SKP1
S-phase kinase associated protein 1, the group of SCF complex core subunits
Basic information
Region (hg38): 5:134148935-134176964
Previous symbols: [ "SKP1A" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SKP1 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 | 3 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 3 | 0 | 0 |
Variants in SKP1
This is a list of pathogenic ClinVar variants found in the SKP1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-134158436-A-C | Keratoconus 1 | Uncertain significance (Apr 21, 2016) | ||
| 5-134161048-A-G | not specified | Uncertain significance (Nov 14, 2024) | ||
| 5-134161060-C-T | not specified | Uncertain significance (Aug 13, 2021) | ||
| 5-134161122-C-G | not specified | Uncertain significance (May 26, 2023) | ||
| 5-134167218-A-T | not specified | Uncertain significance (Oct 01, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SKP1 | protein_coding | protein_coding | ENST00000353411 | 5 | 28097 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.373 | 0.617 | 125717 | 0 | 3 | 125720 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.66 | 16 | 85.1 | 0.188 | 0.00000400 | 1098 |
| Missense in Polyphen | 0 | 11.154 | 0 | 174 | ||
| Synonymous | -0.230 | 28 | 26.5 | 1.06 | 0.00000114 | 272 |
| Loss of Function | 2.17 | 2 | 9.02 | 0.222 | 4.64e-7 | 108 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2 (PubMed:25704143). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. {ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:20181953, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:28727686}.;
- Pathway
- Circadian rhythm - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);TNF alpha Signaling Pathway;regulation of p27 phosphorylation during cell cycle progression;TGF-beta Signaling Pathway;Notch Signaling Pathway;TLR NFkB;Degradation of beta-catenin by the destruction complex;Transcriptional regulation by RUNX2;Toll Like Receptor 7/8 (TLR7/8) Cascade;Notch;Interleukin-17 signaling;Disease;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Signaling by Interleukins;GLI3 is processed to GLI3R by the proteasome;cyclin e destruction pathway;er associated degradation (erad) pathway;e2f1 destruction pathway;Prolactin receptor signaling;Generic Transcription Pathway;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);RNA Polymerase II Transcription;Notch;Infectious disease;Hedgehog;Innate Immune System;Immune System;Cyclin D associated events in G1;G1 Phase;Adaptive Immune System;SCF(Skp2)-mediated degradation of p27/p21;Cyclin E associated events during G1/S transition ;Signaling by NOTCH1;Downstream signaling events of B Cell Receptor (BCR);Antigen processing: Ubiquitination & Proteasome degradation;Mitotic G1-G1/S phases;Transport of small molecules;Cyclin A:Cdk2-associated events at S phase entry;Orc1 removal from chromatin;DNA Replication;Switching of origins to a post-replicative state;IL-1 NFkB;Class I MHC mediated antigen processing & presentation;Signaling by NOTCH;Synthesis of DNA;S Phase;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;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;G2/M Transition;Mitotic G2-G2/M phases;G1/S Transition;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;Iron uptake and transport;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;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;NOTCH1 Intracellular Domain Regulates Transcription;Interleukin-1 family signaling;Regulation of RUNX2 expression and activity
(Consensus)
Intolerance Scores
- loftool
- 0.499
- rvis_EVS
- 0.06
- rvis_percentile_EVS
- 58
Haploinsufficiency Scores
- pHI
- 0.881
- hipred
- Y
- hipred_score
- 0.716
- ghis
- 0.404
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.539
Mouse Genome Informatics
- Gene name
- Skp1a
- Phenotype
Zebrafish Information Network
- Gene name
- skp1
- Affected structure
- anatomical system
- Phenotype tag
- abnormal
- Phenotype quality
- quality
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;protein polyubiquitination;cellular iron ion homeostasis;SCF complex assembly;negative regulation of G2/M transition of mitotic cell cycle;viral process;Wnt signaling pathway;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;histone H2A monoubiquitination;NIK/NF-kappaB signaling;post-translational protein modification;stress-activated MAPK cascade;maintenance of protein location in nucleus;interleukin-1-mediated signaling pathway;regulation of mitotic cell cycle phase transition
- Cellular component
- nucleus;nucleoplasm;cytoplasm;centrosome;cytosol;SCF ubiquitin ligase complex;Cul7-RING ubiquitin ligase complex;PcG protein complex
- Molecular function
- ubiquitin-protein transferase activity;protein binding;beta-catenin binding;protein domain specific binding;ubiquitin protein ligase activity;cullin family protein binding