FBXL19

protein-coding

F-box and leucine rich repeat protein 19, the group of Zinc fingers CXXC-type|F-box and leucine rich repeat proteins|PHD finger proteins

Gene summary

This gene encodes a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases. The encoded protein is reported to bind to the transmembrane receptor interleukin 1 receptor-like 1 and regulate its ubiquitination and degradation. This protein has been linked to the regulation of pulmonary inflammation and psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

MANE transcript

NM_001382779.1

Inheritance

—

ClinVar variants

U:75B:5

Top phenotype

Neurodevelopmental delay

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr16:30,923,055-30,948,783

External References & Databases

Ensembl (ENSG00000099364)

Transcript & Mutation Effects

hg38 • Region Span ~25.7 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 FBXL19 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 8

Neurodevelopmental delayTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001382779.1. 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	2 clinvar	2 clinvar	5
missense			69 clinvar		1 clinvar	70
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	75	2	3	80

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001382779.1	RefSeq	NP_001369708.1	10	MANE Select
ENST00000338343.10	Ensembl	ENSP00000339712.4	10	MANE Select
NM_001099784.3	RefSeq	NP_001093254.2	11	Standard
NM_001282351.1	RefSeq	NP_001269280.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

protein polyubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process
post-translational protein modification

Molecular Function

DNA binding
ubiquitin-protein transferase activity
protein binding
zinc ion binding

Cellular Component

cytosol
SCF ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380310
Coding exons: 11
Length: 25729
Individuals with no LoFs: 122681
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 122682
p: 0.00000408

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.87	189	409	0.462	0.0000282	4269
Missense (PolyPhen)		59	141.56	0.41679		1422
Synonymous	0.0281	179	179	0.997	0.0000124	1532
Loss of Function	5.05	0	29.7	0.00	0.00000195	311

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
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)	0.0000090	0.0000090	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex. {ECO:0000250}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.460
RVIS EVS: -0.07
RVIS percentile EVS: 48.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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