FILIP1L

Chr 3

filamin A interacting protein 1 like

Also known as: DOC-1, DOC1, GIP130, GIP90

NCBI Gene: 11259ENSG00000168386UniProt: Q4L180OMIM: 612993

The protein regulates antiangiogenic activity in endothelial cells and inhibits cell proliferation, migration, and tumor growth. Mutations in this gene cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.725), suggesting some tolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.72
Clinical Summary— FILIP1L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 199 VUS of 232 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.000
Z-score 3.00
OE 0.51 (0.36–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.19Z-score
OE missense 1.02 (0.95–1.09)
591 obs / 578.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.36–0.72)
0≤0.351.4
Missense OE1.02 (0.95–1.09)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 22 / 43.3Missense obs/exp: 591 / 578.2Syn Z: 1.27
DN
0.75top 25%
GOF
0.6930th %ile
LOF
0.3357th %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

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS199
Likely Benign16
Benign7
7
Pathogenic
3
Likely Pathogenic
199
VUS
16
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
0
190
9
0
199
Likely Benign
0
5
3
8
16
Benign
0
2
1
4
7
Total01972312232

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

View in ClinVar →

Protein Context — Lollipop Plot

FILIP1L · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Smoking-associated Downregulation of FILIP1L Enhances Lung Adenocarcinoma Progression Through Mucin Production, Inflammation, and Fibrosis.
Kwon M et al.·Cancer Res Commun
2022
An integrated approach for key gene selection and cancer phenotype classification: Improving diagnosis and prediction.
Rahaman MM et al.·Comput Biol Med
2025
Reduced expression of FILIP1L, a novel WNT pathway inhibitor, is associated with poor survival, progression and chemoresistance in ovarian cancer.
Kwon M et al.·Oncotarget
2016
Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and TP53 Mutation Status in Triple-Negative Cases.
Sadzeviciene I et al.·Int J Mol Sci
2022Cohort
Nodular fasciitis: a case series unveiling novel and rare gene fusions, including two cases with aggressive clinical behavior.
Saoud C et al.·Virchows Arch
2025Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients