DNAJC2

Chr 7

DnaJ heat shock protein family (Hsp40) member C2

Also known as: MPHOSPH11, MPP11, ZRF1, ZUO1

NCBI Gene: 27000 ENSG00000105821 UniProt: Q99543 OMIM: 605502

The protein functions as a molecular chaperone that assists nascent polypeptide folding at ribosomes in the cytosol and regulates chromatin by displacing polycomb repressor complexes in the nucleus. Mutations cause spastic paraplegia with intellectual disability through autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric complex that associates with ribosomes, acting as a molecular chaperone for nascent polypeptide chains as they exit the ribosome. This protein was identified as a leukemia-associated antigen and expression of the gene is upregulated in leukemic blasts. Also, chromosomal aberrations involving this gene are associated with primary head and neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.29

Clinical Summary— DNAJC2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

63 VUS of 86 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.991

Z-score 5.03

OE 0.15 (0.08–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.52Z-score

OE missense 0.76 (0.68–0.84)

234 obs / 309.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.29)

0≤0.351.4

Missense OE?0.76 (0.68–0.84)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 40.6Missense obs/exp: 234 / 309.2Syn Z: 0.56

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS63

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	63	0	63
Likely Benign	0	0	0
Benign	0	1	1
Total	63	1	64

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap DNAJC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →