Incidental Mutation 'P0024:Scmh1'
ID |
7783 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Scmh1
|
Ensembl Gene |
ENSMUSG00000000085 |
Gene Name |
sex comb on midleg homolog 1 |
Synonyms |
Scml3 |
MMRRC Submission |
038277-MU
|
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
P0024 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
4 |
Chromosomal Location |
120262478-120387383 bp(+) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 120335231 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Phenylalanine to Leucine
at position 139
(F139L)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000101908
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000000087]
[ENSMUST00000064991]
[ENSMUST00000106298]
[ENSMUST00000106301]
|
AlphaFold |
Q8K214 |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000000087
AA Change: F139L
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000000087 Gene: ENSMUSG00000000085 AA Change: F139L
Domain | Start | End | E-Value | Type |
MBT
|
28 |
126 |
2.47e-48 |
SMART |
MBT
|
134 |
235 |
1.36e-45 |
SMART |
low complexity region
|
268 |
285 |
N/A |
INTRINSIC |
low complexity region
|
301 |
340 |
N/A |
INTRINSIC |
Pfam:DUF3588
|
354 |
468 |
4.3e-50 |
PFAM |
SAM
|
594 |
662 |
1.8e-10 |
SMART |
|
Predicted Effect |
probably damaging
Transcript: ENSMUST00000064991
AA Change: F139L
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000069813 Gene: ENSMUSG00000000085 AA Change: F139L
Domain | Start | End | E-Value | Type |
MBT
|
28 |
126 |
2.47e-48 |
SMART |
MBT
|
134 |
235 |
1.36e-45 |
SMART |
low complexity region
|
268 |
285 |
N/A |
INTRINSIC |
low complexity region
|
301 |
340 |
N/A |
INTRINSIC |
Pfam:DUF3588
|
357 |
465 |
5.8e-39 |
PFAM |
SAM
|
594 |
662 |
1.57e-10 |
SMART |
|
Predicted Effect |
probably damaging
Transcript: ENSMUST00000106298
AA Change: F139L
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000101905 Gene: ENSMUSG00000000085 AA Change: F139L
Domain | Start | End | E-Value | Type |
MBT
|
28 |
126 |
2.47e-48 |
SMART |
MBT
|
134 |
235 |
1.36e-45 |
SMART |
low complexity region
|
268 |
285 |
N/A |
INTRINSIC |
low complexity region
|
301 |
340 |
N/A |
INTRINSIC |
Pfam:DUF3588
|
354 |
468 |
4.3e-50 |
PFAM |
SAM
|
594 |
662 |
1.8e-10 |
SMART |
|
Predicted Effect |
probably damaging
Transcript: ENSMUST00000106301
AA Change: F139L
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000101908 Gene: ENSMUSG00000000085 AA Change: F139L
Domain | Start | End | E-Value | Type |
MBT
|
28 |
126 |
2.47e-48 |
SMART |
MBT
|
134 |
235 |
1.36e-45 |
SMART |
low complexity region
|
268 |
285 |
N/A |
INTRINSIC |
low complexity region
|
301 |
340 |
N/A |
INTRINSIC |
Pfam:DUF3588
|
354 |
468 |
4.7e-50 |
PFAM |
SAM
|
594 |
662 |
1.57e-10 |
SMART |
|
Meta Mutation Damage Score |
0.8059 |
Coding Region Coverage |
- 1x: 71.8%
- 3x: 61.2%
- 10x: 33.0%
- 20x: 13.9%
|
Validation Efficiency |
80% (70/87) |
MGI Phenotype |
PHENOTYPE: Mice homozygous for an allele lacking the SPM domain exhibit partial penetrance of posterior vertebral transformations and male infertility with azoospermia and arrest of spermatogenesis. Mice homozygous for a knock-out allele exhibit abnormal hematopoiesis but normal fertility and skeleton. [provided by MGI curators]
|
Allele List at MGI |
All alleles(67) : Targeted(4) Gene trapped(63)
|
Other mutations in this stock |
Total: 3 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Cdca8 |
C |
T |
4: 124,820,457 (GRCm39) |
|
probably null |
Het |
Mef2a |
G |
A |
7: 66,945,322 (GRCm39) |
T20I |
probably damaging |
Het |
Zfp708 |
C |
A |
13: 67,218,984 (GRCm39) |
E247* |
probably null |
Het |
|
Other mutations in Scmh1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL01613:Scmh1
|
APN |
4 |
120,387,097 (GRCm39) |
utr 3 prime |
probably benign |
|
IGL01962:Scmh1
|
APN |
4 |
120,340,781 (GRCm39) |
splice site |
probably benign |
|
IGL02013:Scmh1
|
APN |
4 |
120,340,929 (GRCm39) |
missense |
possibly damaging |
0.77 |
IGL02081:Scmh1
|
APN |
4 |
120,372,275 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02223:Scmh1
|
APN |
4 |
120,372,416 (GRCm39) |
missense |
probably benign |
0.26 |
IGL02530:Scmh1
|
APN |
4 |
120,385,343 (GRCm39) |
splice site |
probably benign |
|
IGL02887:Scmh1
|
APN |
4 |
120,325,586 (GRCm39) |
missense |
probably damaging |
1.00 |
R0164:Scmh1
|
UTSW |
4 |
120,387,062 (GRCm39) |
unclassified |
probably benign |
|
R0164:Scmh1
|
UTSW |
4 |
120,387,062 (GRCm39) |
unclassified |
probably benign |
|
R0200:Scmh1
|
UTSW |
4 |
120,341,028 (GRCm39) |
missense |
probably damaging |
0.99 |
R1598:Scmh1
|
UTSW |
4 |
120,372,327 (GRCm39) |
missense |
possibly damaging |
0.83 |
R1624:Scmh1
|
UTSW |
4 |
120,386,425 (GRCm39) |
missense |
probably damaging |
1.00 |
R2276:Scmh1
|
UTSW |
4 |
120,340,869 (GRCm39) |
missense |
probably damaging |
1.00 |
R3734:Scmh1
|
UTSW |
4 |
120,335,277 (GRCm39) |
missense |
probably damaging |
1.00 |
R4167:Scmh1
|
UTSW |
4 |
120,386,473 (GRCm39) |
intron |
probably benign |
|
R4570:Scmh1
|
UTSW |
4 |
120,385,495 (GRCm39) |
missense |
probably damaging |
1.00 |
R5458:Scmh1
|
UTSW |
4 |
120,362,478 (GRCm39) |
unclassified |
probably benign |
|
R5564:Scmh1
|
UTSW |
4 |
120,325,575 (GRCm39) |
missense |
probably damaging |
1.00 |
R5700:Scmh1
|
UTSW |
4 |
120,374,143 (GRCm39) |
missense |
probably benign |
0.10 |
R5991:Scmh1
|
UTSW |
4 |
120,379,817 (GRCm39) |
missense |
probably benign |
|
R5999:Scmh1
|
UTSW |
4 |
120,362,712 (GRCm39) |
critical splice donor site |
probably null |
|
R7097:Scmh1
|
UTSW |
4 |
120,382,252 (GRCm39) |
missense |
probably benign |
|
R7432:Scmh1
|
UTSW |
4 |
120,386,353 (GRCm39) |
missense |
probably damaging |
1.00 |
R8327:Scmh1
|
UTSW |
4 |
120,379,699 (GRCm39) |
missense |
probably benign |
|
R8680:Scmh1
|
UTSW |
4 |
120,319,331 (GRCm39) |
missense |
probably benign |
|
R8745:Scmh1
|
UTSW |
4 |
120,362,559 (GRCm39) |
nonsense |
probably null |
|
R9018:Scmh1
|
UTSW |
4 |
120,362,514 (GRCm39) |
missense |
probably benign |
0.01 |
R9141:Scmh1
|
UTSW |
4 |
120,362,556 (GRCm39) |
missense |
probably benign |
0.00 |
R9283:Scmh1
|
UTSW |
4 |
120,319,337 (GRCm39) |
missense |
probably benign |
|
R9426:Scmh1
|
UTSW |
4 |
120,362,556 (GRCm39) |
missense |
probably benign |
0.00 |
R9454:Scmh1
|
UTSW |
4 |
120,372,276 (GRCm39) |
missense |
probably benign |
|
R9487:Scmh1
|
UTSW |
4 |
120,320,284 (GRCm39) |
nonsense |
probably null |
|
R9617:Scmh1
|
UTSW |
4 |
120,340,827 (GRCm39) |
missense |
probably damaging |
1.00 |
R9775:Scmh1
|
UTSW |
4 |
120,340,820 (GRCm39) |
missense |
probably benign |
|
Z1176:Scmh1
|
UTSW |
4 |
120,335,239 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Protein Function and Prediction |
Schm1 is a mammalian homologue of Drosophila Sex comb on midleg (Scm) and member of the Polycomb group of genes that maintain the appropriate expression patterns of developmental regulators (e.g., Hox genes) (1). Polycomb proteins form multimeric protein complexes [i.e., polycomb repressive complexes 1 (Prc1) and change local chromatin structure (2;3). Schm1 mediates the survival of late pachytene spermatocytes and it has been proposed that Schm1, within the Prc1, functions during spermatogensis (2).
|
Expression/Localization |
Scmh1 is expressed throughout embryogenesis (1). In adult tissues Schmh1 is most abundant in testis and least abundant in the spleen; it is readily detected in the heart, brain, lung, liver, skeletal muscle, and kidney (1).
|
Background |
Scmh1tm1Hko/tm1Hko; MGI: 3706668
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Mice homozygous for a mutation in this gene display partial penetrance of posterior vertebral transformations and male infertility with azoospermia and arrest of spermatogenesis (4). Approximately half the Scmh1-/- males were infertile, which correlates with an accelerated apoptosis of postmitotic pachytene spermatocytes (4).
|
References |
1. Tomotsune, D., Takihara, Y., Berger, J., Duhl, D., Joo, S., Kyba, M., Shirai, M., Ohta, H., Matsuda, Y., Honda, B. M., Simon, J., Shimada, K., Brock, H. W., and Randazzo, F. (1999) A Novel Member of Murine Polycomb-Group Proteins, Sex Comb on Midleg Homolog Protein, is Highly Conserved, and Interacts with RAE28/mph1 in Vitro. Differentiation. 65, 229-239.
2. Takada, Y., Isono, K., Shinga, J., Turner, J. M., Kitamura, H., Ohara, O., Watanabe, G., Singh, P. B., Kamijo, T., Jenuwein, T., Burgoyne, P. S., and Koseki, H. (2007) Mammalian Polycomb Scmh1 Mediates Exclusion of Polycomb Complexes from the XY Body in the Pachytene Spermatocytes. Development. 134, 579-590.
3. Levine, S. S., Weiss, A., Erdjument-Bromage, H., Shao, Z., Tempst, P., and Kingston, R. E. (2002) The Core of the Polycomb Repressive Complex is Compositionally and Functionally Conserved in Flies and Humans. Mol Cell Biol. 22, 6070-6078.
4. Takada, Y., Isono, K., Shinga, J., Turner, J. M., Kitamura, H., Ohara, O., Watanabe, G., Singh, P. B., Kamijo, T., Jenuwein, T., Burgoyne, P. S., and Koseki, H. (2007) Mammalian Polycomb Scmh1 Mediates Exclusion of Polycomb Complexes from the XY Body in the Pachytene Spermatocytes. Development. 134, 579-590.
|
Posted On |
2012-10-29 |
Science Writer |
Anne Murray |