Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	26235
Gene name	F-box and leucine rich repeat protein 4
Gene symbol	FBXL4
Synonyms (NCBI Gene)	FBL4FBL5MTDPS13
Chromosome	6
Chromosome location	6q16.1-q16.2
Summary	This gene encodes a member of the F-box protein family, which are characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one subunit of modular E3 ubiquitin ligase complexes, called SCF complexes, which function in pho

Show/Hide all (60)

SNP ID	Visualize variation	Clinical significance	Consequence
rs200440128	G>A	Pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant, non coding transcript variant
rs201889294	G>A,T	Pathogenic	Coding sequence variant, non coding transcript variant, synonymous variant, stop gained, genic downstream transcript variant
rs201989042	T>G	Likely-pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant, genic downstream transcript variant
rs368965675	C>A	Pathogenic	Splice acceptor variant
rs398123059	G>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs398123060	C>G	Pathogenic-likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs398123061	G>A	Pathogenic-likely-pathogenic, likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs398123062	T>C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs747536886	A>G,T	Pathogenic, uncertain-significance	Stop gained, synonymous variant, coding sequence variant, non coding transcript variant, 5 prime UTR variant
rs747618415	T>C,G	Conflicting-interpretations-of-pathogenicity, likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant, genic downstream transcript variant
rs750973870	G>A	Likely-pathogenic	Intron variant, stop gained, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs751656896	T>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs754142863	C>A,T	Pathogenic, likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant, genic downstream transcript variant
rs758395213	G>A	Pathogenic-likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs761215749	C>-	Pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, frameshift variant
rs761902417	->T	Likely-pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, frameshift variant
rs761974928	G>A	Likely-pathogenic	5 prime UTR variant, stop gained, coding sequence variant, non coding transcript variant
rs765882664	CA>-	Pathogenic	Coding sequence variant, stop gained, inframe indel, genic downstream transcript variant, non coding transcript variant
rs766892502	GAGTA>-	Pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, frameshift variant
rs767543583	->AA	Likely-pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, frameshift variant
rs772037717	A>G	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant, non coding transcript variant
rs773850151	C>G,T	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs775768793	A>T	Likely-pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs878853112	TGCTCTGCAGAGTTGGGC>-	Likely-pathogenic	Genic downstream transcript variant, inframe deletion, coding sequence variant, non coding transcript variant
rs879255542	->T	Likely-pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs886041625	->AGTC	Pathogenic	5 prime UTR variant, frameshift variant, coding sequence variant, intron variant
rs964532159	G>A	Pathogenic	5 prime UTR variant, stop gained, intron variant, coding sequence variant
rs995995791	C>T	Likely-pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant
rs1057519447	A>G	Likely-pathogenic	Non coding transcript variant, coding sequence variant, 5 prime UTR variant, missense variant
rs1182326570	T>A	Pathogenic	Coding sequence variant, 5 prime UTR variant, stop gained, non coding transcript variant
rs1187832552	G>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant, genic downstream transcript variant
rs1227524799	C>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant, genic downstream transcript variant
rs1240941970	T>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs1257765682	C>G	Likely-pathogenic	Intron variant
rs1345325140	C>G,T	Likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant, non coding transcript variant
rs1350566881	A>G	Likely-pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, intron variant
rs1391578014	G>A	Likely-pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant
rs1394080480	C>A,T	Pathogenic	Intron variant, splice donor variant
rs1411907961	A>C	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant, genic downstream transcript variant
rs1443104983	G>T	Likely-pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs1554215766	A>T	Likely-pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1554215804	A>G	Likely-pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1554215959	T>C	Likely-pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1554215964	G>A	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, stop gained
rs1554215979	A>T	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1554215986	CT>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1554215998	T>G	Likely-pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1554216735	TTAC>-	Pathogenic	Splice donor variant, genic downstream transcript variant, intron variant
rs1554218789	C>T	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, synonymous variant
rs1554218821	G>A	Likely-pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1554219474	C>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554221189	T>A	Likely-pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, intron variant
rs1554221191	C>G	Likely-pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, intron variant
rs1554221258	C>T	Pathogenic	Splice acceptor variant, intron variant
rs1554222122	G>A	Pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, stop gained
rs1554222130	G>A	Pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, stop gained
rs1582367960	T>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant, intron variant, genic downstream transcript variant
rs1582402094	C>A	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1582425360	ATTTACT>-	Pathogenic	Coding sequence variant, 5 prime UTR variant, frameshift variant, intron variant
rs1582425406	C>A	Pathogenic	Stop gained, coding sequence variant, 5 prime UTR variant, intron variant

Show/Hide all (38)

miRTarBase ID	miRNA	Experiments	Reference
MIRT619238	hsa-miR-4795-5p	HITS-CLIP	23824327
MIRT619237	hsa-miR-4513	HITS-CLIP	23824327
MIRT619236	hsa-miR-6855-3p	HITS-CLIP	23824327
MIRT619235	hsa-miR-6857-3p	HITS-CLIP	23824327
MIRT619234	hsa-miR-5189-3p	HITS-CLIP	23824327
MIRT619233	hsa-miR-4474-5p	HITS-CLIP	23824327
MIRT619232	hsa-miR-3616-5p	HITS-CLIP	23824327
MIRT619231	hsa-miR-573	HITS-CLIP	23824327
MIRT619230	hsa-miR-3136-5p	HITS-CLIP	23824327
MIRT619229	hsa-miR-4439	HITS-CLIP	23824327
MIRT440664	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT440664	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT619238	hsa-miR-4795-5p	HITS-CLIP	23824327
MIRT619237	hsa-miR-4513	HITS-CLIP	23824327
MIRT619236	hsa-miR-6855-3p	HITS-CLIP	23824327
MIRT619235	hsa-miR-6857-3p	HITS-CLIP	23824327
MIRT619234	hsa-miR-5189-3p	HITS-CLIP	23824327
MIRT619233	hsa-miR-4474-5p	HITS-CLIP	23824327
MIRT619232	hsa-miR-3616-5p	HITS-CLIP	23824327
MIRT619231	hsa-miR-573	HITS-CLIP	23824327
MIRT619230	hsa-miR-3136-5p	HITS-CLIP	23824327
MIRT619229	hsa-miR-4439	HITS-CLIP	23824327
MIRT991129	hsa-miR-1178	CLIP-seq
MIRT991130	hsa-miR-129-5p	CLIP-seq
MIRT991131	hsa-miR-137	CLIP-seq
MIRT991132	hsa-miR-153	CLIP-seq
MIRT991133	hsa-miR-4302	CLIP-seq
MIRT991134	hsa-miR-448	CLIP-seq
MIRT991135	hsa-miR-450b-5p	CLIP-seq
MIRT991136	hsa-miR-4733-5p	CLIP-seq
MIRT991137	hsa-miR-507	CLIP-seq
MIRT991138	hsa-miR-548aa	CLIP-seq
MIRT991139	hsa-miR-557	CLIP-seq
MIRT1993910	hsa-miR-1279	CLIP-seq
MIRT1993911	hsa-miR-570	CLIP-seq
MIRT2227948	hsa-miR-3121-5p	CLIP-seq
MIRT2227949	hsa-miR-3647-3p	CLIP-seq
MIRT2227950	hsa-miR-4326	CLIP-seq

Show/Hide all (22)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000151	Component	Ubiquitin ligase complex	TAS	10531035
GO:0000422	Process	Autophagy of mitochondrion	IEA
GO:0000422	Process	Autophagy of mitochondrion	IEA
GO:0000422	Process	Autophagy of mitochondrion	IMP	32525278
GO:0000423	Process	Mitophagy	IMP	22505714
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005741	Component	Mitochondrial outer membrane	IDA	36896912
GO:0005741	Component	Mitochondrial outer membrane	IEA
GO:0005758	Component	Mitochondrial intermembrane space	IDA	23993194
GO:0005829	Component	Cytosol	TAS
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	TAS	10531035
GO:0016020	Component	Membrane	IEA
GO:0016607	Component	Nuclear speck	IDA
GO:0019005	Component	SCF ubiquitin ligase complex	IBA
GO:0031146	Process	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IBA
GO:1901525	Process	Negative regulation of mitophagy	IC	17636018
GO:1901525	Process	Negative regulation of mitophagy	IDA	38992176
GO:1990756	Function	Ubiquitin-like ligase-substrate adaptor activity	IDA	38992176

MIM	HGNC	e!Ensembl
605654	13601	ENSG00000112234

Q9UKA2

Protein name

F-box/LRR-repeat protein 4 (F-box and leucine-rich repeat protein 4) (F-box protein FBL4/FBL5)

Protein function

Substrate-recognition component of the mitochondria-localized SCF-FBXL4 ubiquitin E3 ligase complex that plays a role in the restriction of mitophagy by controlling the degradation of BNIP3 and NIX mitophagy receptors (PubMed:36896912, PubMed:38

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00646	F-box	279 → 323	F-box domain	Domain

Tissue specificity

TISSUE SPECIFICITY: Expressed in heart, kidney, liver, lung, pancreas, and placenta, but not in skeletal muscle. {ECO:0000269|PubMed:10531037}.

Sequence

MSPVFPMLTVLTMFYYICLRRRARTATRGEMMNTHRAIESNSQTSPLNAEVVQYAKEVVD
FSSHYGSENSMSYTMWNLAGVPNVFPSSGDFTQTAVFRTYGTWWDQCPSASLPFKRTPPN
FQSQDYVELTFEQQVYPTAVHVLETYHPGAVIRILACSANPYSPNPPAEVRWEILWSERP
TKVNASQARQFKPCIKQINFPTNLIRLEVNSSLLEYYTELDAVVLHGVKDKPVLSLKTSL
IDMNDIEDDAYAEKDGCGMDSLNKKFSSAVLGEGPNNGYFDKLPYELIQLILNHLTLPDL
CRLAQTCKLLSQHCCDPLQYIHLNLQPYWAKLDDTSLEFLQSRCTLVQWLNLSWTGNRGF
ISVAGFSRFLKVCGSELVRLELSCSHFLNETCLEVISEMCPNLQALNLSSCDKLPPQAFN
HIAKLCSLKRLVLYRTKVEQTALLSILNFCSELQHLSLGSCVMIEDYDVIASMIGAKCKK
LRTLDLWRCKNITENGIAELASGCPLLEELDLGWCPTLQSSTGCFTRLAHQLPNLQKLFL
TANRSVCDTDIDELACNCTRLQQLDILGTRMVSPASLRKLLESCKDLSLLDVSFCSQIDN
RAVLELNASFPKVFIKKSFTQ

Sequence length

621

Interactions

View interactions

	Reactome
			Neddylation Antigen processing: Ubiquitination & Proteasome degradation

459

Show/Hide Causal Diseases (8)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Developmental and epileptic encephalopathy, 85, with or without midline brain defects	Likely pathogenic; Pathogenic	rs398123060	RCV005861040
Global developmental delay	Likely pathogenic; Pathogenic	rs398123061	RCV000162170
Leigh syndrome	Likely pathogenic; Pathogenic	rs2128375658, rs2534899241, rs879255542, rs773850151, rs201889294, rs398123061	RCV002266444 RCV003226794 RCV003226795 RCV004800434 RCV005237491 RCV003155062
Mitochondrial DNA depletion syndrome	Likely pathogenic; Pathogenic	rs1582402094, rs201889294	RCV000825522 RCV000604628
Mitochondrial DNA depletion syndrome 13	Likely pathogenic; Pathogenic	rs2128405537, rs2128374874, rs1562245046, rs2128374840, rs1238870745, rs2128400842, rs2128378917, rs200440128, rs772037717, rs879255542, rs878853112, rs765882664, rs886041625, rs2535146567, rs1057519447 View all (43 more)	RCV001449961 RCV001542758 RCV002471120 RCV001837059 RCV001843765 RCV002267186 RCV002267200 RCV000191084 RCV000223958 RCV002283469 RCV000499866 RCV000500450 RCV000502064 RCV003983757 RCV000416414 RCV000504289 RCV000504251 RCV000500771 RCV000504456 RCV000500228 RCV000501548 RCV000502558 RCV000501986 RCV000501437 RCV000502955 RCV000502039 RCV000504527 RCV000503061 RCV000503988 RCV000499421 RCV000503199 RCV000501652 RCV000504121 RCV000499516 RCV000500730 RCV000500975 RCV000502413 RCV000501080 RCV000499569 RCV000499561 RCV000502664 RCV000504007 RCV000500625 RCV000501591 RCV000502768 RCV000500552 RCV000503270 RCV000501775 RCV000503615 RCV000499646 RCV000502743 RCV000855776 RCV000056328 RCV000056329 RCV000056330 RCV000056331 RCV000987755 RCV000991375
Mitochondrial encephalomyopathy	Likely pathogenic; Pathogenic	rs398123061	RCV000162170
Neurodevelopmental delay	Likely pathogenic; Pathogenic	rs200440128	RCV002273980
Squamous cell lung carcinoma	Pathogenic	rs1554216735	RCV005869529

Show/Hide Unknown Diseases (7)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
FBXL4-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	rs944078534, rs2535102852, rs142988015, rs748404878, rs200372976, rs377550308, rs747657121, rs573472397, rs748705687, rs895469467	RCV003909469 RCV003969693 RCV003902804 RCV003925499 RCV003915400 RCV003935320 RCV003960188 RCV003900057 RCV003900056 RCV003895612
Hepatocellular carcinoma	Benign	rs61744041	RCV005896414
Moyamoya angiopathy	Uncertain significance	rs745512025	RCV004704032
Ovarian serous cystadenocarcinoma	Benign	rs61744041	RCV005896415
Papillary renal cell carcinoma type 1	Likely benign	rs201889294	RCV005934721
Thyroid cancer, nonmedullary, 1	Benign	rs61744041	RCV005896416
Uterine corpus endometrial carcinoma	Likely benign	rs111226417	RCV005914683

Show/Hide Text Mining Associations (22)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Acidosis	Associate	32779419
Acidosis Lactic	Associate	23993193, 25868664, 31442532, 32779419
Atrophy	Associate	23993194
Brain Diseases	Associate	23993193, 25868664, 32779419
Cardiomegaly	Associate	31442532
Cardiomyopathies	Associate	31442532
Developmental Disabilities	Associate	32779419
Facial Dysmorphism with Multiple Malformations	Associate	25868664
Feeding and Eating Disorders	Associate	32779419
Hand Foot and Mouth Disease	Associate	32634583
Mitochondrial Diseases	Associate	23993193, 23993194, 25735936, 31442532, 32559514
Mitochondrial Encephalomyopathies	Associate	23993194, 31442532
Mitochondrial encephalopathy	Associate	23993193
Muscle Hypotonia	Associate	25868664, 32779419
Neoplasm Metastasis	Associate	28698647
Neoplasms	Associate	28698647
Prostatic Neoplasms	Associate	28698647
Seizures	Associate	23993194
Sleep Initiation and Maintenance Disorders	Associate	23993193, 25868664
ST Elevation Myocardial Infarction	Stimulate	26367242
Succinate Coa Ligase Deficiency	Associate	37102372
Visceral myopathy familial external ophthalmoplegia	Associate	23993193, 31442532

FBXL4 (F-box and leucine rich repeat protein 4)