GeneBe

BTRC

protein-coding

beta-transducin repeat containing E3 ubiquitin protein ligase, the group of F-box and WD repeat domain containing|WD repeat domain containing

Gene summary

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]

MANE transcript

NM_033637.4

Inheritance

—

ClinVar variants

U:82B:21

Top phenotype

BTRC-related disorder

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr10:101,354,033-101,557,321

External References & Databases

Ensembl (ENSG00000166167)NCBI Gene (8945)OMIM (603482)HGNC:1144GenCCUniProt (Q9Y297)AlphaFoldClinVar (BTRC)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~203.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BTRC variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 55
not providedTotal: 52
BTRC-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033637.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
16
clinvar
1
clinvar
 18
missense
76
clinvar
2
clinvar
2
clinvar
 80
nonsense
2
clinvar
 2
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total0082183103
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_033637.4RefSeqNP_378663.114MANE Select
ENST00000370187.8EnsemblENSP00000359206.314MANE Select
NM_001256856.2RefSeqNP_001243785.113Standard
NM_003939.5RefSeqNP_003930.113Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Circadian rhythm - Homo sapiens (human)
  • Oocyte meiosis - Homo sapiens (human)
  • Ubiquitin mediated proteolysis - Homo sapiens (human)
  • Hippo signaling pathway - Homo sapiens (human)
  • Shigellosis - Homo sapiens (human)

Biological Process

  • G2/M transition of mitotic cell cycle
  • protein polyubiquitination
  • maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)
  • protein dephosphorylation
  • ubiquitin-dependent protein catabolic process

Molecular Function

  • ubiquitin-protein transferase activity
  • protein binding
  • beta-catenin binding
  • ligase activity
  • protein phosphorylated amino acid binding

Cellular Component

  • nucleoplasm
  • cytosol
  • SCF ubiquitin ligase complex
  • small-subunit processome
  • Pwp2p-containing subcomplex of 90S preribosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000370187
Coding exons
14
Length
203259
Individuals with no LoFs
125718
Homozygous LoFs
0
Heterozygous LoFs
29
Defined
125747
p
0.000115
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.492093380.6190.00001803945
Missense (PolyPhen)3395.1120.346961132
Synonymous0.5341141210.9380.000006351152
Loss of Function4.351242.70.2810.00000280424

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American0.000150.00014rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000920.000092rare
European (Non-Finnish)0.000110.00011rare
South Asian0.0000650.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14681206, PubMed:14603323). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:10066435, PubMed:10497169, PubMed:10644755). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25704143, PubMed:25503564). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity). Has an essential role in the control of the clock- dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3 (PubMed:16371461). {ECO:0000250|UniProtKB:Q3ULA2, ECO:0000269|PubMed:10066435, ECO:0000269|PubMed:10497169, ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11238952, ECO:0000269|PubMed:11359933, ECO:0000269|PubMed:11994270, ECO:0000269|PubMed:12077367, ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:12820959, ECO:0000269|PubMed:12902344, ECO:0000269|PubMed:14603323, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988407, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16371461, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:9859996}.;

Recessive Scores

pRec
0.540

Intolerance Scores

LoFtool
0.548
RVIS EVS
-0.38
RVIS percentile EVS
27.88

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.935

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.