WIF1

Chr 12

Wnt inhibitory factor 1

Also known as: WIF-1

NCBI Gene: 11197ENSG00000156076UniProt: Q9Y5W5

The protein encoded by this gene functions to inhibit WNT proteins, which are extracellular signaling molecules that play a role in embryonic development. This protein contains a WNT inhibitory factor (WIF) domain and five epidermal growth factor (EGF)-like domains, and is thought to be involved in mesoderm segmentation. This gene functions as a tumor suppressor gene, and has been found to be epigenetically silenced in various cancers. [provided by RefSeq, Jun 2010]

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— WIF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.09LOEUF
pLI 0.000
Z-score 1.22
OE 0.73 (0.50–1.09)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.48Z-score
OE missense 0.91 (0.80–1.02)
185 obs / 204.1 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.0.73 (0.50–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.80–1.02)
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.0.96
0≤1.21.6
LoF obs/exp: 17 / 23.4Missense obs/exp: 185 / 204.1Syn Z: 0.24

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

WIF1 · 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
HMGA2-WIF1 Rearrangements Characterize a Distinctive Subset of Salivary Pleomorphic Adenomas With Prominent Trabecular (Canalicular Adenoma-like) Morphology.
Agaimy A et al.·Am J Surg Pathol
2022
USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction.
Kim MJ et al.·Cell Death Dis
2022
Early ctDNA and Survival in Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors: A Secondary Analysis of the SAMCO-PRODIGE 54 Randomized Clinical Trial.
Taïeb J et al.·JAMA Oncol
2025
Wif1 Mediates Coordination of Bone Morphogenetic Protein and Wnt Signaling in Neural and Glioma Stem Cells.
Xu C et al.·Cell Transplant
2022
Pathological oligodendrocyte precursor cells revealed in human schizophrenic brains and trigger schizophrenia-like behaviors and synaptic defects in genetic animal model.
Yu G et al.·Mol Psychiatry
2022Functional
Multitranscriptome analysis reveals stromal cells in the papillary dermis to promote angiogenesis in psoriasis vulgaris.
Zhang B et al.·Br J Dermatol
2025
DNA methylation of SFRP1, SFRP2, and WIF1 and prognosis of postoperative colorectal cancer patients.
Liu X et al.·BMC Cancer
2019Cohort
COLEC10 inhibits the stemness of hepatocellular carcinoma by suppressing the activity of β-catenin signaling.
Cai MN et al.·Cell Oncol (Dordr)
2024
Beneath HMGA2 alterations in pleomorphic adenomas: Pathological, immunohistochemical, and molecular insights.
Alsugair Z et al.·Hum Pathol
2024
Expanding the Molecular-genetic Spectrum of Canalicular Adenoma-like Subtype of Pleomorphic Adenoma of Salivary Glands.
Klubíčková N et al.·Am J Surg Pathol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Metastatic Colon Cancer

De-scalation or swItch of Treatment According to Circulating tuMOr DNA Variation After 2 Cycles of Doublet Chemotherapy Plus Targeted Agent in Metastatic Unresectable Colorectal Cancer

NOT YET RECRUITING
NCT06446557Phase PHASE3University Hospital, RouenStarted 2026-06
treatment adaptation guided by ctDNA variationstandard management

External Resources

Links to major genomics databases and tools