HYOU1

Chr 11

hypoxia up-regulated 1

Also known as: GRP-170, Grp170, HSP12A, IMD59, ORP-150, ORP150

The protein encoded by this gene belongs to the heat shock protein 70 family. This gene uses alternative transcription start sites. A cis-acting segment found in the 5' UTR is involved in stress-dependent induction, resulting in the accumulation of this protein in the endoplasmic reticulum (ER) under hypoxic conditions. The protein encoded by this gene is thought to play an important role in protein folding and secretion in the ER. Since suppression of the protein is associated with accelerated apoptosis, it is also suggested to have an important cytoprotective role in hypoxia-induced cellular perturbation. This protein has been shown to be up-regulated in tumors, especially in breast tumors, and thus it is associated with tumor invasiveness. This gene also has an alternative translation initiation site, resulting in a protein that lacks the N-terminal signal peptide. This signal peptide-lacking protein, which is only 3 amino acids shorter than the mature protein in the ER, is thought to have a housekeeping function in the cytosol. In rat, this protein localizes to both the ER by a carboxy-terminal peptide sequence and to mitochondria by an amino-terminal targeting signal. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtImmunodeficiency 59 and hypoglycemia

Clinical highlights

Gene–disease validity (ClinGen)
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
28
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.33
LOEUF· LoF intol.
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.33LOEUF
pLI 0.861
Z-score 5.49
OE 0.20 (0.13–0.33)
Highly constrained

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

Missense Constraint?
1.80Z-score
OE missense 0.79 (0.73–0.85)
472 obs / 595.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.13–0.33)
0≤0.351.4
Missense OE?0.79 (0.73–0.85)
0≤0.61.4
Synonymous OE?1.04
0≤1.21.6
LoF obs/exp: 11 / 54.9Missense obs/exp: 472 / 595.7Syn Z: -0.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HYOU1 · 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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