FBXO44

protein-coding

F-box protein 44, the group of F-boxes other

Gene summary

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. It is also a member of the NFB42 (neural F Box 42 kDa) family, similar to F-box only protein 2 and F-box only protein 6. Several alternatively spliced transcript variants encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

MANE transcript

NM_033182.7

Inheritance

—

ClinVar variants

U:45B:23

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr1:11,654,375-11,663,327

External References & Databases

Ensembl (ENSG00000132879)

Transcript & Mutation Effects

hg38 • Region Span ~9.0 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 FBXO44 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 66

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033182.7. 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				23 clinvar		23
missense			43 clinvar			43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	45	23	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033182.7	RefSeq	NP_149438.2	5	MANE Select
ENST00000251547.10	Ensembl	ENSP00000251547.5	5	MANE Select
NM_001014765.2	RefSeq	NP_001014765.1	5	Standard
NM_001304790.2	RefSeq	NP_001291719.1	4	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
proteasomal protein catabolic process
post-translational protein modification

Molecular Function

ubiquitin-protein transferase activity
protein binding

Cellular Component

cytosol
SCF ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376770
Coding exons: 5
Length: 8953
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125747
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.353	159	172	0.924	0.0000120	1672
Missense (PolyPhen)		82	80.962	1.0128		809
Synonymous	-0.107	83	81.8	1.01	0.00000651	491
Loss of Function	1.16	11	16.0	0.688	8.39e-7	147

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00016	0.00016	rare
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.;

Intolerance Scores

LoFtool: 0.937
RVIS EVS: 0.22
RVIS percentile EVS: 68.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.662

Gene Damage Prediction

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