DNAJB6

DnaJ heat shock protein family (Hsp40) member B6, the group of DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 7:157335381-157417439

Previous symbols: [ "LGMD1D" ]

Links

ENSG00000105993 ∙ NCBI:10049 ∙ OMIM:611332 ∙ HGNC:14888 ∙ Uniprot:O75190 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (Supportive), mode of inheritance: AD
• autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (Strong), mode of inheritance: AD
• muscular dystrophy, limb-girdle, autosomal dominant (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, limb-girdle, autosomal dominant 1	AD	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	Musculoskeletal	22334415; 22366786; 24594375; 26205529; 30055862

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJB6 gene.

• Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (9 variants)
• not provided (5 variants)
• Abnormality of the musculature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJB6 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				55	2	57
missense	9	2	137	7		155
nonsense			6			6
start loss						0
frameshift			5			5
inframe indel			6			6
splice donor/acceptor (+/-2bp)			3			3
splice region			3	9	1	13
non coding			36	69	38	143
Total	9	2	193	131	40

Highest pathogenic variant AF is 0.00000657

Variants in DNAJB6

This is a list of pathogenic ClinVar variants found in the DNAJB6 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-157337063-C-A		Myofibrillar Myopathy, Dominant • Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Jan 13, 2018)
7-157337078-G-T		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) • Limb-Girdle Muscular Dystrophy, Dominant	Uncertain significance (Jan 12, 2018)
7-157337085-G-A		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) • Myofibrillar Myopathy, Dominant	Benign/Likely benign (May 26, 2021)
7-157337086-G-T		Myofibrillar Myopathy, Dominant • Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Conflicting classifications of pathogenicity (Jan 12, 2018)
7-157337094-G-A		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Jan 13, 2018)
7-157337108-C-G		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Benign/Likely benign (Nov 21, 2021)
7-157337128-G-T		Myofibrillar Myopathy, Dominant • Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Benign/Likely benign (Jan 12, 2018)
7-157337288-C-T			Benign (Jul 03, 2018)
7-157337335-A-T			Benign (Jul 03, 2018)
7-157358329-C-T			Benign (Jun 14, 2018)
7-157358492-C-T			Likely benign (Sep 18, 2018)
7-157358540-C-T		not specified • Limb-Girdle Muscular Dystrophy, Dominant • Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Benign (Jul 30, 2021)
7-157358565-C-G			Uncertain significance (Sep 07, 2017)
7-157358565-C-T			Uncertain significance (Mar 04, 2016)
7-157358566-G-A		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Jan 13, 2018)
7-157358593-T-G		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Likely benign (Aug 30, 2021)
7-157358599-C-T		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Likely benign (Oct 05, 2022)
7-157358612-G-T		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Sep 01, 2023)
7-157358616-C-CA		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Mar 08, 2022)
7-157358620-C-A		DNAJB6-related disorder	Likely benign (Aug 14, 2024)
7-157358620-C-G		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Likely benign (Mar 10, 2022)
7-157358620-C-T		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) • not specified • DNAJB6-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
7-157358621-G-T		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Sep 17, 2022)
7-157358624-G-A		DNAJB6-related disorder • Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) • Inborn genetic diseases	Uncertain significance (Nov 20, 2024)
7-157358627-A-G		Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Uncertain significance (Jun 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJB6	protein_coding	protein_coding	ENST00000262177	9	82059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.854	0.146	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.17	148	194	0.763	0.0000122	2100
Missense in Polyphen		21	36.162	0.58071		403
Synonymous	-1.16	96	82.6	1.16	0.00000592	620
Loss of Function	3.46	3	19.5	0.154	0.00000124	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000332	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Isoform B but not isoform A inhibits huntingtin aggregation. Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. Also reduces cellular toxicity and caspase-3 activity. {ECO:0000269|PubMed:10954706, ECO:0000269|PubMed:11896048, ECO:0000269|PubMed:20159555, ECO:0000269|PubMed:22366786, ECO:0000269|PubMed:28233300}.
• Disease: DISEASE: Limb-girdle muscular dystrophy 1E (LGMD1E) [MIM:603511]: An autosomal dominant myopathy characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region. {ECO:0000269|PubMed:22334415, ECO:0000269|PubMed:22366786}. Note=The disease is caused by mutations affecting the gene represented in this entry. There is evidence that LGMD1E is caused by dysfunction of isoform B (PubMed:22366786). {ECO:0000269|PubMed:22366786}.
• Pathway: Cellular response to heat stress;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;prion pathway;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Recessive Scores

• pRec: 0.219

Intolerance Scores

• loftool: 0.477
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.342
• hipred: Y
• hipred_score: 0.633
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajb6
• Phenotype: embryo 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); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: dnajb6a
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: refractivity

Gene ontology

• Biological process: protein folding;actin cytoskeleton organization;extracellular matrix organization;positive regulation of ATPase activity;regulation of protein localization;protein localization to nucleus;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;intermediate filament organization;negative regulation of transcription, DNA-templated;chorio-allantoic fusion;syncytiotrophoblast cell differentiation involved in labyrinthine layer development;chorion development;negative regulation of inclusion body assembly;regulation of cellular response to heat
• Cellular component: nucleus;nucleoplasm;cytosol;membrane;Z disc;perinuclear region of cytoplasm
• Molecular function: ATPase activator activity;DNA binding;protein binding;heat shock protein binding;unfolded protein binding;chaperone binding