FBXO28

protein-coding

F-box protein 28, the group of F-boxes other

Gene summary

Members of the F-box protein family, such as FBXO28, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_015176.4

Inheritance

ClinVar variants

P:12U:59B:16

Top phenotype

Developmental and epileptic encephalopathy 100

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr1:224,114,111-224,162,047

External References & Databases

Ensembl (ENSG00000143756)

Transcript & Mutation Effects

hg38 • Region Span ~47.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy 100STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030695

Submitter: Ambry Genetics

developmental and epileptic encephalopathy 100DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0030695

Submitter: G2P

developmental and epileptic encephalopathy 100STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030695

Submitter: PanelApp Australia

developmental and epileptic encephalopathy 100MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030695

Submitter: Illumina

developmental and epileptic encephalopathy 100STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030695

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 100AD

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30160831; 33280099

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBXO28 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 33

not providedTotal: 29

Developmental and epileptic encephalopathy 100Total: 14

FBXO28-related disorderTotal: 10

not specifiedTotal: 7

FBXO28-associated epileptic encephalopathyTotal: 1

FBXO28-related developmental and epileptic encephalopathyTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015176.4. 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				12 clinvar		12
missense	1 clinvar	3 clinvar	55 clinvar	4 clinvar		63
nonsense	2 clinvar	2 clinvar	1 clinvar			5
start loss						0
frameshift	3 clinvar	1 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	6	6	59	16	0	87

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015176.4	RefSeq	NP_055991.1	5	MANE Select
ENST00000366862.10	Ensembl	ENSP00000355827.5	5	MANE Select
NM_001136115.3	RefSeq	NP_001129587.1	4	Standard
ENST00000424254.6	Ensembl	ENSP00000416888.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

kinetochore
condensed chromosome kinetochore

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366862
Coding exons: 5
Length: 47961
Individuals with no LoFs: 125595
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125596
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.27	112	203	0.552	0.0000108	2361
Missense (PolyPhen)		16	31.186	0.51304		457
Synonymous	-0.430	78	73.3	1.06	0.00000361	737
Loss of Function	3.65	1	17.5	0.0571	0.00000104	187

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)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. {ECO:0000250}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.0770
RVIS EVS: 0.06
RVIS percentile EVS: 58.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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