SKP1

Chr 5

S-phase kinase associated protein 1

Also known as: EMC19, OCP-II, OCP2, SKP1A, TCEB1L, p19A

NCBI Gene: 6500ENSG00000113558UniProt: P63208

This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. SCF complexes are involved in the regulated ubiquitination of specific protein substrates, which targets them for degradation by the proteosome. Specific F-box proteins recognize different target protein(s), and many specific SCF substrates have been identified including regulators of cell cycle progression and development. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Jul 2008]

26
ClinVar variants
16
Pathogenic / LP
0.37
pLI score
0
Active trials
Clinical Summary— SKP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 9 VUS of 26 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.373
Z-score 2.17
OE 0.22 (0.09–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.66Z-score
OE missense 0.19 (0.13–0.29)
16 obs / 85.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.09–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.19 (0.13–0.29)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 2 / 9.0Missense obs/exp: 16 / 85.1Syn Z: -0.23

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS9
Likely Benign1
15
Pathogenic
1
Likely Pathogenic
9
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
7
2
0
9
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0719026

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SKP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo variants in FBXO11 cause a syndromic form of intellectual disability with behavioral problems and dysmorphisms.
Jansen S et al.·Eur J Hum Genet
2019
Clinical significance of FBXW7 loss of function in human cancers.
Fan J et al.·Mol Cancer
2022Review
Molecular insights and clinical implications for the tumor suppressor role of SCF(FBXW7) E3 ubiquitin ligase.
Qi Y et al.·Biochim Biophys Acta Rev Cancer
2024Review
FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors.
Nguyen-Dien GT et al.·EMBO J
2023
Hypoxic and Acidic Tumor Microenvironment-Driven AVL9 Promotes Chemoresistance of Pancreatic Ductal Adenocarcinoma via the AVL9-IκBα-SKP1 Complex.
Ding J et al.·Gastroenterology
2025
Cullin-associated and neddylation-dissociated 1 regulate reprogramming of lipid metabolism through SKP1-Cullin-1-F-box(FBXO11) -mediated heterogeneous nuclear ribonucleoprotein A2/B1 ubiquitination and promote hepatocellular carcinoma.
Zhang H et al.·Clin Transl Med
2023
Skp1: Implications in cancer and SCF-oriented anti-cancer drug discovery.
Hussain M et al.·Pharmacol Res
2016Review
SCF ubiquitin ligase-targeted therapies.
Skaar JR et al.·Nat Rev Drug Discov
2014Review
The characteristics of FBXO7 and its role in human diseases.
Zhong Y et al.·Gene
2023Review
TBL1X: At the crossroads of transcriptional and posttranscriptional regulation.
Pray BA et al.·Exp Hematol
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Investigating the potential causal link between BPA and ovarian carcinogenesis: a network toxicology and mendelian randomization study on the CTRC/PRDX1/SKP1 pathway.
Shi Z et al.·J Ovarian Res
2025🔓 Open Access
The negative regulated immune mechanism of Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase-mediated HOS15-dependent responses in banana.
Chen X et al.·Plant Cell Rep
2025Functional
High glucose induces hippocampal neuron impairment through the SKP1/COX7C pathway: A potential mechanism for perimenopausal depression.
Wang Z et al.·Acta Pharm Sin B
2025🔓 Open AccessFunctional
IBSP mediates fibroblast malignant behaviors in hypertrophic scars via interacting with SKP1.
Zhang Y et al.·Burns
2025
Degradation of AtSRC2 by SKP1/BTB/POZ domain effectors in Heterodera schachtii inhibits RBOHF via ROS and enhances infection.
Yao K et al.·New Phytol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools