FILIP1

Chr 6AR

filamin A interacting protein 1

Also known as: FILIP, NMDF

NCBI Gene: 27145ENSG00000118407UniProt: Q7Z7B0

This gene encodes a filamin A binding protein. The encoded protein promotes the degradation of filamin A and may regulate cortical neuron migration and dendritic spine morphology. Mice lacking a functional copy of this gene exhibit reduced dendritic spine length and altered excitatory signaling. [provided by RefSeq, Oct 2016]

Primary Disease Associations & Inheritance

Neuromuscular disorder, congenital, with dysmorphic faciesMIM #620775
AR
192
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FILIP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 154 VUS of 192 total submissions

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.
0.70LOEUF
pLI 0.000
Z-score 3.24
OE 0.50 (0.36–0.70)
Tolerant

Typical tolerance to LoF variation

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.
1.04Z-score
OE missense 0.88 (0.82–0.95)
558 obs / 631.8 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.0.50 (0.36–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.82–0.95)
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.1.00
0≤1.21.6
LoF obs/exp: 24 / 48.3Missense obs/exp: 558 / 631.8Syn Z: -0.01

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS154
Likely Benign14
Benign5
18
Pathogenic
1
Likely Pathogenic
154
VUS
14
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
17
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
150
4
0
154
Likely Benign
0
8
1
5
14
Benign
0
3
0
2
5
Total0162237192

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

View in ClinVar →

Protein Context — Lollipop Plot

FILIP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FILIP1-related arthrogryposis multiplex congenita with microcephaly

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
stop gained NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neuromuscular disorder, congenital, with dysmorphic facies

MIM #620775

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.
Al-Kasbi G et al.·Sci Rep
2022
Bi-allelic variants of FILIP1 cause congenital myopathy, dysmorphism and neurological defects.
Roos A et al.·Brain
2023
Homozygous loss-of-function variants in FILIP1 cause autosomal recessive arthrogryposis multiplex congenita with microcephaly.
Schnabel F et al.·Hum Genet
2023
Screening and validation of atherosclerosis PAN-apoptotic immune-related genes based on single-cell sequencing.
Song Y et al.·Front Immunol
2024
Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.
arcOGEN Consortium et al.·Lancet
2012
De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature.
Becker K et al.·Eur J Med Genet
2012Review
Detection of targetable genetic alterations in SMARCA4-deficient neoplasms of the lung - further evidence of a relationship between SMARCA4-deficient undifferentiated tumor and non-small cell carcinoma.
D'Ambrosio D et al.·Hum Pathol
2026
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools