FILIP1

protein-coding

filamin A interacting protein 1

Gene summary

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]

MANE transcript

NM_015687.5

Inheritance

ClinVar variants

P:6U:160B:23

Top phenotype

Neuromuscular disorder, congenital, with dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr6:75,291,859-75,493,800

External References & Databases

Ensembl (ENSG00000118407)

Transcript & Mutation Effects

hg38 • Region Span ~201.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neuromuscular disorder, congenital, with dysmorphic faciesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958332

Submitter: PanelApp Australia

neuromuscular disorder, congenital, with dysmorphic faciesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0958332

Submitter: G2P

Clinical Genomic Database (CGD)

Neuromuscular disorder, congenital, with dysmorphic faciesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36943452; 37163662

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FILIP1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 156

not providedTotal: 18

Neuromuscular disorder, congenital, with dysmorphic faciesTotal: 9

Abnormality of neuronal migrationTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015687.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	8 clinvar	2 clinvar	12
missense	1 clinvar		156 clinvar	10 clinvar	3 clinvar	170
nonsense	4 clinvar	1 clinvar	1 clinvar			6
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	5	1	160	18	5	189

Highest pathogenic variant AF is 0.000014870312

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015687.5	RefSeq	NP_056502.1	5	MANE Select
ENST00000237172.12	Ensembl	ENSP00000237172.7	5	MANE Select
NM_001289987.3	RefSeq	NP_001276916.1	6	Standard
NM_001300866.3	RefSeq	NP_001287795.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

nucleolus
cytoplasm
plasma membrane
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000237172
Coding exons: 5
Length: 201880
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 95
Defined: 125747
p: 0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	558	632	0.883	0.0000346	7950
Missense (PolyPhen)		190	219.01	0.86753		2726
Synonymous	-0.0100	242	242	1.00	0.0000140	2344
Loss of Function	3.24	24	48.3	0.497	0.00000324	597

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.0019	0.0019	notable
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00042	0.00040	rare
South Asian	0.00037	0.00036	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: By acting through a filamin-A/F-actin axis, it controls the start of neocortical cell migration from the ventricular zone. May be able to induce the degradation of filamin-A. {ECO:0000250|UniProtKB:Q8K4T4}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.852
RVIS EVS: -0.46
RVIS percentile EVS: 23.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.752

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium