Mutagenetix > Incidental Mutation

Incidental Mutation 'R1172:C9orf72'

99532

Institutional Source

Beutler Lab

Gene Symbol

C9orf72

Ensembl Gene

ENSMUSG00000028300

Gene Name

C9orf72, member of C9orf72-SMCR8 complex

Synonyms

Dennd9, 3110043O21Rik

MMRRC Submission

039245-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1172 (G1)

Quality Score

225

Status

Validated

Chromosome

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

Domain	Start	End	E-Value	Type
Pfam:C9orf72-like	60	325	6.8e-90	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108126

SMART Domains

Protein: ENSMUSP00000103761
Gene: ENSMUSG00000028300

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.6%
20x: 93.5%

Validation Efficiency

98% (62/63)

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Accsl	A	T	2: 93,696,589 (GRCm39)		probably benign	Het
Adam7	T	G	14: 68,752,370 (GRCm39)	K371N	probably damaging	Het
Adgrv1	A	T	13: 81,705,182 (GRCm39)	S1543T	probably damaging	Het
Agbl4	A	T	4: 111,513,515 (GRCm39)		probably benign	Het
Arid1b	T	A	17: 5,389,575 (GRCm39)	I1707N	probably damaging	Het
Atp10a	T	C	7: 58,453,514 (GRCm39)	V864A	probably benign	Het
Bivm	A	G	1: 44,165,942 (GRCm39)	T131A	probably benign	Het
Bst1	A	G	5: 43,982,750 (GRCm39)		probably null	Het
Cblb	T	C	16: 52,006,603 (GRCm39)		probably benign	Het
Ccdc28b	T	C	4: 129,514,682 (GRCm39)		probably benign	Het
Cmas	G	T	6: 142,702,604 (GRCm39)	G36C	probably benign	Het
Eml6	A	G	11: 29,699,824 (GRCm39)	S1771P	possibly damaging	Het
Epc1	A	C	18: 6,490,525 (GRCm39)	Y31D	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
Fermt2	T	C	14: 45,697,425 (GRCm39)	D642G	possibly damaging	Het
Fmnl2	A	T	2: 52,962,286 (GRCm39)	N257I	probably damaging	Het
Fry	G	A	5: 150,404,959 (GRCm39)	W793*	probably null	Het
Fsd2	T	C	7: 81,209,518 (GRCm39)	D108G	probably benign	Het
Glipr1l2	C	A	10: 111,919,371 (GRCm39)	L31I	possibly damaging	Het
Gm10608	CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA	CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA	9: 118,989,784 (GRCm39)		probably null	Het
Gm10801	C	T	2: 98,494,252 (GRCm39)		probably benign	Het
Gm21718	T	C	14: 51,553,348 (GRCm39)		noncoding transcript	Het
Gpld1	A	G	13: 25,141,549 (GRCm39)		probably null	Het
Gtf3c2	A	T	5: 31,325,419 (GRCm39)	Y500N	probably damaging	Het
Hbs1l	A	G	10: 21,180,537 (GRCm39)	D73G	probably damaging	Het
Idh1	G	T	1: 65,200,319 (GRCm39)	N348K	probably benign	Het
Kank4	T	C	4: 98,653,806 (GRCm39)	Y874C	probably damaging	Het
Lamc2	A	T	1: 153,042,033 (GRCm39)	S34T	probably damaging	Het
Laptm4a	T	C	12: 8,986,716 (GRCm39)	V258A	probably damaging	Het
Lrrc19	A	T	4: 94,526,626 (GRCm39)	Y310*	probably null	Het
Map3k5	G	A	10: 19,932,394 (GRCm39)		probably benign	Het
Map7	G	A	10: 20,121,045 (GRCm39)	E92K	probably damaging	Het
Mettl24	G	A	10: 40,613,704 (GRCm39)	A148T	probably benign	Het
Mosmo	A	G	7: 120,329,745 (GRCm39)	Y122C	probably benign	Het
Ncr1	T	A	7: 4,341,120 (GRCm39)	I37N	probably benign	Het
Nkx3-1	T	C	14: 69,429,434 (GRCm39)	S151P	probably damaging	Het
Npm2	T	A	14: 70,889,661 (GRCm39)	K54*	probably null	Het
Npr1	T	A	3: 90,368,689 (GRCm39)	D457V	probably benign	Het
Nudt21	T	C	8: 94,757,757 (GRCm39)		probably benign	Het
Pcnt	A	T	10: 76,228,878 (GRCm39)		probably null	Het
Pik3r4	G	T	9: 105,540,373 (GRCm39)	G754C	probably damaging	Het
Rftn2	A	G	1: 55,250,376 (GRCm39)	V123A	probably damaging	Het
Rpa1	A	T	11: 75,203,219 (GRCm39)	V392D	probably damaging	Het
Rxfp2	T	C	5: 149,975,021 (GRCm39)	V210A	probably benign	Het
Slc45a4	C	T	15: 73,477,278 (GRCm39)		probably benign	Het
Syndig1l	T	A	12: 84,725,942 (GRCm39)		probably null	Het
Tctn1	G	A	5: 122,389,752 (GRCm39)	R257*	probably null	Het
Tenm4	A	T	7: 96,497,251 (GRCm39)	E1179V	probably damaging	Het
Txlnb	A	G	10: 17,718,504 (GRCm39)	N445S	probably benign	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
Vdr	A	T	15: 97,767,214 (GRCm39)	Y185N	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
Vmn2r87	T	C	10: 130,313,453 (GRCm39)	T438A	probably benign	Het
Xrcc6	A	G	15: 81,915,364 (GRCm39)	D94G	probably damaging	Het
Ywhaq	T	C	12: 21,445,024 (GRCm39)	N207S	probably benign	Het
Zfp185	A	T	X: 72,042,929 (GRCm39)	E138D	possibly damaging	Het
Zfp981	G	A	4: 146,622,221 (GRCm39)	S382N	probably benign	Het

Other mutations in C9orf72

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R1175: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