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Symbol SUFU contributors: shn/npt - updated : 17-11-2017
HGNC name suppressor of fused homolog (Drosophila)
HGNC id 16466
Corresponding disease
JBTS32 Joubert syndrome 32
MDB medulloblastoma, SUFU related
NBCCS3 nevoid basal cell carcinoma syndrome 3
Location 10q24.32      Physical location : 104.263.718 - 104.393.214
Synonym name likely ortholog of mouse suppressor of fused homolog (Drosophila)
Synonym symbol(s) SUFUH, SUFUXL, PRO1280, JBTS32, PRO1280H
TYPE functioning gene
STRUCTURE 129.49 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D10S1710 - D10S1240 - SUFU - D10S1697 - D10S1267 - qter
TRANSCRIPTS type messenger
  • encodes a component of the Sonic hedgehog signaling pathway
  • miR378 targets sequence in the 3-prime UTRs of SUFU transcript and miR378 downregulates its expression
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1900 - 433 - 2001 1155703
  • SUFUv2
  • 12 - 4894 - 484 - 2001 1155703
  • SUFUv1
  • 10 - 2673 - 481 - 2001 1155703
    13 - - - - detected in Pancreatic ductal adenocarcinoma (PDAC) tissue 2016 27840902
  • sequence of the new protein-coding exon was the same as a fragment of intron between exon 10 and 11 of SUFUv1
  • SUFU isoform N
  • novel transcript variant of SUFU which can be transcribed and translated into corresponding protein and its transcription is related with metastasis of lymph nodes in PDAC
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon lowly
     liver   highly
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly
    Reproductivefemale systemplacenta  highly
     female systemovary  highly
     male systemprostate  highly
     male systemtestis  highly
    Respiratorylung   highly
    Urinarykidney   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    Text highly expressed in osteoblasts in the perichondrium during human embryonic bone formation
  • a high-scoring PEST domain
  • a N-terminal globular domain
  • four consensus protein kinase A (PKA) recognition sites
    interspecies ortholog to Sufu, Mus musculus
    homolog to Drosophila (sufu)
    ortholog to SUFU, Pan troglodytes
    ortholog to Sufu, Rattus norvegicus
    ortholog to sufu, danio rerio
    FAMILY SUFU family
    CATEGORY adaptor , regulatory , transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
  • GLIS3 and SUFU co-localize to the nucleus
  • on a cellular level, endogenous SUFU can mainly be detected in the cytoplasm and the nucleus
  • basic FUNCTION
  • is a key negative regulator in the vertebrate Hedgehog signaling pathway
  • inhibiting the GLI-1 transcriptal activator in Hedgehog signaling pathway and hegative regulator of HH signaling
  • serving as an adaptor linking GLI to the SLIMB-dependent proteasomal degradation pathway
  • inhibiting osteogenic differentiation in response to signalling from sonic Hedgehog
  • controls protein levels of full-length GLI1, GLI2, GLI3 transcription factors, thus affecting the production of GLI activators and repressors essential for graded Hh responses
  • predisposing to medulloblastoma by modulating the SHH signaling pathway
  • prevent the nuclear transportation of GLIs (GLI1, GLI2, GLI3), as well as to promote their processing
  • Sufu degradation through the ubiquitin–proteasome pathway is promoted by Sonic hedgehog (Shh)
  • controls cerebellar patterning and cell differentiation in a GLI3 repressor-dependent manner
  • potential role for SUFU in the modulation of different aspects of the GLIS3 signaling pathway, including the transcriptional regulation of target genes and protein stability
  • major negative regulator of the Hh-signaling pathway
  • SUFU and KIF7 are crucial components in the regulation of GLI2 localization and activity, illustrating their overlapping functions in skin development and tumor suppression
  • essential repressor of SHH signaling pathway
  • controlling protein levels of all three GLI genes by SUFU is a conserved mechanism to modulate HH responses albeit via distinct pathways
  • plays a conservative role in the regulation of the GLI transcription factors within the Hedgehog (Hh) signaling pathway
  • controls cerebellar neuronal differentiation in a manner modulated by GLI3 repressor and FGF19
  • tissue development is differentially affected in response to the reduced SUFU levels, providing novel insight regarding the requirements of different levels of SUFU for proper organogenesis
  • the canonical role of SUFU as an inhibitor of SHH signaling is conserved at later stages of corticogenesis and SUFU plays a crucial role in regulating neuronal number by controlling the cell cycle dynamics of intermediate progenitor (IP) cells in the embryonic neocortex
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, degradation
  • skeletal development
  • nucleocytoplasmic transport of GLI-1
    Hedgehog signalling pathway
    a component
  • MYCBP forms a complex with GLI and SUFU without HH stimulation but remains inactive
    small molecule
  • zinc-finger transcription factor Gli
  • GLI1 transcriptional activator
  • GLI2 and GLI3
  • SLIMB, F-box containing protein
  • interacting with ULK3 through its kinase domain (KD)
  • interacting with SPOP and GLI1, GLI2, GLI3 (SUFU regulates GLI protein levels by antagonizing the activity of SPOP, a conserved GLI-degrading factor) (physically interacts with SUFU, and the ULK3-SUFU complex is sensitive to SHH signaling)
  • interacting with GLIS3 (GLIS3 promoted the nuclear accumulation of SUFU)
  • RAB23 directly associates with SUFU and inhibits GLI1 function in a SUFU-dependent manner
  • PTHLH regulates chondrocyte differentiation and GLI activity in a SUFU-dependent manner, with SUFU acting as a molecular switch in its regulation of differentiation
  • KIF7 is required to establish high intracellular GLI activity by antagonizing the SUFU-inhibition of GLI2
  • RIOK3 is a novel modulator of SUFU subcellular distribution
  • TTC26 is necessary for efficient coupling between the accumulation of GLI at the ciliary tip and its dissociation from SUFU
  • SUFU recruits GATAD2B to block GLI-mediated HH target gene expression
  • perturbations of SUFU and KIF7 affect GLI activity and recapitulate the full spectrum of vertebrate limb defects, ranging from severe truncation to polydactyly
  • SUFU is involved in the genetic network that restricts the posterior expression of GLI2/3/HAND2 and GREMLIN/FGF in limb bud patterning
  • NEK2 is found to stabilize SUFU at least partly depending on its kinase activity, thereby triggering phosphorylation of the SUFU protein
  • RUSC1 and RUSC2 interact with SUFU and restrict the response of cells to HH signaling
  • NEK2 stabilizes SUFU through impairing ubiquitin/proteasome degradation of SUFU
  • BCL2 proteins directly promote SUFU turnover, inhibit SUFU-GLI interaction, and induce the expression of the GLI target genes BCL2, MCL1 and BCL2L1
  • cell & other
    Other factors modulating the nucleo-cytoplasmic distribution of SUFU impact on the normal function of this tumor suppressing protein
    corresponding disease(s) MDB , NBCCS3 , JBTS32
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in medulloblastoma and skin tumor
    tumoral somatic mutation      
    in basal cell carcinoma (BCC) of the skin
    tumoral germinal mutation      
    predispose to meningiomas, particularly to multiple meningiomas
    constitutional germinal mutation      
    can result in neural tube defects
  • associated with cancer-predisposing syndromes: basal cell nevus syndrome
  • to NTDs (Neural tube defects) and encephalocele
  • Variant & Polymorphism other
  • SUFU mutations predispose to meningiomas in addition to medulloblastomas
  • rs10786691 A>G polymorphism may be a potential risk factor for NTDs and encephalocele
  • Candidate gene
    Therapy target
  • mouse deleted for Sufu gene led to lethality at embryonic day 9.5 with cephalic and neural tube defects. Mice heterozygous for Sufu deletion are normal and fertile but develope a skin phenotype with basaloid changes and jaw keratocysts (Svard et al, 2006)
  • mutant mice lacking Sufu show excessive pathway activity and die as embryos with patterning defects