Mutagenetix > Incidental Mutation

Incidental Mutation 'R0471:C9orf72'

46742

Institutional Source

Beutler Lab

Gene Symbol

C9orf72

Ensembl Gene

ENSMUSG00000028300

Gene Name

C9orf72, member of C9orf72-SMCR8 complex

Synonyms

Dennd9, 3110043O21Rik

MMRRC Submission

038671-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0471 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

35191285-35226153 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 35193257 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 232 (T232I)

Ref Sequence

ENSEMBL: ENSMUSP00000103761 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000084724] [ENSMUST00000108126] [ENSMUST00000108127]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000084724
AA Change: T396I

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000081775
Gene: ENSMUSG00000028300
AA Change: T396I

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

Predicted Effect

probably benign
Transcript: ENSMUST00000108126
AA Change: T232I

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000103761
Gene: ENSMUSG00000028300
AA Change: T232I

Domain	Start	End	E-Value	Type
Pfam:C9orf72-like	1	161	2e-56	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108127
AA Change: T396I

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000103762
Gene: ENSMUSG00000028300
AA Change: T396I

Domain	Start	End	E-Value	Type
Pfam:C9orf72-like	61	324	1.9e-99	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142628

Meta Mutation Damage Score

0.0719

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.1%
20x: 94.9%

Validation Efficiency

100% (67/67)

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: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acp6	T	C	3: 97,075,891 (GRCm39)		probably null	Het
Adam33	C	A	2: 130,896,399 (GRCm39)	G437C	probably damaging	Het
Aldh1a1	T	A	19: 20,579,377 (GRCm39)	M1K	probably null	Het
Amotl2	C	A	9: 102,597,718 (GRCm39)	P126Q	probably damaging	Het
Ap1g1	T	A	8: 110,580,275 (GRCm39)	M576K	possibly damaging	Het
Apob	C	A	12: 8,040,406 (GRCm39)	A581E	probably damaging	Het
Asb7	A	T	7: 66,328,907 (GRCm39)	D44E	probably damaging	Het
Bcl2	G	A	1: 106,640,292 (GRCm39)	R107C	probably damaging	Het
Ccdc65	A	T	15: 98,615,348 (GRCm39)	H118L	probably benign	Het
Cdc25b	A	G	2: 131,039,204 (GRCm39)	E523G	probably damaging	Het
Cdk11b	A	G	4: 155,731,999 (GRCm39)		probably benign	Het
Cilk1	G	T	9: 78,062,799 (GRCm39)		probably null	Het
Clec1b	A	G	6: 129,378,570 (GRCm39)		probably benign	Het
Cntrl	A	G	2: 35,017,392 (GRCm39)	T400A	probably benign	Het
Cpne4	T	G	9: 104,899,481 (GRCm39)		probably null	Het
Cyp2j6	T	A	4: 96,419,985 (GRCm39)	R249*	probably null	Het
Dock2	T	C	11: 34,579,380 (GRCm39)	I678V	probably benign	Het
Dqx1	C	T	6: 83,036,407 (GRCm39)		probably benign	Het
Dsp	A	T	13: 38,377,326 (GRCm39)	K1704*	probably null	Het
Eif2b2	T	C	12: 85,266,957 (GRCm39)	F121S	probably benign	Het
Ephx4	T	C	5: 107,561,379 (GRCm39)	V69A	possibly damaging	Het
Epn2	T	C	11: 61,426,134 (GRCm39)	Q281R	probably damaging	Het
Fgf3	A	C	7: 144,396,547 (GRCm39)	D187A	probably damaging	Het
Galnt18	C	A	7: 111,378,506 (GRCm39)		probably benign	Het
Gm4871	C	T	5: 144,968,402 (GRCm39)		probably benign	Het
Inpp4b	T	C	8: 82,768,528 (GRCm39)	I679T	possibly damaging	Het
Itpkb	A	G	1: 180,245,820 (GRCm39)	E779G	probably damaging	Het
Itsn1	G	A	16: 91,696,477 (GRCm39)	V27M	probably damaging	Het
Lrp2	C	A	2: 69,355,578 (GRCm39)	R422L	probably damaging	Het
Mmp25	G	A	17: 23,858,858 (GRCm39)	A231V	possibly damaging	Het
Mprip	T	C	11: 59,650,561 (GRCm39)	S1422P	probably damaging	Het
Mro	A	T	18: 74,009,860 (GRCm39)	Q176L	probably benign	Het
Mrpl12	A	G	11: 120,379,229 (GRCm39)	E192G	probably damaging	Het
Myo5b	A	T	18: 74,862,025 (GRCm39)		probably benign	Het
Ncam2	G	T	16: 80,997,772 (GRCm39)		probably benign	Het
Nip7	T	C	8: 107,783,949 (GRCm39)	L63P	probably damaging	Het
Nsd3	T	C	8: 26,138,450 (GRCm39)		probably benign	Het
Nup98	A	T	7: 101,788,004 (GRCm39)	V1022D	probably benign	Het
Or2y1e	T	A	11: 49,218,744 (GRCm39)	C169S	probably damaging	Het
Or5d43	A	G	2: 88,104,559 (GRCm39)	V278A	possibly damaging	Het
Or5h22	A	G	16: 58,894,633 (GRCm39)	I270T	probably benign	Het
Or7g28	A	T	9: 19,272,177 (GRCm39)	L158*	probably null	Het
P4ha2	T	C	11: 54,008,434 (GRCm39)	Y214H	possibly damaging	Het
Pacrg	A	T	17: 10,795,407 (GRCm39)	F184L	possibly damaging	Het
Parpbp	T	A	10: 87,929,569 (GRCm39)	R426S	probably damaging	Het
Pcdhb5	T	A	18: 37,454,359 (GRCm39)	Y246*	probably null	Het
Pik3cg	T	A	12: 32,244,770 (GRCm39)	T895S	probably damaging	Het
Prkch	T	C	12: 73,738,426 (GRCm39)	Y178H	probably benign	Het
Rusc2	G	T	4: 43,425,486 (GRCm39)	R1197L	probably damaging	Het
Svep1	T	C	4: 58,054,700 (GRCm39)	E3296G	possibly damaging	Het
Svs3a	A	G	2: 164,131,801 (GRCm39)	K123R	probably benign	Het
Sycp2l	A	G	13: 41,304,006 (GRCm39)		probably null	Het
Syne3	T	C	12: 104,909,685 (GRCm39)	H717R	probably benign	Het
Tiprl	A	G	1: 165,050,092 (GRCm39)		probably null	Het
Trim24	T	G	6: 37,892,130 (GRCm39)	V151G	possibly damaging	Het
Trim33	T	C	3: 103,234,217 (GRCm39)	V56A	possibly damaging	Het
Trim67	C	A	8: 125,521,397 (GRCm39)	T253K	probably benign	Het
Trip12	T	C	1: 84,703,928 (GRCm39)	E698G	probably damaging	Het
Tspan14	T	C	14: 40,637,353 (GRCm39)	D145G	probably damaging	Het
Ushbp1	G	A	8: 71,847,021 (GRCm39)	Q204*	probably null	Het
Vmn1r71	G	C	7: 10,482,019 (GRCm39)	S223C	possibly damaging	Het
Vmn2r75	G	T	7: 85,814,721 (GRCm39)	N257K	probably benign	Het
Washc4	T	C	10: 83,394,598 (GRCm39)		probably benign	Het
Zc3h7b	G	A	15: 81,666,169 (GRCm39)	D560N	probably damaging	Het
Zscan21	T	C	5: 138,123,402 (GRCm39)	V27A	probably benign	Het
Zzef1	A	C	11: 72,813,937 (GRCm39)	E2842A	probably damaging	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
R1172:C9orf72	UTSW	4	35,218,630 (GRCm39)	missense	probably damaging	0.99
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

PCR Primer
(F):5'- TGTAACAGCAGGTGTGACTGTGAAG -3'
(R):5'- TCTCTGAAGCTGAAAAGTCCCCTCC -3'

Sequencing Primer
(F):5'- CTATCTTCAGGTTCCGAAGAGAC -3'
(R):5'- CACAACCTGAAGTCATTGACTTAG -3'

Posted On

2013-06-11