FBXO31

protein-coding

F-box protein 31, the group of F-boxes other

Gene summary

This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MANE transcript

NM_024735.5

Inheritance

AR, AD

ClinVar variants

P:3U:90B:26

Top phenotype

Intellectual developmental disorder, autosomal recessive 45

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr16:87,326,987-87,392,142

External References & Databases

Ensembl (ENSG00000103264)

Transcript & Mutation Effects

hg38 • Region Span ~65.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

cerebral palsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0006497

Submitter: Ambry Genetics

intellectual disability, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100597

Submitter: Ambry Genetics

cerebral palsySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0006497

Submitter: PanelApp Australia

intellectual disability, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100597

Submitter: PanelApp Australia

intellectual developmental disorder, autosomal recessive 45LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014430

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 45AR

Manifestation: Craniofacial; 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: 24623383

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBXO31 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 27

FBXO31-related disorderTotal: 10

Intellectual disability, autosomal recessive 45Total: 7

Ectopic thyroidTotal: 1

Spastic cerebral palsyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024735.5. 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			5 clinvar	20 clinvar	3 clinvar	28
missense		1 clinvar	78 clinvar	3 clinvar		82
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		1 clinvar	5 clinvar			6
Total	1	2	90	23	3	119

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024735.5	RefSeq	NP_079011.3	9	MANE Select
ENST00000311635.12	Ensembl	ENSP00000310841.4	9	MANE Select
NM_001282683.2	RefSeq	NP_001269612.1	6	Standard
ENST00000565593.1	Ensembl	ENSP00000455772.1	2	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
cellular response to DNA damage stimulus
anaphase-promoting complex-dependent catabolic process
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
mitotic G1 DNA damage checkpoint

Molecular Function

ubiquitin-protein transferase activity
protein binding
cyclin binding

Cellular Component

centrosome
cytosol
SCF ubiquitin ligase complex
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311635
Coding exons: 9
Length: 65156
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.46	214	342	0.626	0.0000229	3483
Missense (PolyPhen)		45	142.71	0.31532		1479
Synonymous	-0.443	159	152	1.05	0.0000111	1091
Loss of Function	3.48	5	23.0	0.217	0.00000125	247

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. Specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest. May act as a tumor suppressor. {ECO:0000269|PubMed:16357137, ECO:0000269|PubMed:19412162}.;
Disease: DISEASE: Mental retardation, autosomal recessive 45 (MRT45) [MIM:615979]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT45 manifestations include mild to moderate intellectual disability and dysmorphic features, including coarse facies, broad nasal bridge, fleshy nares, and thick, prominent lips. {ECO:0000269|PubMed:24623383}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.0902
RVIS EVS: -0.82
RVIS percentile EVS: 11.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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