FNBP4

protein-coding

formin binding protein 4

Gene summary

This gene encodes a protein containing two tryptophan-rich WW domains that binds the proline-rich formin homology 1 domains of formin family proteins, suggesting a role in the regulation of cytoskeletal dynamics during cell division and migration. It also binds intersectin family proteins suggesting a role in the maintenance of membrane curvature at sites of nascent vesicle formation. Naturally occurring mutations in this gene are associated with Waardenburg anophthalmia syndrome. [provided by RefSeq, Apr 2017]

MANE transcript

NM_015308.5

Inheritance

—

ClinVar variants

U:119B:18

Top phenotype

FNBP4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr11:47,716,494-47,767,443

External References & Databases

Ensembl (ENSG00000109920)

Transcript & Mutation Effects

hg38 • Region Span ~50.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FNBP4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 102

not providedTotal: 16

FNBP4-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015308.5. 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			1 clinvar	3 clinvar	3 clinvar	7
missense			108 clinvar	5 clinvar	6 clinvar	119
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar	1 clinvar		9
Total	0	0	119	9	9	137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015308.5	RefSeq	NP_056123.2	17	MANE Select
ENST00000263773.10	Ensembl	ENSP00000263773.5	17	MANE Select
NM_001318339.4	RefSeq	NP_001305268.1	17	Standard
NM_001441100.1	RefSeq	NP_001428029.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263773
Coding exons: 17
Length: 50924
Individuals with no LoFs: 124785
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124793
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.39	438	528	0.829	0.0000259	6540
Missense (PolyPhen)		118	186.42	0.63299		2374
Synonymous	-1.41	210	186	1.13	0.00000956	2036
Loss of Function	6.46	3	54.5	0.0551	0.00000306	605

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0882

Intolerance Scores

LoFtool: 0.141
RVIS EVS: 0.51
RVIS percentile EVS: 80.24

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.963

Gene Damage Prediction

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