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) question?
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 question?
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
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
AlleleSourceChrCoordTypePredicted EffectPPH 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
Posted On 2012-10-29
Science Writer Anne Murray