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
Phenotypes
GenCC
Source:
- 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:
| 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
- Inborn_genetic_diseases (43 variants)
- not_provided (22 variants)
- Juvenile-onset_diabetes_mellitus-central_and_peripheral_neurodegeneration_syndrome (11 variants)
- DNAJC3-related_disorder (9 variants)
- not_specified (5 variants)
- Prostate_cancer (1 variants)
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. These statistics are base on transcript: NM_000006260.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 12 | ||||
| missense | 48 | 50 | ||||
| nonsense | 4 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 5 | 6 | 49 | 13 | 1 |
Highest pathogenic variant AF is 0.000011180041
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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