∙ Uniprot:Q13217 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Strong), mode of inheritance: AR
• juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Strong), mode of inheritance: AR
• juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Moderate), mode of inheritance: AR
• juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Supportive), mode of inheritance: AR
• type 2 diabetes mellitus (Limited), mode of inheritance: AD
• juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus	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	Audiologic/Otolaryngologic; Endocrine; Neurologic	25466870

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC3 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				10	1	11
missense			20	2		22
nonsense		1				1
start loss						0
frameshift		2				2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				3		3
non coding				1	1	2
Total	0	3	21	13	2

Variants in DNAJC3

This is a list of pathogenic ClinVar variants found in the DNAJC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-95677256-A-G		Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	Pathogenic (Jun 23, 2022)
13-95677315-C-T			Likely benign (Dec 31, 2019)
13-95677316-C-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
13-95677333-C-T		DNAJC3-related disorder	Benign (Dec 31, 2019)
13-95709217-T-C			Likely benign (Jul 13, 2018)
13-95709255-T-A		DNAJC3-related disorder	Likely benign (Jul 21, 2019)
13-95709281-A-G		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
13-95709306-T-G		DNAJC3-related disorder	Benign/Likely benign (Feb 01, 2023)
13-95723254-A-G		not specified	Uncertain significance (May 04, 2022)
13-95723345-A-G		DNAJC3-related disorder	Likely benign (Dec 31, 2019)
13-95725236-A-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
13-95725254-T-C		Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	Pathogenic (Jun 23, 2022)
13-95725254-T-G		Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	Pathogenic (Jun 23, 2022)
13-95757644-C-T		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
13-95757670-A-C		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
13-95757706-T-C			Likely benign (Nov 09, 2018)
13-95760073-C-T		Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome • Malignant tumor of prostate	Conflicting classifications of pathogenicity (Dec 04, 2014)
13-95760146-A-C		Inborn genetic diseases	Uncertain significance (Jul 20, 2022)
13-95760164-C-G		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
13-95760212-T-C		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
13-95760676-C-T		DNAJC3-related disorder	Likely benign (Nov 19, 2019)
13-95760678-G-A		Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	Uncertain significance (Sep 11, 2023)
13-95760679-T-C		Inborn genetic diseases	Likely benign (Nov 27, 2023)
13-95760699-A-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
13-95760758-A-C			Uncertain significance (Nov 06, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC3	protein_coding	protein_coding	ENST00000602402	12	117851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0175	0.982	125719	0	20	125739	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	186	264	0.703	0.0000136	3321
Missense in Polyphen		45	94.63	0.47554		1194
Synonymous	0.844	85	95.5	0.890	0.00000515	886
Loss of Function	3.60	9	30.5	0.295	0.00000167	378

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000146	0.000146
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.0000581	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000890	0.0000879
Middle Eastern	0.0000581	0.0000544
South Asian	0.00	0.00
Other	0.000505	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Acts as a negative regulator of the EIF2AK4/GCN2 kinase activity by preventing the phosphorylation of eIF-2-alpha at 'Ser-52' and hence attenuating general protein synthesis under ER stress, hypothermic and amino acid starving stress conditions (By similarity). Co-chaperone of HSPA8/HSC70, it stimulates its ATPase activity. May inhibit both the autophosphorylation of EIF2AK2/PKR and the ability of EIF2AK2 to catalyze phosphorylation of the EIF2A. May inhibit EIF2AK3/PERK activity. {ECO:0000250|UniProtKB:Q27968, ECO:0000250|UniProtKB:Q91YW3, ECO:0000269|PubMed:12601012, ECO:0000269|PubMed:8576172, ECO:0000269|PubMed:9447982, ECO:0000269|PubMed:9920933}.
• Disease: DISEASE: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus (ACPHD) [MIM:616192]: A disease characterized by juvenile-onset diabetes and neurodegeneration, resulting in ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. {ECO:0000269|PubMed:25466870}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Influenza A - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);XBP1(S) activates chaperone genes;Photodynamic therapy-induced unfolded protein response;double stranded rna induced gene expression;Neutrophil degranulation;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.526
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.25

Haploinsufficiency Scores

• pHI: 0.174
• hipred: Y
• hipred_score: 0.775
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.310

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc3
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; hematopoietic 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); immune system phenotype; renal/urinary system phenotype; digestive/alimentary 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: negative regulation of protein kinase activity;protein folding in endoplasmic reticulum;positive regulation of translation initiation in response to endoplasmic reticulum stress;IRE1-mediated unfolded protein response;negative regulation of apoptotic process;neutrophil degranulation;post-translational protein modification;cellular protein metabolic process;proteolysis involved in cellular protein catabolic process;defense response to virus;cellular response to cold;negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation
• Cellular component: extracellular region;cytoplasm;endoplasmic reticulum;endoplasmic reticulum lumen;smooth endoplasmic reticulum;cytosol;membrane;azurophil granule lumen;extracellular exosome;extracellular vesicle
• Molecular function: protein kinase inhibitor activity;protein kinase binding;unfolded protein binding;chaperone binding;misfolded protein binding