RBFOX1

protein-coding

RNA binding fox-1 homolog 1, the group of RNA binding motif containing|MicroRNA protein coding host genes

Gene summary

The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

MANE transcript

NM_018723.4

Inheritance

ClinVar variants

P:4U:225B:124

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr16:5,239,802-7,713,340

External References & Databases

Ensembl (ENSG00000078328)

Transcript & Mutation Effects

hg38 • Region Span ~2,473.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism susceptibility 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0020643

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

epilepsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005027

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RBFOX1 variants in ClinVar

10 Conditions Cataloged

Idiopathic generalized epilepsyTotal: 476

Inborn genetic diseasesTotal: 82

not providedTotal: 48

RBFOX1-related disorderTotal: 20

not specifiedTotal: 17

Self-limited epilepsy with centrotemporal spikesTotal: 4

Neurodevelopmental disorderTotal: 1

Intellectual disability, autosomal dominant 46Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018723.4. 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			1 clinvar	109 clinvar	8 clinvar	118
missense		3 clinvar	204 clinvar	6 clinvar	1 clinvar	214
nonsense			10 clinvar			10
start loss						0
frameshift	1 clinvar		4 clinvar			5
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	3	225	115	9	353

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018723.4	RefSeq	NP_061193.2	13	MANE Select
ENST00000550418.6	Ensembl	ENSP00000450031.1	13	MANE Select
NM_001142333.2	RefSeq	NP_001135805.1	12	Standard
NM_001142334.2	RefSeq	NP_001135806.1	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rbfox1	Danio rerio	Structure: atrium Quality: dilated abnormal

Gene / Model

Organism

Observed Phenotype

rbfox1

Danio rerio

Structure: atrium

Quality: dilated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MECP2 and Associated Rett Syndrome

Biological Process

regulation of alternative mRNA splicing, via spliceosome
mRNA processing
nervous system development
RNA splicing
RNA transport

Molecular Function

RNA binding
mRNA binding
protein binding
protein C-terminus binding

Cellular Component

nucleus
cytoplasm
trans-Golgi network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311745
Coding exons: 13
Length: 1694246
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125733
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.196	271	280	0.967	0.0000185	2661
Missense (PolyPhen)		98	107.7	0.90995		1063
Synonymous	-3.41	175	126	1.39	0.0000101	858
Loss of Function	4.12	4	27.2	0.147	0.00000159	272

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000044	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis. {ECO:0000269|PubMed:16537540}.;

Intolerance Scores

RVIS EVS: -0.47
RVIS percentile EVS: 23.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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