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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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UHMK1
U2AF homology motif kinase 1
Chromosome 1 · 1q23.3
NCBI Gene: 127933Ensembl: ENSG00000152332.17HGNC: HGNC:19683UniProt: Q8TAS1
36PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusnucleoplasmprotein bindingATP bindingneuroendocrine neoplasmRare genetic intellectual disability with developmental anomalyneurodegenerative diseaselung adenocarcinoma
✦AI Summary

UHMK1 (U2AF homology motif kinase 1) is a serine/threonine kinase containing a U2AF homology motif that functions in multiple cellular processes. As a splicing regulatory kinase, UHMK1 interacts with splicing factors SF1 and SF3B1 and phosphorylates over 117 proteins involved in spliceosome assembly and mRNA processing, affecting more than 270 alternative splicing events 1. In cell cycle regulation, UHMK1 phosphorylates CDKN1B/p27Kip1 to control G1 phase progression. Beyond splicing, UHMK1 functions as a potent oncogene across multiple cancer types. In colorectal cancer, UHMK1 promotes proliferation and chemoresistance through IL-6/STAT3 signaling via a positive feedback loop 2. In gastric cancer, UHMK1 enhances de novo purine synthesis by phosphorylating NCOA3, activating the ATF4 transcription factor 3. In lung adenocarcinoma, UHMK1 activates the PI3K/AKT/mTOR pathway 4, while in hepatocellular carcinoma, YAP-induced UHMK1 promotes MYBL2 nuclear enrichment and cell cycle gene expression 5. High UHMK1 expression in oral squamous cell carcinoma correlates with advanced TNM stage, lymph node metastasis, and poor survival 6. Genetically, UHMK1 variants show association with schizophrenia susceptibility 7, though expression levels appear unchanged in the disease 8.

Sources cited
1
UHMK1 is a splicing regulatory kinase that interacts with SF1 and SF3B1, phosphorylates splicing factors, and affects alternative splicing events
PMID: 36803961
2
UHMK1 promotes colorectal cancer proliferation and chemoresistance through IL-6/STAT3 signaling via positive feedback regulation
PMID: 35501324
3
UHMK1 promotes gastric cancer by phosphorylating NCOA3 to activate ATF4 and enhance de novo purine synthesis
PMID: 31975428
4
UHMK1 promotes lung adenocarcinoma through the PI3K/AKT/mTOR signaling pathway
PMID: 36919755
5
YAP induces UHMK1 expression, which promotes hepatocellular carcinoma proliferation through MYBL2 nuclear enrichment and cell cycle gene expression
PMID: 30936457
6
High UHMK1 expression in oral squamous cell carcinoma is associated with advanced TNM stage, lymph node metastasis, and poor survival
PMID: 39129074
7
UHMK1 genetic variants show association with schizophrenia susceptibility on chromosome 1q23.3
PMID: 18414510
8
UHMK1 is expressed in neurons with nuclear and cytoplasmic localization, but expression levels are not altered in schizophrenia
PMID: 19747464
Disease Associationsⓘ20
neuroendocrine neoplasmOpen Targets
0.27Weak
Rare genetic intellectual disability with developmental anomalyOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.24Weak
lung adenocarcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
schizophreniaOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
Combined hyperlipidemiaOpen Targets
0.04Suggestive
Parkinson diseaseOpen Targets
0.04Suggestive
hypertriglyceridemia 2Open Targets
0.04Suggestive
hyperlipidemia due to hepatic triglyceride lipase deficiencyOpen Targets
0.03Suggestive
oral squamous cell carcinomaOpen Targets
0.03Suggestive
heart diseaseOpen Targets
0.03Suggestive
leukemiaOpen Targets
0.02Suggestive
immune system diseaseOpen Targets
0.02Suggestive
knee fractureOpen Targets
0.02Suggestive
cervical squamous cell carcinomaOpen Targets
0.02Suggestive
Pathogenic Variants1
NM_175866.5(UHMK1):c.1214C>T (p.Pro405Leu)Likely pathogenic
Cerebral visual impairment and intellectual disability
★☆☆☆2015→ Residue 405
View on ClinVar ↗
Related Genes
STMN1Protein interaction82%KCND3Protein interaction70%KCNIP2Protein interaction70%KCNIP1Protein interaction70%KCNIP4Protein interaction70%CDKL4Shared pathway20%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
83%
Liver
52%
Lung
39%
Heart
37%
Ovary
23%
Gene Interaction Network
Click a node to explore
UHMK1STMN1KCND3KCNIP2KCNIP1KCNIP4CDKL4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8TAS1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.62LoF Tolerant
pLIⓘ
0.26Tolerant
Observed/Expected LoF0.41 [0.28–0.62]
RankingsWhere UHMK1 stands among ~20K protein-coding genes
  • #10,893of 20,598
    Most Researched36
  • #5,208of 5,498
    Most Pathogenic Variants1
  • #4,355of 17,882
    Most Constrained (LOEUF)0.62 · top quartile
Genes detectedUHMK1
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
UHMK1 aids colorectal cancer cell proliferation and chemoresistance through augmenting IL-6/STAT3 signaling.
PMID: 35501324
Cell Death Dis · 2022
1.00
2
Expression and clinical significance of U2AF homology motif kinase 1 in oral squamous cell carcinoma.
PMID: 39129074
Oral Surg Oral Med Oral Pathol Oral Radiol · 2024
0.90
3
UHMK1 promotes gastric cancer progression through reprogramming nucleotide metabolism.
PMID: 31975428
EMBO J · 2020
0.80
4
Confirmation of the genetic association between the U2AF homology motif (UHM) kinase 1 (UHMK1) gene and schizophrenia on chromosome 1q23.3.
PMID: 18414510
Eur J Hum Genet · 2008
0.70
5
UHMK1 is a novel splicing regulatory kinase.
PMID: 36803961
J Biol Chem · 2023
0.60