Incidental Mutation 'P0018:Sufu'
ID 7639
Institutional Source Beutler Lab
Gene Symbol Sufu
Ensembl Gene ENSMUSG00000025231
Gene Name SUFU negative regulator of hedgehog signaling
Synonyms b2b273Clo, 2810026F04Rik, Su(Fu)
MMRRC Submission 038271-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # P0018 (G1)
Quality Score
Status Validated
Chromosome 19
Chromosomal Location 46385335-46477243 bp(+) (GRCm39)
Type of Mutation splice site
DNA Base Change (assembly) A to G at 46463933 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000113073 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000039922] [ENSMUST00000111867] [ENSMUST00000118440]
AlphaFold Q9Z0P7
Predicted Effect probably benign
Transcript: ENSMUST00000039922
SMART Domains Protein: ENSMUSP00000049109
Gene: ENSMUSG00000025231

DomainStartEndE-ValueType
low complexity region 9 34 N/A INTRINSIC
Pfam:SUFU 63 242 2.9e-38 PFAM
Pfam:SUFU_C 252 473 1.6e-99 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000111867
SMART Domains Protein: ENSMUSP00000107498
Gene: ENSMUSG00000025231

DomainStartEndE-ValueType
low complexity region 9 34 N/A INTRINSIC
Pfam:SUFU 64 241 4.9e-54 PFAM
Pfam:SUFU_C 254 474 2.3e-89 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000118440
SMART Domains Protein: ENSMUSP00000113073
Gene: ENSMUSG00000025231

DomainStartEndE-ValueType
low complexity region 9 34 N/A INTRINSIC
Pfam:SUFU 63 242 3.2e-38 PFAM
Pfam:SUFU_C 252 436 9.8e-78 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000123252
Coding Region Coverage
  • 1x: 83.8%
  • 3x: 77.4%
  • 10x: 57.9%
  • 20x: 38.3%
Validation Efficiency 72% (76/106)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
PHENOTYPE: Targeted disruption results in mid-gestation lethality, embryonic growth retardation, incomplete embryo turning, open neural tube, abnormal somite development, left-right asymmetry defects resulting in cardiac looping, and hemorrhage in the diencephalon. [provided by MGI curators]
Allele List at MGI

All alleles(32) : Targeted(7) Gene trapped(25)
Other mutations in this stock
Total: 14 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
AAdacl4fm3 A T 4: 144,429,767 (GRCm39) D407E probably benign Het
Brip1 C T 11: 85,999,694 (GRCm39) V763I possibly damaging Het
Cspg4b A G 13: 113,504,040 (GRCm39) D1723G possibly damaging Het
Cxxc1 C T 18: 74,353,992 (GRCm39) R593C probably damaging Het
Erbb4 T A 1: 68,110,835 (GRCm39) M993L probably benign Het
Ftsj3 C A 11: 106,145,634 (GRCm39) M66I possibly damaging Het
Galnt2 T A 8: 125,063,350 (GRCm39) Y357N probably damaging Het
Hgsnat C T 8: 26,458,382 (GRCm39) probably benign Het
Katna1 A T 10: 7,617,223 (GRCm39) T72S probably damaging Het
Nell1 A G 7: 49,770,439 (GRCm39) D166G probably damaging Het
Nlgn1 G T 3: 25,490,741 (GRCm39) P329T probably damaging Het
Pclo A T 5: 14,727,735 (GRCm39) probably benign Het
Robo2 T C 16: 73,843,694 (GRCm39) I174V possibly damaging Het
Tmub1 C A 5: 24,651,755 (GRCm39) A55S possibly damaging Het
Other mutations in Sufu
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01322:Sufu APN 19 46,439,382 (GRCm39) missense probably damaging 1.00
IGL01613:Sufu APN 19 46,464,059 (GRCm39) missense probably damaging 1.00
IGL01652:Sufu APN 19 46,464,059 (GRCm39) missense probably damaging 1.00
IGL02420:Sufu APN 19 46,413,481 (GRCm39) missense probably damaging 1.00
IGL02501:Sufu APN 19 46,439,349 (GRCm39) missense probably benign 0.04
IGL02984:Sufu UTSW 19 46,462,038 (GRCm39) missense probably benign
R0172:Sufu UTSW 19 46,385,563 (GRCm39) missense possibly damaging 0.86
R0280:Sufu UTSW 19 46,439,112 (GRCm39) splice site probably benign
R1175:Sufu UTSW 19 46,389,703 (GRCm39) splice site probably null
R1295:Sufu UTSW 19 46,443,159 (GRCm39) splice site probably benign
R1296:Sufu UTSW 19 46,443,159 (GRCm39) splice site probably benign
R1420:Sufu UTSW 19 46,385,623 (GRCm39) missense probably benign 0.36
R1846:Sufu UTSW 19 46,439,386 (GRCm39) missense possibly damaging 0.47
R2061:Sufu UTSW 19 46,385,651 (GRCm39) missense probably damaging 1.00
R4082:Sufu UTSW 19 46,413,541 (GRCm39) missense probably damaging 0.99
R4151:Sufu UTSW 19 46,438,411 (GRCm39) critical splice donor site probably null
R4744:Sufu UTSW 19 46,472,069 (GRCm39) missense possibly damaging 0.78
R4751:Sufu UTSW 19 46,472,088 (GRCm39) missense probably benign 0.01
R4959:Sufu UTSW 19 46,463,991 (GRCm39) missense possibly damaging 0.58
R4973:Sufu UTSW 19 46,463,991 (GRCm39) missense possibly damaging 0.58
R5221:Sufu UTSW 19 46,439,404 (GRCm39) critical splice donor site probably null
R5890:Sufu UTSW 19 46,443,172 (GRCm39) critical splice acceptor site probably null
R6030:Sufu UTSW 19 46,463,978 (GRCm39) missense probably damaging 0.99
R6030:Sufu UTSW 19 46,463,978 (GRCm39) missense probably damaging 0.99
R6226:Sufu UTSW 19 46,462,093 (GRCm39) missense probably damaging 1.00
R6233:Sufu UTSW 19 46,464,071 (GRCm39) missense probably damaging 1.00
R6811:Sufu UTSW 19 46,438,317 (GRCm39) missense probably damaging 1.00
R6923:Sufu UTSW 19 46,439,405 (GRCm39) splice site probably null
R7095:Sufu UTSW 19 46,464,027 (GRCm39) missense probably damaging 1.00
R7223:Sufu UTSW 19 46,441,716 (GRCm39) missense possibly damaging 0.82
R7390:Sufu UTSW 19 46,439,108 (GRCm39) splice site probably null
R8190:Sufu UTSW 19 46,389,636 (GRCm39) nonsense probably null
R9424:Sufu UTSW 19 46,474,320 (GRCm39) nonsense probably null
R9433:Sufu UTSW 19 46,385,532 (GRCm39) start gained probably benign
R9550:Sufu UTSW 19 46,385,675 (GRCm39) missense probably damaging 1.00
R9594:Sufu UTSW 19 46,385,674 (GRCm39) missense probably damaging 1.00
Protein Function and Prediction

Suppressor of fused (Sufu) is a negative regulator of the Sonic hedgehog/Patched signaling pathway [(1-3); reviewed in (4)].  It is proposed that Sufu functions to sequester glioma-associated oncogene (GLI1), a marker for sonic hedgehog activity, in the cytoplasm (3) and/or to act as a GLI1 corepressor.
Expression/Localization

Northern blot found that SUFU is ubiquitously expressed; in situ hybridization detected expression throughout midgestation in the neural tube and, later, in the neural tube's brain and spinal cord derivatives (3).
Background

Mutations in SUFU are linked to desmoplastic medulloblastoma [OMIM: #155255; (5-7)] and susceptibility to familial meningioma [OMIM: #607174; (8)]. Medulloblastoma is the most common brain tumor in children; meningiomas are, in general, slowly growing benign tumors derived from the arachnoidal cap cells of the leptomeninges, the soft coverings of the brain and spinal cord.

Sufutm1Aeb/tm1Aeb; MGI: 3512046

either: 129S1/Sv-Sufutm1Aeb or (involves: 129S1/Sv * C57BL/6)

Homozygous mice do not survive past E10.5 (1).  These mice have abnormal developmental patterning, dorsal-ventral axis patterning, somite development, incomplete embryo turning, descending aorta dilation, brain aneurysm, and abnormal direction of heart looping (1). 

Sufutm1Rto/tm1Rto; MGI:3619046

involves: 129X1/SvJ * C57BL/6

Homozygotes die around E9.5 and exhibit abnormal neural tube morphology and development, abnormal floor plate morphology, open neural tube, and abnormal brain development (2).
References
Posted On 2012-10-29
Science Writer Anne Murray