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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SUGP1
SURP and G-patch domain containing 1
Chromosome 19 · 19p13.11
NCBI Gene: 57794Ensembl: ENSG00000105705.17HGNC: HGNC:18643UniProt: Q8IWZ8
84PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingprotein bindingnucleoplasmnucleusneurodegenerative diseasedengue diseasecirrhosis of livertype 2 diabetes mellitus
✦AI Summary

SUGP1 (SURP and G-patch domain containing 1) is a G-patch protein that plays a critical role in pre-mRNA splicing quality control. Functionally, SUGP1 acts as a regulatory factor that activates the DExH-box helicase DHX15 to promote splicing fidelity by triggering early spliceosome disassembly in response to kinetic blocks 1. SUGP1 specifically recruits DHX15 to suppress suboptimal introns with weak splice sites and cryptic introns, preventing their incorporation into mature transcripts 2. The protein contains a U2AF ligand motif (ULM) domain essential for DHX15 interaction 2. Clinically, SUGP1 dysfunction is implicated in cancer pathogenesis. Loss of SUGP1 recapitulates nearly all splicing defects induced by oncogenic SF3B1 hotspot mutations, the most frequently mutated splicing factor in cancer 3. SF3B1 mutations disrupt SUGP1 interaction, leading to aberrant 3' splice site usage and widespread missplicing 4. Additionally, SUGP1 genetic variants (rs10401969) associate with alcohol-related cirrhosis risk when combined with other genetic factors and diabetes status 5. The discovery that SUGP1 loss drives SF3B1-mutant missplicing establishes SUGP1 as a fundamental regulator of splicing accuracy and a potential therapeutic target in SF3B1-mutant malignancies.

Sources cited
1
SUGP1 G-patch domain functions in splicing fidelity by triggering early spliceosome disassembly; interacts with DHX15/hPrp43
PMID: 37402368
2
SUGP1 activates DHX15's splicing quality control function; interaction requires DHX15 ATPase activity and SUGP1's ULM domain
PMID: 37805921
3
SUGP1 loss reproduces almost all splicing defects induced by SF3B1 hotspot mutations in cancer
PMID: 40714635
4
SF3B1 K700E mutations disrupt SF3B1 interaction with SUGP1 and induce aberrant U2/branch site recognition
PMID: 40138349
5
SUGP1 genetic variant rs10401969 associates with alcohol-related cirrhosis risk in combination with diabetes and other genetic factors
PMID: 34656649
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.38Weak
dengue diseaseOpen Targets
0.37Weak
cirrhosis of liverOpen Targets
0.24Weak
type 2 diabetes mellitusOpen Targets
0.18Weak
bipolar disorderOpen Targets
0.18Weak
diabetes mellitusOpen Targets
0.18Weak
metabolic syndromeOpen Targets
0.18Weak
obesityOpen Targets
0.16Weak
diabetic ketoacidosisOpen Targets
0.15Weak
Abnormality of the skeletal systemOpen Targets
0.15Weak
hepatocellular carcinomaOpen Targets
0.14Weak
HypercholesterolemiaOpen Targets
0.14Weak
non-alcoholic fatty liver diseaseOpen Targets
0.13Weak
liver diseaseOpen Targets
0.13Weak
bipolar I disorderOpen Targets
0.12Weak
Abnormality of refractionOpen Targets
0.12Weak
ulcerative colitisOpen Targets
0.12Weak
cancerOpen Targets
0.12Weak
hyperlipidemiaOpen Targets
0.12Weak
metabolic diseaseOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RBMS2Shared pathway100%RTCAShared pathway100%ZRANB2Shared pathway100%SUGP2Shared pathway100%U2SURPShared pathway100%TRMT2AShared pathway100%
Tissue Expression6 tissues
Liver
100%
Heart
83%
Ovary
79%
Bone Marrow
78%
Lung
73%
Brain
69%
Gene Interaction Network
Click a node to explore
SUGP1RBMS2RTCAZRANB2SUGP2U2SURPTRMT2A
PROTEIN STRUCTURE
Preparing viewer…
PDB8EJM · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.60LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.45 [0.34–0.60]
RankingsWhere SUGP1 stands among ~20K protein-coding genes
  • #5,701of 20,598
    Most Researched84
  • #4,138of 17,882
    Most Constrained (LOEUF)0.60 · top quartile
Genes detectedSUGP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Molecular impact of mutations in RNA splicing factors in cancer.
PMID: 39146933
Mol Cell · 2024
1.00
2
Targeted high-throughput mutagenesis of the human spliceosome reveals its in vivo operating principles.
PMID: 37402368
Mol Cell · 2023
0.90
3
GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies.
PMID: 38688280
Mol Cell · 2024
0.80
4
Association of the
PMID: 32568739
Aging (Albany NY) · 2020
0.70
5
A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.
PMID: 34656649
J Hepatol · 2022
0.60