SKP2

S-phase kinase associated protein 2, the group of F-box and leucine rich repeat proteins

Basic information

Region (hg38): 5:36151988-36196849

Links

ENSG00000145604 ∙ NCBI:6502 ∙ OMIM:601436 ∙ HGNC:10901 ∙ Uniprot:Q13309 ∙ 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 SKP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SKP2 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			10			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			8	7	1	16
Total	0	0	18	7	1

Variants in SKP2

This is a list of pathogenic ClinVar variants found in the SKP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-36152794-A-C		not specified	Uncertain significance (May 24, 2024)
5-36152839-C-T		not specified	Uncertain significance (Aug 02, 2023)
5-36153033-A-G		not specified	Uncertain significance (May 31, 2024)
5-36153035-C-G		not specified	Uncertain significance (May 14, 2024)
5-36168320-C-T		not specified	Uncertain significance (Aug 02, 2021)
5-36170397-G-T		not specified	Uncertain significance (Dec 28, 2022)
5-36177202-A-C		not specified	Uncertain significance (Nov 08, 2022)
5-36181832-T-C		not specified	Uncertain significance (Sep 21, 2023)
5-36181888-C-G		not specified	Uncertain significance (May 24, 2023)
5-36182022-T-A		not specified	Uncertain significance (Sep 16, 2021)
5-36182027-T-A		not specified	Uncertain significance (Apr 12, 2023)
5-36183856-G-A		not specified	Uncertain significance (Jan 09, 2024)
5-36183970-G-T		not specified	Uncertain significance (Jan 06, 2023)
5-36195163-G-A		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Uncertain significance (Jun 29, 2023)
5-36195168-A-C			Likely benign (Jan 01, 2024)
5-36195177-T-A		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
5-36195196-G-A		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Uncertain significance (Nov 08, 2022)
5-36195203-T-C		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Uncertain significance (Jan 11, 2024)
5-36195225-A-C		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Likely benign (Feb 11, 2023)
5-36195237-A-G		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Likely benign (Sep 26, 2023)
5-36195238-T-C		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Uncertain significance (Jan 30, 2023)
5-36195244-A-G		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Uncertain significance (Jan 24, 2023)
5-36195248-T-C		Progressive encephalopathy with leukodystrophy due to DECR deficiency • NADK2-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 29, 2024)
5-36195252-G-C		Progressive encephalopathy with leukodystrophy due to DECR deficiency	Likely benign (Aug 23, 2022)
5-36195255-A-G			Likely benign (Jul 20, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SKP2	protein_coding	protein_coding	ENST00000274255	10	32331

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.960	0.0396	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	148	232	0.639	0.0000120	2753
Missense in Polyphen		21	54.299	0.38675		732
Synonymous	0.578	87	94.1	0.924	0.00000482	854
Loss of Function	3.90	3	23.3	0.129	0.00000127	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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 involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration. {ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16103164, ECO:0000269|PubMed:16262255, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:22770219}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Cell cycle - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Cell Cycle;Retinoblastoma (RB) in Cancer;Imatinib and Chronic Myeloid Leukemia;regulation of p27 phosphorylation during cell cycle progression;Transcriptional regulation by RUNX2;Notch;Gene expression (Transcription);e2f1 destruction pathway;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;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 ;Antigen processing: Ubiquitination & Proteasome degradation;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;Orc1 removal from chromatin;DNA Replication;Switching of origins to a post-replicative state;Class I MHC mediated antigen processing & presentation;Synthesis of DNA;S Phase;Neddylation;Ub-specific processing proteases;Deubiquitination;G1/S Transition;C-MYC pathway;Notch signaling pathway;Cell Cycle;Cell Cycle, Mitotic;FOXM1 transcription factor network;FoxO family signaling;Regulation of retinoblastoma protein;p53 pathway;Regulation of RUNX2 expression and activity (Consensus)

Recessive Scores

• pRec: 0.228

Intolerance Scores

• loftool: 0.474
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.845
• hipred: Y
• hipred_score: 0.739
• ghis: 0.684

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.818

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Skp2
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; reproductive system phenotype; liver/biliary system phenotype; renal/urinary system phenotype; immune system phenotype

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;G2/M transition of mitotic cell cycle;protein polyubiquitination;cell population proliferation;viral process;protein deubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;positive regulation of intracellular estrogen receptor signaling pathway;regulation of apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;innate immune response;positive regulation of smooth muscle cell proliferation;defense response to virus;regulation of cell cycle;protein K48-linked ubiquitination;cellular response to cell-matrix adhesion;positive regulation of protein polyubiquitination
• Cellular component: nucleus;nucleoplasm;nucleolus;cytosol;SCF ubiquitin ligase complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;identical protein binding;ubiquitin protein ligase activity