FBL

protein-coding

fibrillarin, the group of 7BS 2'O-ribose DNA/RNA methyltransferases|U3 small nucleolar ribonucleoprotein

Gene summary

This gene product is a component of a nucleolar small nuclear ribonucleoprotein (snRNP) particle thought to participate in the first step in processing preribosomal RNA. It is associated with the U3, U8, and U13 small nuclear RNAs and is located in the dense fibrillar component (DFC) of the nucleolus. The encoded protein contains an N-terminal repetitive domain that is rich in glycine and arginine residues, like fibrillarins in other species. Its central region resembles an RNA-binding domain and contains an RNP consensus sequence. Antisera from approximately 8% of humans with the autoimmune disease scleroderma recognize fibrillarin. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001436.4

Inheritance

—

ClinVar variants

U:43B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr19:39,834,458-39,846,379

External References & Databases

Ensembl (ENSG00000105202)

Transcript & Mutation Effects

hg38 • Region Span ~11.9 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 FBL variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001436.4. 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			3 clinvar		1 clinvar	4
missense			38 clinvar	1 clinvar		39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	43	1	1	45

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001436.4	RefSeq	NP_001427.2	9	MANE Select
ENST00000221801.8	Ensembl	ENSP00000221801.2	9	MANE Select
ENST00000594309.5	Ensembl	ENSP00000472433.1	5	Standard
ENST00000594443.5	Ensembl	ENSP00000469072.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fbl	Danio rerio	Structure: trunk Quality: decreased thickness abnormal

Gene / Model

Organism

Observed Phenotype

fbl

Danio rerio

Structure: trunk

Quality: decreased thickness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome biogenesis in eukaryotes - Homo sapiens (human)
rRNA processing
Metabolism of RNA
TNFalpha
rRNA modification in the nucleus and cytosol

Biological Process

box C/D snoRNA 3'-end processing
osteoblast differentiation
rRNA processing
rRNA methylation
snoRNA localization

Molecular Function

TFIID-class transcription factor complex binding
RNA binding
protein binding
rRNA methyltransferase activity
ATPase binding

Cellular Component

fibrillar center
dense fibrillar component
granular component
nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221801
Coding exons: 9
Length: 11957
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125710
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.20	160	209	0.767	0.0000135	2024
Missense (PolyPhen)		27	56.645	0.47665		646
Synonymous	0.449	75	80.1	0.936	0.00000514	688
Loss of Function	3.86	1	19.3	0.0519	0.00000131	191

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that has the ability to methylate both RNAs and proteins. Involved in pre-rRNA processing by catalyzing the site-specific 2'-hydroxyl methylation of ribose moieties in pre-ribosomal RNA. Site specificity is provided by a guide RNA that base pairs with the substrate. Methylation occurs at a characteristic distance from the sequence involved in base pairing with the guide RNA. Also acts as a protein methyltransferase by mediating methylation of 'Gln-105' of histone H2A (H2AQ104me), a modification that impairs binding of the FACT complex and is specifically present at 35S ribosomal DNA locus (PubMed:24352239). {ECO:0000269|PubMed:24352239}.;

Intolerance Scores

LoFtool: 0.137
RVIS EVS: -0.03
RVIS percentile EVS: 51.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

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