Polycystic kidney disease 6 with or without polycystic liver disease

disease
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Also known as DNAJB11 polycystic kidney diseasePKD6polycystic kidney disease caused by mutation in DNAJB11

Summary

Polycystic kidney disease 6 with or without polycystic liver disease (MONDO:0054842) is a disease caused by DNAJB11 (GenCC Strong), with 1 cohort gene.

At a glance

  • Causal gene: DNAJB11 (GenCC Strong)
  • Cohort genes: 1
  • ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepolycystic kidney disease 6 with or without polycystic liver disease
Mondo IDMONDO:0054842
OMIM618061
DOIDDOID:0060951
UMLSC4748044
MedGen1648469
GARD0025984
Is cancer (heuristic)no

Also known as: DNAJB11 polycystic kidney disease · PKD6 · polycystic kidney disease 6 with or without polycystic liver disease · polycystic kidney disease caused by mutation in DNAJB11

Data availability: 30 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant polycystic kidney diseasepolycystic kidney disease 6 with or without polycystic liver disease

Related subtypes (6): polycystic kidney disease 1, polycystic kidney disease 3 with or without polycystic liver disease, polycystic kidney disease 2, polycystic kidney disease 7, ALG9-associated autosomal dominant polycystic kidney disease, polycystic kidney disease 8

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

30 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 9 pathogenic, 8 likely pathogenic, 1 benign, 1 conflicting classifications of pathogenicity

ClinVarVariant (HGVS)GeneClassificationReview
1172653NM_016306.6(DNAJB11):c.70C>T (p.Arg24Ter)DNAJB11Pathogeniccriteria provided, multiple submitters, no conflicts
1805387NM_016306.6(DNAJB11):c.151C>T (p.Gln51Ter)DNAJB11Pathogeniccriteria provided, single submitter
2281222NM_016306.6(DNAJB11):c.724C>T (p.Arg242Ter)DNAJB11Pathogeniccriteria provided, multiple submitters, no conflicts
3342272NM_016306.6(DNAJB11):c.258C>G (p.Tyr86Ter)DNAJB11Pathogeniccriteria provided, single submitter
3377507NM_016306.6(DNAJB11):c.537_543del (p.Gln179fs)DNAJB11Pathogeniccriteria provided, single submitter
3899993NM_016306.6(DNAJB11):c.532del (p.Thr178fs)DNAJB11Pathogeniccriteria provided, single submitter
549848NM_016306.6(DNAJB11):c.166_167insTT (p.Arg56fs)DNAJB11Pathogenicno assertion criteria provided
549849NM_016306.6(DNAJB11):c.479del (p.Ala160fs)DNAJB11Pathogeniccriteria provided, single submitter
549851NM_016306.6(DNAJB11):c.616C>T (p.Arg206Ter)DNAJB11Pathogeniccriteria provided, multiple submitters, no conflicts
3236224NM_016306.6(DNAJB11):c.635_636del (p.Ile212fs)DNAJB11Likely pathogeniccriteria provided, single submitter
3237351NM_016306.6(DNAJB11):c.544_550del (p.Pro182fs)DNAJB11Likely pathogeniccriteria provided, single submitter
3342267NM_016306.6(DNAJB11):c.763_767del (p.Arg254_Gly255insTer)DNAJB11Likely pathogeniccriteria provided, single submitter
3366872NM_016306.6(DNAJB11):c.324-1G>TDNAJB11Likely pathogenicno assertion criteria provided
3907695NM_016306.6(DNAJB11):c.926_927del (p.Asn308_Phe309insTer)DNAJB11Likely pathogeniccriteria provided, single submitter
4532219NM_016306.6(DNAJB11):c.537del (p.Gln179fs)DNAJB11Likely pathogeniccriteria provided, single submitter
549847NM_016306.6(DNAJB11):c.161C>G (p.Pro54Arg)DNAJB11Likely pathogeniccriteria provided, multiple submitters, no conflicts
549850NM_016306.6(DNAJB11):c.230T>C (p.Leu77Pro)DNAJB11Likely pathogeniccriteria provided, multiple submitters, no conflicts
4243038NM_016306.6(DNAJB11):c.500G>A (p.Arg167Gln)DNAJB11Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1098713NM_016306.6(DNAJB11):c.456+3A>GDNAJB11Uncertain significanceno assertion criteria provided
2440926NM_016306.6(DNAJB11):c.452T>G (p.Val151Gly)DNAJB11Uncertain significancecriteria provided, single submitter
2688959NM_016306.6(DNAJB11):c.600-7A>GDNAJB11Uncertain significancecriteria provided, single submitter
3068379NM_016306.6(DNAJB11):c.226-17C>GDNAJB11Uncertain significancecriteria provided, single submitter
3338402NM_016306.6(DNAJB11):c.163G>A (p.Asp55Asn)DNAJB11Uncertain significancecriteria provided, multiple submitters, no conflicts
3900722NM_016306.6(DNAJB11):c.776A>G (p.Tyr259Cys)DNAJB11Uncertain significancecriteria provided, single submitter
4077100NM_016306.6(DNAJB11):c.1012+1G>TDNAJB11Uncertain significancecriteria provided, single submitter
4531887NM_016306.6(DNAJB11):c.413T>C (p.Leu138Pro)DNAJB11Uncertain significancecriteria provided, single submitter
4540416NM_016306.6(DNAJB11):c.323+5G>ADNAJB11Uncertain significancecriteria provided, single submitter
987515NM_016306.6(DNAJB11):c.800T>C (p.Val267Ala)DNAJB11Uncertain significanceno assertion criteria provided
992421NM_016306.6(DNAJB11):c.743A>T (p.His248Leu)DNAJB11Uncertain significanceno assertion criteria provided
1250834NM_016306.6(DNAJB11):c.324-27dupDNAJB11Benigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
DNAJB11StrongAutosomal dominantpolycystic kidney disease 6 with or without polycystic liver disease7

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
DNAJB11Orphanet:730Autosomal dominant polycystic kidney disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
DNAJB11HGNC:14889ENSG00000090520Q9UBS4DnaJ homolog subfamily B member 11gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
DNAJB11DnaJ homolog subfamily B member 11As a co-chaperone for HSPA5 it is required for proper folding, trafficking or degradation of proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
DNAJB11Other/UnknownnoDnaJ_domain, DnaJ_C, HSP40/DnaJ_pept-bd

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
body of pancreas1
bone marrow cell1
vermiform appendix1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
DNAJB11141ubiquitousmarkervermiform appendix, body of pancreas, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
DNAJB113,387

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
DNAJB11Q9UBS484.34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
XBP1(S) activates chaperone genes1215.5×0.005DNAJB11
Maturation of DENV proteins1211.5×0.005DNAJB11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of ATP-dependent activity11404.3×0.002DNAJB11
mRNA modification11296.3×0.002DNAJB11
negative regulation of neurogenesis1624.1×0.003DNAJB11
protein maturation1163.6×0.008DNAJB11
protein folding1103.4×0.010DNAJB11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
DNAJB1100

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
DNAJB111Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1DNAJB11

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
DNAJB111

Clinical trials & evidence

Clinical trials

Clinical trials: 0.