FBXO38

F-box protein 38, the group of F-boxes other

Basic information

Region (hg38): 5:148383934-148442836

Links

ENSG00000145868 ∙ NCBI:81545 ∙ OMIM:608533 ∙ HGNC:28844 ∙ Uniprot:Q6PIJ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• distal hereditary motor neuropathy type 2 (Supportive), mode of inheritance: AD
• distal hereditary motor neuropathy (Moderate), mode of inheritance: AD
• neuronopathy, distal hereditary motor, type 2D (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal dominant 6	AD	General	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	Neurologic	7723953; 24207122

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXO38 gene.

• Distal hereditary motor neuropathy type 2 (503 variants)
• Inborn genetic diseases (78 variants)
• not provided (73 variants)
• Neuronopathy, distal hereditary motor, type 2D (25 variants)
• not specified (7 variants)
• Charcot-Marie-Tooth disease (1 variants)
• Distal spinal muscular atrophy (1 variants)
• FBXO38-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXO38 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	114	8	130
missense	1		280	20	3	304
nonsense			5			5
start loss			1			1
frameshift			1			1
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)			2			2
splice region			9	19	5	33
non coding			1	68	32	101
Total	1	0	300	202	44

Variants in FBXO38

This is a list of pathogenic ClinVar variants found in the FBXO38 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-148394777-A-G		Distal hereditary motor neuropathy type 2	Uncertain significance (Aug 16, 2022)
5-148394780-G-A		Distal hereditary motor neuropathy type 2 • not specified	Uncertain significance (Mar 20, 2022)
5-148394787-G-A		Neuronopathy, distal hereditary motor, type 2D • Distal hereditary motor neuropathy type 2 • not specified	Conflicting classifications of pathogenicity (Dec 11, 2023)
5-148394789-A-C		Distal hereditary motor neuropathy type 2	Uncertain significance (Sep 13, 2022)
5-148394793-A-G		Distal hereditary motor neuropathy type 2 • not specified	Uncertain significance (Jun 07, 2023)
5-148394798-G-A		Distal hereditary motor neuropathy type 2	Uncertain significance (Jul 26, 2022)
5-148394803-A-G		Distal hereditary motor neuropathy type 2	Likely benign (Nov 17, 2023)
5-148394810-A-G		Distal hereditary motor neuropathy type 2	Uncertain significance (Jan 24, 2024)
5-148394813-A-T		Distal hereditary motor neuropathy type 2	Uncertain significance (Nov 26, 2022)
5-148394818-T-G		not specified	Uncertain significance (Dec 06, 2019)
5-148394821-T-C		Distal hereditary motor neuropathy type 2	Likely benign (Sep 23, 2020)
5-148394827-T-C		Distal hereditary motor neuropathy type 2	Likely benign (Jul 18, 2022)
5-148394830-A-G		Distal hereditary motor neuropathy type 2	Likely benign (Jun 03, 2019)
5-148394837-A-G		Distal hereditary motor neuropathy type 2	Uncertain significance (Mar 25, 2021)
5-148394838-T-C		Distal hereditary motor neuropathy type 2	Uncertain significance (Jan 08, 2024)
5-148394845-A-G		Distal hereditary motor neuropathy type 2	Likely benign (Aug 01, 2023)
5-148394847-A-G		Distal hereditary motor neuropathy type 2	Uncertain significance (May 30, 2022)
5-148394862-A-G		Distal hereditary motor neuropathy type 2	Uncertain significance (Dec 14, 2023)
5-148394863-T-C		not specified • Distal hereditary motor neuropathy type 2 • FBXO38-related disorder	Benign/Likely benign (Jan 31, 2024)
5-148394867-A-C		Distal hereditary motor neuropathy type 2 • Neuronopathy, distal hereditary motor, type 2D • not specified	Conflicting classifications of pathogenicity (May 12, 2023)
5-148394893-C-T		Distal hereditary motor neuropathy type 2	Likely benign (Jul 07, 2023)
5-148394910-A-G		Distal hereditary motor neuropathy type 2	Uncertain significance (Jan 19, 2024)
5-148394913-G-T		Distal hereditary motor neuropathy type 2	Likely benign (Jan 01, 2021)
5-148394923-G-A		Distal hereditary motor neuropathy type 2	Likely benign (Jan 11, 2024)
5-148395099-T-G			Benign (Mar 08, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXO38	protein_coding	protein_coding	ENST00000394370	21	58902

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00121	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.81	425	622	0.683	0.0000338	7364
Missense in Polyphen		260	419.68	0.61952		5006
Synonymous	0.563	204	214	0.951	0.0000114	2073
Loss of Function	6.05	9	59.2	0.152	0.00000354	672

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000124
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000549	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000721	0.0000703
Middle Eastern	0.0000549	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. May coactivate KLF7, but does not seem to promote KLF7 ubiquitination (By similarity). {ECO:0000250}.
• Disease: DISEASE: Neuronopathy, distal hereditary motor, 2D (HMN2D) [MIM:615575]: A disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles. Some patients may lose independent ambulation later in the disease course. Sensory impairment is typically not present, and cognition and bulbar function are normal. {ECO:0000269|PubMed:24207122}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.508
• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.5

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.613
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.895

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbxo38

Gene ontology

• Biological process: positive regulation of neuron projection development
• Cellular component: nucleus;cytoplasm