STIP1

Chr 11

stress induced phosphoprotein 1

ENSG00000168439UniProt: P31948

Acts as a co-chaperone for HSP90AA1 (PubMed:27353360). Mediates the association of the molecular chaperones HSPA8/HSC70 and HSP90 (By similarity)

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— STIP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.20LOEUF
pLI 1.000
Z-score 5.31
OE 0.08 (0.03–0.20)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.92Z-score
OE missense 0.70 (0.63–0.78)
223 obs / 319.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.63–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 3 / 38.6Missense obs/exp: 223 / 319.6Syn Z: -1.14

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

STIP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration.
Rusmini P et al.·Autophagy
2019Functional
Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction.
Schiattarella GG et al.·Nat Commun
2021
Prognostic significance of STIP1 expression in human cancer: A meta-analysis.
Zhang S et al.·Clin Chim Acta
2018Review
HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.
Tedesco B et al.·Autophagy
2023
Proteomic biomarkers in psoriatic arthritis.
Scalcon MRR et al.·Clin Chim Acta
2025Review
Expression and clinical significance of STIP1 in papillary thyroid carcinoma.
Yuan MH et al.·Tumour Biol
2014
Clinical and functional characterization of a novel STUB1 mutation in a Chinese spinocerebellar ataxia 48 pedigree.
Li J et al.·Orphanet J Rare Dis
2024Functional
Autocrine STIP1 signaling promotes tumor growth and is associated with disease outcome in hepatocellular carcinoma.
Chen Z et al.·Biochem Biophys Res Commun
2017
Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia.
Ravel JM et al.·J Neurol
2021
STIP1 knockdown suppresses colorectal cancer cell proliferation, migration and invasion by inhibiting STAT3 pathway.
Xia Y et al.·Chem Biol Interact
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Stress-inducible phosphoprotein 1 (STIP1) is a critical stemness regulator in mouse embryonic stem cells and early mammalian development.
Fernandes CFL et al.·Commun Biol
2025🔓 Open AccessFunctional
STIP1 drives Metabolic Reprogramming in Esophageal Squamous Cell Carcinoma via AHCY-LDHA Axis.
Jin G et al.·Exploration (Beijing)
2025🔓 Open Access
Doublecortin-like kinase 1, regulated by STIP1 homology and U-box containing protein 1 or Sp1 transcription factor, affects the malignant behaviors and drug sensitivity in adriamycin-resistant breast cancer cells.
Cheng L et al.·Naunyn Schmiedebergs Arch Pharmacol
2025
Stress-inducible phosphoprotein 1 (Sti1/Stip1/Hop) sequesters misfolded proteins during stress.
Rutledge BS et al.·FEBS J
2025🔓 Open Access
GOLPH3-STIP1 Complex Activates STAT3 Through Exosome Secretion to Induce Colon Cancer Metastasis.
Guo Y et al.·Biotechnol J
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools