DNAJB2

DnaJ heat shock protein family (Hsp40) member B2, the group of DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 2:219279341-219286898

Previous symbols: [ "HSJ1" ]

Links

ENSG00000135924 ∙ NCBI:3300 ∙ OMIM:604139 ∙ HGNC:5228 ∙ Uniprot:P25686 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, autosomal recessive 5 (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2T (Supportive), mode of inheritance: AR
• neuronopathy, distal hereditary motor, autosomal recessive 5 (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2T (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal recessive 5; Charcot-Marie-Tooth disease, axonal, type 2T	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	22522442; 24627108; 25274842

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJB2 gene.

• Neuronopathy, distal hereditary motor, autosomal recessive 5 (211 variants)
• not provided (51 variants)
• Inborn genetic diseases (33 variants)
• Charcot-Marie-Tooth disease (24 variants)
• not specified (16 variants)
• Autosomal recessive distal spinal muscular atrophy 2 (3 variants)
• DNAJB2-related condition (2 variants)
• Charcot-Marie-Tooth disease X-linked dominant 1 (1 variants)
• Charcot-Marie-Tooth disease axonal type 2T (1 variants)
• Neuronopathy, distal hereditary motor, autosomal recessive 5;Charcot-Marie-Tooth disease type 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJB2 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			4	43		47
missense		2	107	5	1	115
nonsense	4					4
start loss						0
frameshift	1	1				2
inframe indel			3			3
splice donor/acceptor (+/-2bp)	4	6	1			11
splice region			4	11	2	17
non coding			2	50	14	66
Total	9	9	117	98	15

Highest pathogenic variant AF is 0.0000197

Variants in DNAJB2

This is a list of pathogenic ClinVar variants found in the DNAJB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-219279528-G-C		not specified	Likely benign (Oct 19, 2017)
2-219279538-T-G		not specified	Benign (Jun 22, 2016)
2-219279593-C-T			Likely benign (Jul 28, 2018)
2-219279688-G-C		Neuronopathy, distal hereditary motor, autosomal recessive 5	Benign (Jul 30, 2021)
2-219279706-T-C			Likely benign (Jul 28, 2018)
2-219279787-C-G		not specified	Likely benign (Jul 12, 2017)
2-219279799-C-G		not specified	Likely benign (Jul 25, 2017)
2-219279800-C-A			Benign (Mar 03, 2015)
2-219279811-C-T		not specified	Likely benign (Oct 20, 2016)
2-219279837-G-A		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Jun 20, 2022)
2-219279847-A-G		Neuronopathy, distal hereditary motor, autosomal recessive 5 • Charcot-Marie-Tooth disease • Autosomal recessive distal spinal muscular atrophy 2	Likely pathogenic (Mar 31, 2020)
2-219279850-A-G		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Aug 13, 2021)
2-219279854-C-A		Neuronopathy, distal hereditary motor, autosomal recessive 5	Likely benign (Oct 01, 2022)
2-219279860-C-T		Neuronopathy, distal hereditary motor, autosomal recessive 5	Likely benign (Aug 20, 2020)
2-219279866-G-T		Neuronopathy, distal hereditary motor, autosomal recessive 5	Likely benign (May 22, 2023)
2-219279874-C-T		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Jul 26, 2021)
2-219279876-T-C		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Nov 26, 2019)
2-219279896-G-A		Neuronopathy, distal hereditary motor, autosomal recessive 5	Likely benign (Apr 05, 2021)
2-219279897-G-C		Inborn genetic diseases	Uncertain significance (Aug 24, 2021)
2-219279898-C-A		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Sep 25, 2019)
2-219279899-G-A		Neuronopathy, distal hereditary motor, autosomal recessive 5	Likely pathogenic (Sep 01, 2021)
2-219279903-G-T		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Apr 26, 2022)
2-219279908-T-G		Neuronopathy, distal hereditary motor, autosomal recessive 5	Likely benign (Apr 14, 2023)
2-219279910-C-T		Neuronopathy, distal hereditary motor, autosomal recessive 5	Uncertain significance (Jun 10, 2023)
2-219279913-A-T		Neuronopathy, distal hereditary motor, autosomal recessive 5	Benign (Oct 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJB2	protein_coding	protein_coding	ENST00000336576	8	7634

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000544	0.891	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.721	174	203	0.857	0.0000128	2078
Missense in Polyphen		64	75.696	0.84548		796
Synonymous	-0.0547	77	76.4	1.01	0.00000411	673
Loss of Function	1.49	9	15.3	0.589	7.43e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000581	0.000581
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00	0.00
Finnish	0.000143	0.000139
European (Non-Finnish)	0.000195	0.000193
Middle Eastern	0.00	0.00
South Asian	0.000103	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:7957263, PubMed:22219199). In parallel, also contributes to the ubiquitin- dependent proteasomal degradation of misfolded proteins (PubMed:15936278, PubMed:21625540). Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes (PubMed:12754272, PubMed:20889486, PubMed:21719532, PubMed:22396390, PubMed:24023695). Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins (PubMed:15936278). {ECO:0000269|PubMed:12754272, ECO:0000269|PubMed:15936278, ECO:0000269|PubMed:20889486, ECO:0000269|PubMed:21625540, ECO:0000269|PubMed:21719532, ECO:0000269|PubMed:22219199, ECO:0000269|PubMed:22396390, ECO:0000269|PubMed:24023695, ECO:0000269|PubMed:7957263}.
• Disease: DISEASE: Distal spinal muscular atrophy, autosomal recessive, 5 (DSMA5) [MIM:614881]: An autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired. {ECO:0000269|PubMed:22522442, ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:25274842}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0835

Intolerance Scores

• loftool: 0.818
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.171
• hipred: N
• hipred_score: 0.381
• ghis: 0.501

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajb2

Gene ontology

• Biological process: response to unfolded protein;negative regulation of cell population proliferation;negative regulation of cell growth;ubiquitin-dependent ERAD pathway;regulation of protein ubiquitination;negative regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of ATPase activity;protein refolding;chaperone-mediated protein folding;neuron cellular homeostasis;negative regulation of inclusion body assembly;regulation of chaperone-mediated protein folding
• Cellular component: proteasome complex;nucleus;cytosol;intrinsic component of endoplasmic reticulum membrane;nuclear membrane
• Molecular function: ATPase activator activity;protein binding;Hsp70 protein binding;ubiquitin binding;unfolded protein binding;chaperone binding;ubiquitin-dependent protein binding