DNAJC27

Chr 2

DnaJ heat shock protein family (Hsp40) member C27

Also known as: RBJ, RabJS

The protein functions as a GTPase that can activate the MEK/ERK pathway and may serve as a nuclear scaffold for MAPK1 to enhance ERK1/ERK2 signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene shows low constraint to loss-of-function variation based on population genetics data.

Summary from RefSeq, UniProt
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0
Active trials
5
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.89
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryDNAJC27
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.001
Z-score 1.86
OE 0.48 (0.270.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.48Z-score
OE missense 0.89 (0.781.02)
142 obs / 159.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.270.89)
00.351.4
Missense OE0.89 (0.781.02)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 7 / 14.7Missense obs/exp: 142 / 159.2Syn Z: 0.75
DN
0.82top 10%
GOF
0.80top 10%
LOF
0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DNAJC27 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC