DNAJB11

Chr 3AD

DnaJ heat shock protein family (Hsp40) member B11

Also known as: ABBP-2, ABBP2, DJ9, Dj-9, EDJ, ERdj3, ERj3, ERj3p

NCBI Gene: 51726 ENSG00000090520 UniProt: Q9UBS4 OMIM: 611341

This gene encodes a soluble glycoprotein of the endoplasmic reticulum (ER) lumen that functions as a co-chaperone of binding immunoglobulin protein, a 70 kilodalton heat shock protein chaperone required for the proper folding and assembly of proteins in the ER. The encoded protein contains a highly conserved J domain of about 70 amino acids with a characteristic His-Pro-Asp (HPD) motif and may regulate the activity of binding immunoglobulin protein by stimulating ATPase activity. [provided by RefSeq, Mar 2014]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.521 OMIM phenotype

Clinical Summary— DNAJB11

🧬

Gene-Disease Validity (ClinGen)

ciliopathy · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

📋

ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 69 VUS of 200 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — DNAJB11

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.226

Z-score 3.15

OE 0.25 (0.13–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.77Z-score

OE missense 0.64 (0.56–0.75)

126 obs / 195.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.13–0.52)

0≤0.351.4

Missense OE?0.64 (0.56–0.75)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 5 / 20.3Missense obs/exp: 126 / 195.8Syn Z: 0.38

This gene — mechanism propensity

0.6163th %ile

GOF

0.6346th %ile

LOF

0.3649th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · 86% of P/LP variants are LoF

Literature Evidence

LOFDNAJB11 (DnaJ Heat Shock Protein Family (Hsp40) Member B11) heterozygous loss of function variations have been reported in autosomal dominant cystic kidney disease with extensive fibrosis, associated with maturation and trafficking defect involving both the autosomal dominant polycystic kidney disea1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 33129895 ↗

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic13

VUS69

Likely Benign56

Benign32

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	1	1	0	16
Likely Pathogenic	11	2	0	0	13
VUS	2	57	9	1	69
Likely Benign	0	4	37	15	56
Benign	0	1	30	1	32
Conflicting	—				4
Total	27	65	77	17	190

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

41 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap DNAJB11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →