FILIP1

Chr 6AR

filamin A interacting protein 1

Also known as: FILIP, NMDF

NCBI Gene: 27145 ENSG00000118407 UniProt: Q7Z7B0 OMIM: 607307

This protein binds to and promotes degradation of filamin A, regulating cortical neuron migration and dendritic spine morphology during brain development. Biallelic mutations cause autosomal recessive congenital neuromuscular disorder with dysmorphic facial features. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neuromuscular disorder, congenital, with dysmorphic faciesMIM #620775

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neuromuscular disorder, congenital, with dysmorphic facies; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.000

Z-score 3.24

OE 0.50 (0.36–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.04Z-score

OE missense 0.88 (0.82–0.95)

558 obs / 631.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.36–0.70)

0≤0.351.4

Missense OE?0.88 (0.82–0.95)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 24 / 48.3Missense obs/exp: 558 / 631.8Syn Z: -0.01

Background carrier burden — how many people carry a rare variant somewhere in FILIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

1,426 rare PASS variants

Rare truncating (LoF)

1 in 690

172 rare PASS variants

Rare synonymous (reference)

1 in 110

530 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FILIP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 71	1 in 790
South Asian	~43k	1 in 38	1 in 770
Remaining (unassigned)	~30k	1 in 45	1 in 370
European (Finnish)	~27k	1 in 200	1 in 2,600
Admixed American	~22k	1 in 44	1 in 750
African / African American	~21k	1 in 35	1 in 700
East Asian	~20k	1 in 41	1 in 1,300
Ashkenazi Jewish	~13k	1 in 200	1 in 2,200
Middle Eastern	~2,884	1 in 34	1 in 470

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓