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)
|
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
Domain | Start | End | E-Value | Type |
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
Domain | Start | End | E-Value | Type |
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
Domain | Start | End | E-Value | Type |
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
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
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 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
1. Cooper, A. F., Yu, K. P., Brueckner, M., Brailey, L. L., Johnson, L., McGrath, J. M., and Bale, A. E. (2005) Cardiac and CNS Defects in a Mouse with Targeted Disruption of Suppressor of Fused. Development. 132, 4407-4417.
2. Svard, J., Heby-Henricson, K., Persson-Lek, M., Rozell, B., Lauth, M., Bergstrom, A., Ericson, J., Toftgard, R., and Teglund, S. (2006) Genetic Elimination of Suppressor of Fused Reveals an Essential Repressor Function in the Mammalian Hedgehog Signaling Pathway. Dev Cell. 10, 187-197.
3. Kogerman, P., Grimm, T., Kogerman, L., Krause, D., Unden, A. B., Sandstedt, B., Toftgard, R., and Zaphiropoulos, P. G. (1999) Mammalian Suppressor-of-Fused Modulates Nuclear-Cytoplasmic Shuttling of Gli-1. Nat Cell Biol. 1, 312-319.
5. Bayani, J., Zielenska, M., Marrano, P., Kwan Ng, Y., Taylor, M. D., Jay, V., Rutka, J. T., and Squire, J. A. (2000) Molecular Cytogenetic Analysis of Medulloblastomas and Supratentorial Primitive Neuroectodermal Tumors by using Conventional Banding, Comparative Genomic Hybridization, and Spectral Karyotyping. J Neurosurg. 93, 437-448.
6. Taylor, M. D., Liu, L., Raffel, C., Hui, C. C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., and Hogg, D. (2002) Mutations in SUFU Predispose to Medulloblastoma. Nat Genet. 31, 306-310.
7. Brugieres, L., Pierron, G., Chompret, A., Paillerets, B. B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., and Delattre, O. (2010) Incomplete Penetrance of the Predisposition to Medulloblastoma Associated with Germ-Line SUFU Mutations. J Med Genet. 47, 142-144.
8. Aavikko, M., Li, S. P., Saarinen, S., Alhopuro, P., Kaasinen, E., Morgunova, E., Li, Y., Vesanen, K., Smith, M. J., Evans, D. G., Poyhonen, M., Kiuru, A., Auvinen, A., Aaltonen, L. A., Taipale, J., and Vahteristo, P. (2012) Loss of SUFU Function in Familial Multiple Meningioma. Am J Hum Genet. 91, 520-526.
|
Posted On |
2012-10-29 |
Science Writer |
Anne Murray |