Mutagenetix > Incidental Mutation

Incidental Mutation 'R4844:C9orf72'

372037

Institutional Source

Beutler Lab

Gene Symbol

C9orf72

Ensembl Gene

ENSMUSG00000028300

Gene Name

C9orf72, member of C9orf72-SMCR8 complex

Synonyms

Dennd9, 3110043O21Rik

MMRRC Submission

042457-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4844 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

35191285-35226153 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 35213565 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 31 (V31A)

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: V195A

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000081775
Gene: ENSMUSG00000028300
AA Change: V195A

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000108126
AA Change: V31A

PolyPhen 2 Score 0.468 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000103761
Gene: ENSMUSG00000028300
AA Change: V31A

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

Predicted Effect

probably benign
Transcript: ENSMUST00000108127
AA Change: V195A

PolyPhen 2 Score 0.037 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000103762
Gene: ENSMUSG00000028300
AA Change: V195A

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: ENSMUST00000156472

Meta Mutation Damage Score

0.1212

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.6%

Validation Efficiency

97% (68/70)

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc9	T	C	6: 142,634,824 (GRCm39)	T147A	probably benign	Het
Acvrl1	T	C	15: 101,033,409 (GRCm39)	S99P	probably damaging	Het
Adamts3	T	A	5: 89,825,675 (GRCm39)	S1055C	probably damaging	Het
Aftph	T	C	11: 20,658,667 (GRCm39)		probably benign	Het
Aldh1a1	A	G	19: 20,611,764 (GRCm39)	K363E	probably benign	Het
Astn2	A	G	4: 65,562,967 (GRCm39)	V886A	possibly damaging	Het
Atad5	G	A	11: 80,005,137 (GRCm39)		probably null	Het
Ccnf	G	T	17: 24,449,331 (GRCm39)	Y482*	probably null	Het
Cfap97	A	G	8: 46,622,712 (GRCm39)	D34G	possibly damaging	Het
Chst11	G	T	10: 83,026,923 (GRCm39)	E117*	probably null	Het
Cobl	A	T	11: 12,204,740 (GRCm39)	L572Q	probably benign	Het
Coch	G	A	12: 51,649,477 (GRCm39)	G263S	probably damaging	Het
Coq4	T	C	2: 29,686,026 (GRCm39)	I205T	possibly damaging	Het
Cyp3a13	A	T	5: 137,915,813 (GRCm39)	I62K	probably benign	Het
Cyp7a1	A	G	4: 6,273,655 (GRCm39)	S84P	probably damaging	Het
Dennd10	GTCT	GT	19: 60,823,435 (GRCm39)		probably null	Het
G6pc3	G	A	11: 102,084,057 (GRCm39)		probably null	Het
Gm10576	T	C	4: 100,911,707 (GRCm39)		noncoding transcript	Het
Gm17511	G	A	7: 126,885,454 (GRCm39)		noncoding transcript	Het
Gnat2	T	C	3: 108,002,831 (GRCm39)	S80P	probably damaging	Het
Gpaa1	C	T	15: 76,216,508 (GRCm39)		probably benign	Het
Gpr107	T	A	2: 31,078,686 (GRCm39)		probably null	Het
Hormad1	T	C	3: 95,478,242 (GRCm39)	Y103H	probably damaging	Het
Ighv14-1	T	G	12: 113,895,622 (GRCm39)	Q101P	probably damaging	Het
Igsf9	A	G	1: 172,324,737 (GRCm39)	D885G	probably benign	Het
Il15ra	G	A	2: 11,723,082 (GRCm39)		probably benign	Het
Islr2	C	T	9: 58,115,517 (GRCm39)		probably benign	Het
Jak3	A	T	8: 72,134,299 (GRCm39)	N467I	possibly damaging	Het
Jarid2	T	C	13: 45,067,248 (GRCm39)	V1023A	probably damaging	Het
Kcnn2	A	T	18: 45,816,187 (GRCm39)	T333S	possibly damaging	Het
Klk14	G	A	7: 43,341,501 (GRCm39)	C51Y	probably damaging	Het
Kmt2c	T	C	5: 25,520,111 (GRCm39)	T2000A	probably benign	Het
Lpxn	A	G	19: 12,810,536 (GRCm39)	T327A	probably damaging	Het
Mxra8	A	G	4: 155,927,151 (GRCm39)	T362A	probably benign	Het
Myh6	A	G	14: 55,184,651 (GRCm39)	I1560T	possibly damaging	Het
Ndufv1	A	G	19: 4,062,574 (GRCm39)	S17P	probably benign	Het
Nwd1	A	T	8: 73,393,742 (GRCm39)	H335L	probably damaging	Het
Or1a1	A	G	11: 74,086,902 (GRCm39)	D191G	probably damaging	Het
Or2f1b	T	A	6: 42,739,394 (GRCm39)	M136K	probably damaging	Het
Otop2	G	A	11: 115,214,201 (GRCm39)		probably null	Het
Pwwp2b	C	A	7: 138,835,502 (GRCm39)	S314R	probably benign	Het
Rfx7	C	T	9: 72,500,524 (GRCm39)	Q95*	probably null	Het
Serpine2	A	T	1: 79,777,241 (GRCm39)	L192*	probably null	Het
Smpdl3b	T	C	4: 132,465,369 (GRCm39)	I322M	probably damaging	Het
Spata31d1b	C	T	13: 59,866,169 (GRCm39)	R1106C	possibly damaging	Het
Sprr2k	T	G	3: 92,336,732 (GRCm39)		probably null	Het
St8sia1	T	A	6: 142,774,996 (GRCm39)	R194S	possibly damaging	Het
Sv2a	T	A	3: 96,095,695 (GRCm39)	V337D	probably damaging	Het
Tars1	G	A	15: 11,385,281 (GRCm39)	R637W	possibly damaging	Het
Tcp11l2	G	T	10: 84,449,555 (GRCm39)	V507L	probably benign	Het
Tpr	T	C	1: 150,321,630 (GRCm39)	Y2262H	possibly damaging	Het
Vars1	A	G	17: 35,230,588 (GRCm39)	E529G	probably damaging	Het
Vash2	C	T	1: 190,710,691 (GRCm39)		probably benign	Het
Vmn1r194	T	C	13: 22,429,223 (GRCm39)	V280A	probably benign	Het
Vti1a	A	G	19: 55,380,297 (GRCm39)	T142A	probably damaging	Het
Zfp111	C	T	7: 23,898,801 (GRCm39)	C270Y	probably damaging	Het
Zfp518a	T	A	19: 40,903,340 (GRCm39)	Y1090N	probably damaging	Het
Zfp616	A	T	11: 73,975,225 (GRCm39)	Y498F	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
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
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'- CTCACGGAAAATGTGTGACTG -3'
(R):5'- AGGGTGTTTTACTCTCTGCC -3'

Sequencing Primer
(F):5'- CGGAAAATGTGTGACTGGAATATTC -3'
(R):5'- ACTCTCTGCCTCCATTTGAAATG -3'

Posted On

2016-03-01