FBH1

F-box DNA helicase 1, the group of F-boxes other|DNA helicases

Basic information

Region (hg38): 10:5890203-5937594

Previous symbols: [ "FBXO18" ]

Links

ENSG00000134452 ∙ NCBI:84893 ∙ OMIM:607222 ∙ HGNC:13620 ∙ Uniprot:Q8NFZ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBH1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBH1 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						0
missense			58	4		62
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	58	4	0

Variants in FBH1

This is a list of pathogenic ClinVar variants found in the FBH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-5895074-A-G		not specified	Uncertain significance (Nov 09, 2024)
10-5895109-G-T		not specified	Uncertain significance (Jul 02, 2024)
10-5895113-G-A		not specified	Uncertain significance (Oct 17, 2023)
10-5895121-G-A		not specified	Uncertain significance (Apr 22, 2022)
10-5895122-G-A		not specified	Uncertain significance (Oct 06, 2022)
10-5895140-G-A		not specified	Uncertain significance (Feb 23, 2023)
10-5895180-C-G		not specified	Uncertain significance (Mar 17, 2023)
10-5903025-C-T		not specified	Uncertain significance (Jul 23, 2024)
10-5903035-G-A		not specified	Uncertain significance (Jan 18, 2022)
10-5903059-G-A		not specified	Uncertain significance (Feb 05, 2024)
10-5903070-G-C		not specified	Uncertain significance (Nov 13, 2024)
10-5903166-G-A		not specified	Uncertain significance (Sep 04, 2024)
10-5906037-G-A		not specified	Uncertain significance (Nov 08, 2022)
10-5906037-G-T		not specified	Uncertain significance (Oct 05, 2023)
10-5906046-G-A		not specified	Uncertain significance (Jun 30, 2022)
10-5906088-C-T		not specified	Uncertain significance (Jun 10, 2022)
10-5906090-T-G		not specified	Uncertain significance (Sep 22, 2022)
10-5906097-A-G		not specified	Uncertain significance (Sep 11, 2024)
10-5906100-A-T		not specified	Uncertain significance (Jul 26, 2024)
10-5906193-A-T		not specified	Uncertain significance (Nov 29, 2021)
10-5906207-G-C		not specified	Likely benign (Oct 29, 2021)
10-5906211-C-T		not specified	Likely benign (Oct 26, 2021)
10-5906258-T-G		not specified	Uncertain significance (Oct 20, 2021)
10-5906285-G-A		not specified	Uncertain significance (Aug 05, 2024)
10-5906289-C-G		not specified	Uncertain significance (Dec 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBH1	protein_coding	protein_coding	ENST00000379999	22	48022

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000822	1.00	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.82	453	656	0.690	0.0000388	7211
Missense in Polyphen		92	216.22	0.4255		2474
Synonymous	0.493	250	260	0.961	0.0000170	2085
Loss of Function	4.69	18	55.8	0.323	0.00000289	636

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000181
Ashkenazi Jewish	0.00160	0.00159
East Asian	0.000817	0.000816
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000817	0.000816
South Asian	0.000132	0.000131
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3'-5' DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks (PubMed:11956208, PubMed:23393192). Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination (PubMed:17724085, PubMed:19736316). Also promotes cell death and DNA double-strand breakage in response to replication stress: together with MUS81, promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress (PubMed:23319600, PubMed:23361013). Plays a major role in remodeling of stalled DNA forks by catalyzing fork regression, in which the fork reverses and the two nascent DNA strands anneal (PubMed:25772361). In addition to the helicase activity, also acts as the substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex, a complex that mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular location (PubMed:25585578). {ECO:0000269|PubMed:11956208, ECO:0000269|PubMed:17724085, ECO:0000269|PubMed:19736316, ECO:0000269|PubMed:23319600, ECO:0000269|PubMed:23361013, ECO:0000269|PubMed:25585578, ECO:0000269|PubMed:25772361}.
• Disease: DISEASE: Note=Defects in FBH1 are frequently observed in melanomas, resulting in increased survival in response to replicative stress. Its inactivation may play a role in oncogenic transformation. {ECO:0000269|PubMed:23466708}.

Recessive Scores

• pRec: 0.0981

Intolerance Scores

• rvis_EVS: -2.03
• rvis_percentile_EVS: 1.68

Haploinsufficiency Scores

• pHI: 0.151
• hipred: Y
• hipred_score: 0.639
• ghis: 0.605

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Fbh1

Gene ontology

• Biological process: double-strand break repair via homologous recombination;recombinational repair;DNA catabolic process, endonucleolytic;positive regulation of protein phosphorylation;DNA repair;cellular response to DNA damage stimulus;cell death;protein ubiquitination;replication fork processing;DNA duplex unwinding;negative regulation of chromatin binding;replication fork protection;response to intra-S DNA damage checkpoint signaling;positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of double-strand break repair via homologous recombination
• Cellular component: chromatin;nucleus;SCF ubiquitin ligase complex
• Molecular function: DNA helicase activity;double-stranded DNA binding;single-stranded DNA binding;protein binding;DNA translocase activity;3'-5' DNA helicase activity;ATP-dependent 3'-5' DNA helicase activity