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DNAJB11
DnaJ heat shock protein family (Hsp40) member B11
The DNAJB11 gene encodes a heat shock protein that plays a crucial role in protein folding and stress responses within cells, with implications for various health conditions. The DNAJB11 gene, or DnaJ heat shock protein family (Hsp40) member B11, is vital for maintaining cellular health through its function as a co-chaperone.
DNAJB11 is located on the long (q) arm of chromosome 3, at band 3q27.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The DNAJB11 gene provides instructions for making a protein known as DnaJ heat shock protein family (Hsp40) member B11. This protein is a critical component of the cellular machinery responsible for maintaining protein homeostasis, also known as proteostasis.
As a co-chaperone, DNAJB11 works closely with other heat shock proteins, especially Hsp70, to ensure that newly synthesised proteins fold into their correct three-dimensional structures and that misfolded proteins are either refolded or targeted for degradation. This function is essential for normal cellular operation and for protecting cells from various stressors, including heat shock and oxidative stress. Variants in the DNAJB11 gene have been linked to a spectrum of health conditions, particularly those affecting kidney and liver development and function.
What the gene does
The DNAJB11 gene product, DnaJ heat shock protein family (Hsp40) member B11, primarily functions as a molecular co-chaperone in the endoplasmic reticulum (ER), a critical organelle within cells responsible for protein synthesis and folding. Within the ER lumen, DNAJB11 interacts with the main chaperone protein Hsp70 (also known as BiP or GRP78), stimulating its ATPase activity. This stimulatory action is crucial for Hsp70 to efficiently bind to unfolded or misfolded proteins, facilitate their proper folding, or direct them for degradation through ER-associated degradation (ERAD) pathways. This partnership is vital for protein quality control, ensuring that only correctly folded proteins are trafficked to their final destinations.
Beyond basic protein folding, DNAJB11 participates in the cellular stress response, helping cells cope with conditions that lead to an accumulation of misfolded proteins, such as oxidative stress or nutrient deprivation. Maintaining protein homeostasis is fundamental for cell survival and proper organ function. Disruption of DNAJB11's function can therefore lead to an accumulation of misfolded proteins, triggering ER stress and potentially contributing to cellular dysfunction and disease, particularly in organs with high protein synthesis and folding demands like the kidneys and liver.
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Chromosome location
The DNAJB11 gene is situated on chromosome 3, specifically at position 3q27.3. Chromosome 3 is one of the 23 pairs of chromosomes in humans, containing hundreds of genes that provide instructions for various cellular processes. The 'q' arm denotes the long arm of the chromosome, and '27.3' refers to the specific band location within that arm. This precise genomic address helps scientists locate and study the gene, understand its organisation within the human genome, and investigate its involvement in health and disease.
Protein structure
The DNAJB11 protein is composed of 358 amino acids. A key functional region of this protein is the J (Domain), spanning from amino acids 25 to 90. This J domain is characteristic of DnaJ/Hsp40 family proteins and is essential for its co-chaperone activity. It typically contains a conserved HPD (histidine-proline-aspartate) motif, which is crucial for interacting with and stimulating the ATPase activity of Hsp70 chaperones. This interaction is fundamental for the protein's role in assisting protein folding and quality control within the cell.
Key variants
Genetic variations, or variants, in the DNAJB11 gene can lead to changes in the structure or function of the DnaJ heat shock protein family (Hsp40) member B11. These variants can either reduce the protein's ability to assist in protein folding and quality control or disrupt its interactions with other cellular components. Depending on the nature and location of the variant, its impact can range from mild alterations in protein function to complete loss of function, potentially leading to the development or progression of associated conditions. The inheritance pattern for conditions linked to DNAJB11 variants can be autosomal recessive or autosomal dominant.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.100C>T | p.Arg34Ter | Pathogenic | ★★☆☆ | Autosomal dominant polycystic kidney disease |
c.400del | p.Ile134fs | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal dominant polycystic kidney disease |
c.430G>T | p.Glu144Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal dominant polycystic kidney disease |
c.616C>T | p.Arg206Ter | Pathogenic | ★★☆☆ | Polycystic kidney disease 6 with or without polycystic liver disease |
c.70C>T | p.Arg24Ter | Pathogenic | ★★☆☆ | Polycystic kidney disease |
c.724C>T | p.Arg242Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.70_85del | - | Pathogenic | ★☆☆☆ | Autosomal dominant polycystic kidney disease |
c.151C>T | p.Gln51Ter | Pathogenic | ★☆☆☆ | Polycystic kidney disease 6 with or without polycystic liver disease |
c.258C>G | p.Tyr86Ter | Pathogenic | ★☆☆☆ | Polycystic kidney disease 6 with or without polycystic liver disease |
c.425T>A | p.Leu142Ter | Pathogenic | ★☆☆☆ | Autosomal dominant polycystic kidney disease |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the DNAJB11 gene have been associated with a range of conditions, primarily affecting the kidneys and liver. These conditions include cystic kidney disease, which involves the formation of fluid-filled sacs in the kidneys, and ductal plate malformation, an abnormality in the development of bile ducts in the liver. Furthermore, DNAJB11 variants can contribute to foetal anomalies, which are structural or functional abnormalities that occur during prenatal development. Polycystic liver disease, characterised by multiple cysts in the liver, and tubulointerstitial kidney disease, affecting the tubules and interstitium of the kidneys, are also recognised as potentially linked to DNAJB11.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic DNAJB11 variants typically follow ar/ad inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
Within the UK, the clinical relevance of the DNAJB11 gene is recognised by its inclusion in several NHS Genomic Medicine Service national test panels. It is listed as 'green' for cystic kidney disease, ductal plate malformation, foetal anomalies, polycystic liver disease (R173), and tubulointerstitial kidney disease (R202). A 'green' status indicates that there is sufficient evidence for a strong association between variants in the DNAJB11 gene and these conditions, making it suitable for diagnostic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
General lifestyle considerations for individuals concerned about conditions associated with the DNAJB11 gene typically focus on maintaining overall health, particularly kidney and liver function. Research suggests that a balanced diet, adequate hydration, and regular physical activity can support organ health in the general population. Avoiding excessive alcohol consumption and certain medications that can strain the liver or kidneys may also be beneficial. Smoking cessation is generally recommended for its broad health benefits. These are general health recommendations and individual dietary or lifestyle modifications should always be discussed with a healthcare professional.
Supplement considerations
There is no conclusive evidence that specific dietary supplements can prevent or treat conditions associated with variants in the DNAJB11 gene. For the general population, maintaining a balanced diet typically provides all necessary vitamins and minerals. If considering any supplements, particularly those marketed for kidney or liver health, it is essential to consult a healthcare provider. Some supplements can interact with medications or have adverse effects, especially for individuals with pre-existing health conditions.
Frequently asked questions
What is the DNAJB11 gene?
The DNAJB11 gene provides instructions for making a protein that functions as a co-chaperone. It helps other proteins fold correctly and assists in maintaining cellular protein quality control, particularly in the endoplasmic reticulum.
What conditions are associated with DNAJB11 variants?
Variants in the DNAJB11 gene are associated with conditions that primarily affect the kidneys and liver. These include cystic kidney disease, ductal plate malformation, foetal anomalies, polycystic liver disease, and tubulointerstitial kidney disease.
How is DNAJB11 involved in protein folding?
DNAJB11 acts as a co-chaperone, interacting with Hsp70 (BiP) to stimulate its activity. This interaction is crucial for Hsp70 to efficiently bind to and assist in the proper folding of new proteins, as well as the refolding or degradation of misfolded proteins within the cell.
What does 'autosomal recessive' or 'autosomal dominant' inheritance mean for DNAJB11?
Autosomal recessive inheritance means an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the associated condition. Autosomal dominant means inheriting just one pathogenic variant copy is sufficient for condition development.
Where is the DNAJB11 gene located?
The DNAJB11 gene is located on chromosome 3. Specifically, its position is at band 3q27.3, which refers to a particular region on the long arm of chromosome 3.