FBN3

protein-coding

fibrillin 3, the group of Fibrillins

Gene summary

This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

MANE transcript

NM_032447.5

Inheritance

—

ClinVar variants

U:918B:449

Top phenotype

FBN3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr19:8,065,402-8,149,592

External References & Databases

Ensembl (ENSG00000142449)

Transcript & Mutation Effects

hg38 • Region Span ~84.2 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 FBN3 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 1286

not specifiedTotal: 549

FBN3-related disorderTotal: 144

Flexion contractureTotal: 2

Weill-Marchesani syndromeTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032447.5. 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			13 clinvar	271 clinvar	49 clinvar	333
missense			850 clinvar	99 clinvar	29 clinvar	978
nonsense			21 clinvar			21
start loss						0
frameshift			18 clinvar			18
splice donor/acceptor (+/-2bp)			16 clinvar	1 clinvar		17
Total	0	0	918	371	78	1367

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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_032447.5	RefSeq	NP_115823.3	63	MANE Select
ENST00000600128.6	Ensembl	ENSP00000470498.1	63	MANE Select
NM_001321431.2	RefSeq	NP_001308360.1	63	Standard
ENST00000270509.6	Ensembl	ENSP00000270509.2	63	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hypothesized Pathways in Pathogenesis of Cardiovascular Disease
Extracellular matrix organization
Elastic fibre formation

Molecular Function

extracellular matrix structural constituent
calcium ion binding

Cellular Component

extracellular matrix
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000600128
Coding exons: 63
Length: 84445
Individuals with no LoFs: 125369
Homozygous LoFs: 0
Heterozygous LoFs: 379
Defined: 125748
p: 0.00151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.958	1653	1.77e+3	0.936	0.000117	18370
Missense (PolyPhen)		595	658.55	0.9035		7325
Synonymous	-0.0775	725	722	1.00	0.0000510	5387
Loss of Function	4.19	90	144	0.624	0.00000760	1585

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0042	0.0041	notable
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.0020	0.0019	notable
Finnish	0.00062	0.00060	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.0016	0.0016	notable
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Fibrillin-3: Fibrillins are structural components of 10- 12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. Fibrillin-containing microfibrils provide long-term force bearing structural support. {ECO:0000269|PubMed:14962672}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.0141
RVIS EVS: 7.07
RVIS percentile EVS: 99.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.123

Gene Damage Prediction

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