Incidental Mutation 'R1175:C9orf72'
ID 99910
Institutional Source Beutler Lab
Gene Symbol C9orf72
Ensembl Gene ENSMUSG00000028300
Gene Name C9orf72, member of C9orf72-SMCR8 complex
Synonyms Dennd9, 3110043O21Rik
MMRRC Submission 039248-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1175 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 35191285-35226153 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 35218630 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Aspartic acid at position 76 (E76D)
Ref Sequence ENSEMBL: ENSMUSP00000103762 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000084724] [ENSMUST00000108126] [ENSMUST00000108127]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000084724
AA Change: E76D

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000081775
Gene: ENSMUSG00000028300
AA Change: E76D

DomainStartEndE-ValueType
Pfam:C9orf72-like 60 325 6.8e-90 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000108126
SMART Domains Protein: ENSMUSP00000103761
Gene: ENSMUSG00000028300

DomainStartEndE-ValueType
Pfam:C9orf72-like 1 161 2e-56 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000108127
AA Change: E76D

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000103762
Gene: ENSMUSG00000028300
AA Change: E76D

DomainStartEndE-ValueType
Pfam:C9orf72-like 61 324 1.9e-99 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130538
Predicted Effect noncoding transcript
Transcript: ENSMUST00000149138
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156472
Meta Mutation Damage Score 0.2416 question?
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 97.8%
  • 10x: 94.7%
  • 20x: 88.0%
Validation Efficiency 100% (74/74)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]
PHENOTYPE: Nullizygous mice show splenomegaly and lymphadenopathy. Homozygotes for one allele show reduced body weight, hematocrit and hemoglobin content, lymphopenia, neutrophilia, social interaction deficits and premature death. Homozygotes for another allele show altered macrophage and microglia physiology. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2610318N02Rik T A 16: 16,935,446 (GRCm39) H214L probably benign Het
Abca17 T C 17: 24,508,325 (GRCm39) E1070G possibly damaging Het
Accsl A T 2: 93,696,589 (GRCm39) probably benign Het
Akp3 G A 1: 87,055,593 (GRCm39) G547R unknown Het
Anapc1 C A 2: 128,522,108 (GRCm39) C150F probably damaging Het
Aoc1l3 C A 6: 48,967,173 (GRCm39) P707H probably damaging Het
Arhgef18 T A 8: 3,439,023 (GRCm39) probably benign Het
Borcs5 T A 6: 134,687,096 (GRCm39) N150K probably damaging Het
Cdh20 G A 1: 109,988,862 (GRCm39) V255I probably benign Het
Cntnap5c C A 17: 58,671,241 (GRCm39) T1143K possibly damaging Het
Col7a1 A C 9: 108,784,402 (GRCm39) T137P unknown Het
Defb8 C T 8: 19,495,910 (GRCm39) G50E probably damaging Het
Dimt1 T A 13: 107,086,193 (GRCm39) probably benign Het
Dnajb11 T A 16: 22,689,423 (GRCm39) D281E probably damaging Het
Eci2 G T 13: 35,177,087 (GRCm39) N24K probably damaging Het
Fbn1 A T 2: 125,236,607 (GRCm39) C358S probably benign Het
Fbxl13 A T 5: 21,825,602 (GRCm39) probably benign Het
Fbxw11 T C 11: 32,661,922 (GRCm39) C121R probably damaging Het
Fsd2 T C 7: 81,209,518 (GRCm39) D108G probably benign Het
Gab1 C A 8: 81,511,471 (GRCm39) R458L probably damaging Het
Ghrhr T A 6: 55,365,254 (GRCm39) L416* probably null Het
Glipr1l2 C A 10: 111,919,371 (GRCm39) L31I possibly damaging Het
Gm1818 A G 12: 48,602,982 (GRCm39) noncoding transcript Het
Gm19965 T A 1: 116,748,550 (GRCm39) probably benign Het
Gpr149 A G 3: 62,511,888 (GRCm39) L37P probably damaging Het
Hoxa9 A G 6: 52,202,693 (GRCm39) I131T probably damaging Het
Itpkc T C 7: 26,927,195 (GRCm39) I240V probably benign Het
Jakmip3 A G 7: 138,629,515 (GRCm39) D552G probably damaging Het
Kank4 T C 4: 98,653,806 (GRCm39) Y874C probably damaging Het
Kdm3a T C 6: 71,577,011 (GRCm39) E768G possibly damaging Het
Klf6 A G 13: 5,911,711 (GRCm39) D25G probably benign Het
Lamc1 T C 1: 153,122,977 (GRCm39) probably benign Het
Laptm4a T C 12: 8,986,716 (GRCm39) V258A probably damaging Het
Map3k19 A G 1: 127,751,617 (GRCm39) V578A probably benign Het
Mast1 T C 8: 85,651,956 (GRCm39) E342G probably benign Het
Mgat5b T C 11: 116,868,622 (GRCm39) L515P probably damaging Het
Mink1 A G 11: 70,502,166 (GRCm39) D985G probably benign Het
Mphosph9 A G 5: 124,453,739 (GRCm39) V191A possibly damaging Het
Muc6 C T 7: 141,234,368 (GRCm39) G708S probably damaging Het
Pcnt A T 10: 76,228,878 (GRCm39) probably null Het
Psmd8 A T 7: 28,875,598 (GRCm39) Y174N probably damaging Het
Ptgdr2 C A 19: 10,918,292 (GRCm39) R270S possibly damaging Het
Rasal2 A G 1: 156,975,218 (GRCm39) M1172T probably damaging Het
Rif1 A G 2: 51,997,640 (GRCm39) probably benign Het
Rnf123 C T 9: 107,954,572 (GRCm39) R48H probably benign Het
Rsrc1 T C 3: 67,263,551 (GRCm39) probably benign Het
Rxfp2 T C 5: 149,975,021 (GRCm39) V210A probably benign Het
Serpinb9d C T 13: 33,384,608 (GRCm39) P195L probably benign Het
Sis A G 3: 72,865,437 (GRCm39) probably benign Het
Skint4 T C 4: 111,981,793 (GRCm39) M246T probably benign Het
Snrnp200 C A 2: 127,070,997 (GRCm39) R1093S probably damaging Het
Sp100 A G 1: 85,629,141 (GRCm39) N471D possibly damaging Het
Spmip4 T A 6: 50,566,121 (GRCm39) K118M probably damaging Het
Ssxb8 T G X: 8,556,062 (GRCm39) H88P probably damaging Het
Sufu T C 19: 46,389,703 (GRCm39) probably null Het
Synpo2l G A 14: 20,718,235 (GRCm39) T10I possibly damaging Het
Tdo2 A T 3: 81,881,683 (GRCm39) S40R probably damaging Het
Tent4b T A 8: 88,978,635 (GRCm39) F445L probably damaging Het
Terb1 G A 8: 105,210,938 (GRCm39) T363I probably benign Het
Timd4 C T 11: 46,708,498 (GRCm39) P175S probably damaging Het
Tlr3 C A 8: 45,850,171 (GRCm39) V833L probably damaging Het
Tpst2 T A 5: 112,455,911 (GRCm39) M150K probably damaging Het
Trim67 T A 8: 125,543,774 (GRCm39) V378E probably damaging Het
Tyrp1 C T 4: 80,763,105 (GRCm39) Q331* probably null Het
Ubap2l A T 3: 89,930,807 (GRCm39) S413T probably benign Het
Uimc1 G A 13: 55,176,415 (GRCm39) T701I possibly damaging Het
Vangl2 G T 1: 171,832,353 (GRCm39) T501N probably damaging Het
Vmn1r60 A G 7: 5,547,621 (GRCm39) S160P probably benign Het
Vmn2r66 G T 7: 84,654,799 (GRCm39) D503E probably benign Het
Vmn2r72 T A 7: 85,401,152 (GRCm39) E89V probably damaging Het
Zfp457 G A 13: 67,441,748 (GRCm39) P180S probably damaging Het
Other mutations in C9orf72
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00473:C9orf72 APN 4 35,213,616 (GRCm39) missense possibly damaging 0.57
IGL00718:C9orf72 APN 4 35,213,015 (GRCm39) missense probably damaging 1.00
IGL01284:C9orf72 APN 4 35,218,808 (GRCm39) missense probably damaging 0.96
IGL01998:C9orf72 APN 4 35,194,179 (GRCm39) missense probably benign 0.30
IGL02185:C9orf72 APN 4 35,197,046 (GRCm39) missense probably damaging 1.00
IGL02403:C9orf72 APN 4 35,205,887 (GRCm39) splice site probably benign
IGL02823:C9orf72 APN 4 35,213,031 (GRCm39) missense probably damaging 0.98
R0194:C9orf72 UTSW 4 35,197,207 (GRCm39) missense probably damaging 1.00
R0471:C9orf72 UTSW 4 35,193,257 (GRCm39) missense probably benign 0.01
R1172:C9orf72 UTSW 4 35,218,630 (GRCm39) missense probably damaging 0.99
R1765:C9orf72 UTSW 4 35,197,098 (GRCm39) missense probably damaging 1.00
R4326:C9orf72 UTSW 4 35,225,985 (GRCm39) unclassified probably benign
R4327:C9orf72 UTSW 4 35,225,985 (GRCm39) unclassified probably benign
R4328:C9orf72 UTSW 4 35,225,985 (GRCm39) unclassified probably benign
R4679:C9orf72 UTSW 4 35,226,033 (GRCm39) unclassified probably benign
R4844:C9orf72 UTSW 4 35,213,565 (GRCm39) missense possibly damaging 0.47
R5150:C9orf72 UTSW 4 35,193,270 (GRCm39) missense possibly damaging 0.92
R5528:C9orf72 UTSW 4 35,213,556 (GRCm39) missense probably benign 0.18
R5789:C9orf72 UTSW 4 35,226,112 (GRCm39) unclassified probably benign
R7790:C9orf72 UTSW 4 35,192,997 (GRCm39) missense unknown
R7805:C9orf72 UTSW 4 35,194,170 (GRCm39) missense
R8115:C9orf72 UTSW 4 35,218,763 (GRCm39) missense
R9049:C9orf72 UTSW 4 35,192,964 (GRCm39) missense unknown
R9327:C9orf72 UTSW 4 35,205,883 (GRCm39) missense
R9373:C9orf72 UTSW 4 35,196,985 (GRCm39) missense
R9590:C9orf72 UTSW 4 35,218,557 (GRCm39) missense
R9591:C9orf72 UTSW 4 35,218,557 (GRCm39) missense
Predicted Primers
Posted On 2014-01-15