FILIP1L

Chr 3

filamin A interacting protein 1 like

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

NCBI Gene: 11259 ENSG00000168386 UniProt: Q4L180

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.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in protein localization to actin cytoskeleton. Predicted to act upstream of or within several processes, including hindgut development; proteasomal protein catabolic process; and protein secretion. Predicted to be located in cytoplasm; membrane; and nucleus. Predicted to be active in actin cytoskeleton and centrosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.72

Clinical Summary— FILIP1L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

190 VUS of 212 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.51 (0.36–0.72)

0≤0.351.4

Missense OE?1.02 (0.95–1.09)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 22 / 43.3Missense obs/exp: 591 / 578.2Syn Z: 1.27

This gene — mechanism propensity

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

212 submitted variants in ClinVar

ClinVar

Classification Summary

VUS190

Likely Benign15

Benign7

190

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	190	0	0	190
Likely Benign	5	2	8	15
Benign	2	1	4	7
Total	197	3	12	212

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap FILIP1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →