BTRC

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

Basic information

Region (hg38): 10:101354032-101557321

Links

ENSG00000166167 ∙ NCBI:8945 ∙ OMIM:603482 ∙ HGNC:1144 ∙ Uniprot:Q9Y297 ∙ 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 BTRC gene.

• not provided (36 variants)
• Inborn genetic diseases (16 variants)
• BTRC-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BTRC 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				10	1	11
missense			25	2	3	30
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	2	5
non coding				3		3
Total	0	0	28	15	4

Variants in BTRC

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

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

Position	Type	Phenotype	Significance	ClinVar
10-101354173-C-T		BTRC-related disorder	Likely benign (Apr 23, 2019)
10-101354217-C-A			Uncertain significance (Aug 24, 2022)
10-101430339-C-T			Likely benign (Aug 31, 2022)
10-101430341-G-T			Likely benign (Aug 31, 2022)
10-101430372-G-T		not specified	Uncertain significance (Dec 08, 2023)
10-101430373-G-A		not specified	Uncertain significance (Aug 08, 2023)
10-101430435-G-A			Uncertain significance (Aug 09, 2023)
10-101462003-G-A		not specified	Uncertain significance (Sep 15, 2021)
10-101462017-C-A		not specified	Uncertain significance (Jun 29, 2023)
10-101462056-C-A			Uncertain significance (Sep 01, 2021)
10-101479389-C-T		not specified	Uncertain significance (Aug 17, 2023)
10-101479416-T-G			Uncertain significance (Apr 12, 2022)
10-101479419-G-C			Uncertain significance (May 04, 2022)
10-101521664-G-A			Uncertain significance (May 14, 2022)
10-101521675-C-T		not specified	Uncertain significance (Mar 04, 2024)
10-101521818-A-T			Likely benign (Feb 03, 2022)
10-101521824-G-A			Likely benign (Oct 22, 2022)
10-101521831-A-T			Uncertain significance (May 09, 2018)
10-101521840-T-A		not specified	Uncertain significance (Dec 26, 2023)
10-101521857-A-G		not specified	Uncertain significance (Jan 08, 2024)
10-101521877-C-G		BTRC-related disorder	Benign (Jan 29, 2024)
10-101526143-C-T		BTRC-related disorder	Benign (Jan 31, 2024)
10-101531245-A-C		not specified	Uncertain significance (Sep 28, 2021)
10-101531288-C-T			Likely benign (Dec 18, 2023)
10-101531343-T-A			Likely benign (Sep 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BTRC	protein_coding	protein_coding	ENST00000370187	14	203259

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0119	0.988	125718	0	29	125747	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.49	209	338	0.619	0.0000180	3945
Missense in Polyphen		33	95.112	0.34696		1132
Synonymous	0.534	114	121	0.938	0.00000635	1152
Loss of Function	4.35	12	42.7	0.281	0.00000280	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000454	0.000454
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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);Wnt signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);WNT-Ncore;HH-Ncore;TNF alpha Signaling Pathway;TGF-beta Signaling Pathway;TLR NFkB;Degradation of beta-catenin by the destruction complex;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Signaling by WNT;Signal Transduction;Signaling by Interleukins;Circadian Clock;GLI3 is processed to GLI3R by the proteasome;wnt signaling pathway;Prolactin receptor signaling;Prolactin;NIK-->noncanonical NF-kB signaling;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;Host Interactions of HIV factors;HIV Infection;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Post-translational protein modification;Activation of NF-kappaB in B cells;Metabolism of proteins;Signaling by the B Cell Receptor (BCR);Interleukin-1 signaling;Dectin-1 mediated noncanonical NF-kB signaling;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Notch;Infectious disease;Hedgehog;Innate Immune System;Immune System;Adaptive Immune System;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Downstream signaling events of B Cell Receptor (BCR);Antigen processing: Ubiquitination & Proteasome degradation;IL-1 NFkB;Class I MHC mediated antigen processing & presentation;Degradation of GLI2 by the proteasome;Degradation of GLI1 by the proteasome;Hedgehog ,off, state;Signaling by Hedgehog;TGF_beta_Receptor;Regulation of PLK1 Activity at G2/M Transition;MAP3K8 (TPL2)-dependent MAPK1/3 activation;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Neddylation;MyD88 dependent cascade initiated on endosome;Validated transcriptional targets of TAp63 isoforms;G2/M Transition;Mitotic G2-G2/M phases;SCF-beta-TrCP mediated degradation of Emi1;Regulation of APC/C activators between G1/S and early anaphase;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;TNFalpha;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Vpu mediated degradation of CD4;Cell Cycle, Mitotic;Wnt Canonical;Canonical NF-kappaB pathway;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Regulation of nuclear beta catenin signaling and target gene transcription;Degradation of beta catenin;Wnt Mammals;Signaling events mediated by HDAC Class I;Hedgehog signaling events mediated by Gli proteins;Alternative NF-kappaB pathway;Presenilin action in Notch and Wnt signaling;Atypical NF-kappaB pathway;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.540

Intolerance Scores

• loftool: 0.548
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.88

Haploinsufficiency Scores

• pHI: 0.300
• hipred: Y
• hipred_score: 0.765
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.935

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Btrc
• Phenotype: immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• 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;signal transduction;viral process;Wnt signaling pathway;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;protein destabilization;mammary gland epithelial cell proliferation;NIK/NF-kappaB signaling;regulation of circadian rhythm;positive regulation of circadian rhythm;regulation of I-kappaB kinase/NF-kappaB signaling;proteasome-mediated ubiquitin-dependent protein catabolic process;negative regulation of DNA-binding transcription factor activity;post-translational protein modification;positive regulation of proteolysis;negative regulation of smoothened signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;rhythmic process;stress-activated MAPK cascade;branching involved in mammary gland duct morphogenesis;regulation of canonical Wnt signaling pathway;regulation of proteasomal protein catabolic process;interleukin-1-mediated signaling pathway;cellular response to organic cyclic compound;regulation of mitotic cell cycle phase transition
• Cellular component: nucleoplasm;cytosol;SCF ubiquitin ligase complex;small-subunit processome;Pwp2p-containing subcomplex of 90S preribosome
• Molecular function: ubiquitin-protein transferase activity;protein binding;beta-catenin binding;ligase activity;protein phosphorylated amino acid binding;protein dimerization activity;ubiquitin protein ligase activity