Mutagenetix > Incidental Mutation

Incidental Mutation 'R0395:Grn'

31973

Institutional Source

Beutler Lab

Gene Symbol

Grn

Ensembl Gene

ENSMUSG00000034708

Gene Name

granulin

Synonyms

epithelin, progranulin, Pgrn, PC cell-derived growth factor, acrogranulin

MMRRC Submission

038601-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.448) question?

Stock #

R0395 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

102321333-102327635 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 102327049 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 549 (V549A)

Ref Sequence

ENSEMBL: ENSMUSP00000046340 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049057] [ENSMUST00000049460] [ENSMUST00000125819] [ENSMUST00000129997]

AlphaFold

P28798

Predicted Effect

probably benign
Transcript: ENSMUST00000049057

SMART Domains

Protein: ENSMUSP00000038486
Gene: ENSMUSG00000034685

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
Pfam:UPF0560	41	820	N/A	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000049460
AA Change: V549A

PolyPhen 2 Score 0.032 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000046340
Gene: ENSMUSG00000034708
AA Change: V549A

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
GRAN	74	125	1.32e-22	SMART
GRAN	138	190	7.38e-26	SMART
GRAN	220	272	5.76e-28	SMART
GRAN	295	346	1.19e-29	SMART
GRAN	377	427	1.84e-26	SMART
GRAN	455	506	7.1e-28	SMART
GRAN	530	581	1.48e-25	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123500

Predicted Effect

probably benign
Transcript: ENSMUST00000125819
AA Change: V194A

PolyPhen 2 Score 0.019 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000134948
Gene: ENSMUSG00000034708
AA Change: V194A

Domain	Start	End	E-Value	Type
GRAN	42	72	5.03e-4	SMART
GRAN	100	151	7.1e-28	SMART
GRAN	175	226	1.48e-25	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127530

Predicted Effect

probably benign
Transcript: ENSMUST00000129997

SMART Domains

Protein: ENSMUSP00000135739
Gene: ENSMUSG00000034708

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
GRAN	61	112	1.32e-22	SMART
GRAN	125	177	7.38e-26	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135517

Predicted Effect

unknown
Transcript: ENSMUST00000177428
AA Change: V170A

SMART Domains

Protein: ENSMUSP00000134893
Gene: ENSMUSG00000034708
AA Change: V170A

Domain	Start	End	E-Value	Type
GRAN	1	49	8.68e-23	SMART
GRAN	77	128	7.1e-28	SMART
GRAN	152	180	3.98e-2	SMART
low complexity region	244	259	N/A	INTRINSIC
low complexity region	309	324	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145190

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000138451

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000176953

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148580

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000152015

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.1%
3x: 98.1%
10x: 95.9%
20x: 91.4%

Validation Efficiency

98% (103/105)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for some knock-out alleles display enhanced macrophage functions. Mice homozygous for another knock-out allele display reproductive and behavioral abnormalities. Mice homozygous for a third null allele display premature death and increased cellular aging. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 103 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921517D22Rik	T	C	13: 59,837,470 (GRCm39)	K205R	possibly damaging	Het
9630041A04Rik	A	T	9: 101,819,934 (GRCm39)	N118I	probably damaging	Het
AAdacl4fm3	A	G	4: 144,429,765 (GRCm39)	V408A	probably benign	Het
Acsm2	G	A	7: 119,174,969 (GRCm39)	D245N	probably damaging	Het
Adgrv1	A	T	13: 81,534,072 (GRCm39)	H5836Q	probably benign	Het
Ahcyl2	T	C	6: 29,886,167 (GRCm39)	V391A	probably damaging	Het
Alcam	A	T	16: 52,130,227 (GRCm39)	M41K	probably benign	Het
Aldh3b3	A	C	19: 4,016,472 (GRCm39)	E363D	probably benign	Het
Alk	A	G	17: 72,910,526 (GRCm39)	V60A	probably damaging	Het
Als2cl	G	A	9: 110,727,152 (GRCm39)	R906H	probably damaging	Het
Ap5z1	T	C	5: 142,456,317 (GRCm39)		probably benign	Het
Apba2	T	A	7: 64,393,156 (GRCm39)	I547N	probably benign	Het
Apol10b	A	T	15: 77,469,840 (GRCm39)	D112E	probably damaging	Het
Ash1l	C	A	3: 88,965,896 (GRCm39)	R2433S	probably damaging	Het
Cachd1	T	C	4: 100,810,402 (GRCm39)	F335L	probably damaging	Het
Cbfa2t3	G	T	8: 123,365,690 (GRCm39)	Q181K	probably benign	Het
Cct6b	A	G	11: 82,630,506 (GRCm39)	M265T	probably benign	Het
Cd151	G	A	7: 141,050,304 (GRCm39)	V180I	probably damaging	Het
Ces1h	T	A	8: 94,083,706 (GRCm39)	N412I	unknown	Het
Chmp7	T	C	14: 69,969,905 (GRCm39)	T12A	probably benign	Het
Clasp1	A	G	1: 118,467,061 (GRCm39)	T534A	possibly damaging	Het
Cldn15	T	A	5: 136,997,052 (GRCm39)	V31E	possibly damaging	Het
Col16a1	G	A	4: 129,966,902 (GRCm39)	G583D	probably damaging	Het
Csmd1	T	C	8: 16,396,652 (GRCm39)	N426S	probably damaging	Het
Dapp1	C	T	3: 137,641,398 (GRCm39)	C199Y	possibly damaging	Het
Dchs1	A	G	7: 105,407,745 (GRCm39)	L2029P	probably damaging	Het
Dmc1	A	G	15: 79,472,973 (GRCm39)	F158S	probably damaging	Het
Dst	C	T	1: 34,228,200 (GRCm39)	P1606L	probably damaging	Het
Dthd1	T	A	5: 62,971,676 (GRCm39)	N166K	possibly damaging	Het
Enam	A	T	5: 88,649,367 (GRCm39)	Y292F	probably damaging	Het
Esrrg	A	T	1: 187,930,832 (GRCm39)	I285F	probably damaging	Het
Fam50b	A	G	13: 34,931,220 (GRCm39)	D232G	probably damaging	Het
Fam91a1	T	A	15: 58,326,641 (GRCm39)	S792T	probably benign	Het
Fbxw22	A	C	9: 109,210,753 (GRCm39)	C419W	probably damaging	Het
Flt4	G	A	11: 49,521,170 (GRCm39)	S393N	probably benign	Het
Fras1	A	T	5: 96,917,512 (GRCm39)	T3511S	possibly damaging	Het
Frat2	A	C	19: 41,836,263 (GRCm39)	S30A	probably damaging	Het
Glp1r	T	A	17: 31,155,312 (GRCm39)	M433K	probably benign	Het
Gm10300	G	A	4: 131,802,299 (GRCm39)		probably benign	Het
Gpatch4	A	G	3: 87,961,661 (GRCm39)		probably benign	Het
Gpr22	A	T	12: 31,759,461 (GRCm39)	S220R	possibly damaging	Het
Gtf3c5	T	C	2: 28,467,930 (GRCm39)	D177G	probably damaging	Het
Htr1b	A	T	9: 81,513,704 (GRCm39)	M301K	probably benign	Het
Ifi207	A	T	1: 173,557,431 (GRCm39)	S436T	possibly damaging	Het
Ifnb1	A	T	4: 88,440,766 (GRCm39)	N82K	possibly damaging	Het
Ina	T	G	19: 47,010,358 (GRCm39)	N384K	probably damaging	Het
Kirrel2	T	C	7: 30,149,883 (GRCm39)	N541D	possibly damaging	Het
Lrp2	A	T	2: 69,263,421 (GRCm39)	I4377N	possibly damaging	Het
Lrrc37a	A	G	11: 103,355,221 (GRCm39)	V2532A	unknown	Het
Mast4	T	C	13: 102,871,781 (GRCm39)	E2529G	probably damaging	Het
Myh6	T	C	14: 55,183,777 (GRCm39)	H1719R	possibly damaging	Het
Myo5a	A	T	9: 75,101,259 (GRCm39)	H150L	probably benign	Het
Naglu	C	T	11: 100,964,933 (GRCm39)		probably benign	Het
Nags	G	A	11: 102,036,530 (GRCm39)	A40T	unknown	Het
Nav1	G	T	1: 135,460,359 (GRCm39)	Y321*	probably null	Het
Nav1	A	T	1: 135,460,361 (GRCm39)	Y321N	probably damaging	Het
Neu3	C	T	7: 99,462,985 (GRCm39)	S246N	probably benign	Het
Npy5r	C	T	8: 67,134,625 (GRCm39)	G56D	probably benign	Het
Nrxn1	A	G	17: 91,395,742 (GRCm39)	V138A	possibly damaging	Het
Nuggc	C	T	14: 65,850,921 (GRCm39)	Q264*	probably null	Het
Ogfod1	G	A	8: 94,790,156 (GRCm39)		probably null	Het
Or1o11	T	A	17: 37,756,757 (GRCm39)	F115Y	probably damaging	Het
Or2t45	A	T	11: 58,669,195 (GRCm39)	M81L	probably benign	Het
Or5b101	A	G	19: 13,005,663 (GRCm39)	F10S	probably damaging	Het
Or5p66	A	G	7: 107,885,478 (GRCm39)	V285A	probably benign	Het
Per1	T	A	11: 68,993,103 (GRCm39)	I340N	probably damaging	Het
Pkhd1	C	T	1: 20,451,771 (GRCm39)	A2175T	probably benign	Het
Pogk	A	G	1: 166,231,171 (GRCm39)	V52A	probably damaging	Het
Pou2af3	C	T	9: 51,191,834 (GRCm39)		probably benign	Het
Ppib	A	T	9: 65,973,601 (GRCm39)	T185S	possibly damaging	Het
Ptar1	G	T	19: 23,697,563 (GRCm39)	M358I	probably damaging	Het
Qser1	A	C	2: 104,593,226 (GRCm39)	I1597S	probably damaging	Het
Ranbp17	T	C	11: 33,424,896 (GRCm39)	I487V	probably benign	Het
Repin1	C	A	6: 48,574,459 (GRCm39)	R460S	probably damaging	Het
Sfmbt1	T	C	14: 30,509,574 (GRCm39)		probably benign	Het
Sh3rf1	C	T	8: 61,846,696 (GRCm39)		probably benign	Het
Shroom3	C	T	5: 92,928,762 (GRCm39)	R106C	probably damaging	Het
Siglecf	T	A	7: 43,005,399 (GRCm39)	V453D	probably damaging	Het
Slc2a9	A	G	5: 38,610,512 (GRCm39)	S96P	probably damaging	Het
Slc5a2	A	G	7: 127,866,654 (GRCm39)	Y124C	probably damaging	Het
Slf1	A	G	13: 77,254,088 (GRCm39)		probably benign	Het
Smad1	T	G	8: 80,076,411 (GRCm39)	K269T	probably benign	Het
Srp54b	G	A	12: 55,296,884 (GRCm39)	R194H	probably damaging	Het
St8sia6	T	A	2: 13,670,247 (GRCm39)	S238C	probably damaging	Het
Stat3	A	T	11: 100,780,763 (GRCm39)		probably benign	Het
Tafa2	A	T	10: 123,429,497 (GRCm39)	H37L	probably benign	Het
Tas1r2	T	A	4: 139,382,665 (GRCm39)	M101K	possibly damaging	Het
Tesc	A	G	5: 118,191,647 (GRCm39)		probably null	Het
Tle3	T	A	9: 61,317,353 (GRCm39)	M334K	probably damaging	Het
Tmem151a	A	T	19: 5,132,261 (GRCm39)	V315E	probably damaging	Het
Tmprss2	T	C	16: 97,368,245 (GRCm39)	D480G	probably damaging	Het
Trmt1	C	A	8: 85,423,741 (GRCm39)		probably null	Het
Tsr3	T	C	17: 25,461,198 (GRCm39)		probably null	Het
Ube2u	A	G	4: 100,338,845 (GRCm39)	K37E	probably benign	Het
Usp16	T	A	16: 87,272,334 (GRCm39)	D382E	probably damaging	Het
Usp9y	A	T	Y: 1,340,053 (GRCm39)	F1442Y	probably damaging	Het
Utp20	A	T	10: 88,654,457 (GRCm39)	M210K	probably damaging	Het
Utp25	T	C	1: 192,805,984 (GRCm39)	E187G	possibly damaging	Het
V1ra8	C	T	6: 90,179,991 (GRCm39)	L65F	possibly damaging	Het
Vmn2r10	T	C	5: 109,149,859 (GRCm39)	N395S	probably damaging	Het
Vmn2r100	C	A	17: 19,742,382 (GRCm39)	P252Q	possibly damaging	Het
Zfp217	C	T	2: 169,957,382 (GRCm39)	A539T	probably benign	Het
Zfp330	G	A	8: 83,491,511 (GRCm39)	Q221*	probably null	Het

Other mutations in Grn

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02422:Grn	APN	11	102,327,084 (GRCm39)	splice site	probably benign
IGL02456:Grn	APN	11	102,326,930 (GRCm39)	missense	probably benign	0.01
PIT4434001:Grn	UTSW	11	102,326,766 (GRCm39)	missense	possibly damaging	0.88
R0784:Grn	UTSW	11	102,325,328 (GRCm39)	missense	possibly damaging	0.74
R1037:Grn	UTSW	11	102,323,896 (GRCm39)	missense	possibly damaging	0.94
R1753:Grn	UTSW	11	102,324,093 (GRCm39)	missense	probably damaging	1.00
R1905:Grn	UTSW	11	102,327,276 (GRCm39)	missense	probably damaging	1.00
R3110:Grn	UTSW	11	102,324,069 (GRCm39)	missense	probably benign	0.07
R3111:Grn	UTSW	11	102,324,069 (GRCm39)	missense	probably benign	0.07
R3112:Grn	UTSW	11	102,324,069 (GRCm39)	missense	probably benign	0.07
R3974:Grn	UTSW	11	102,327,165 (GRCm39)	missense	probably damaging	1.00
R4908:Grn	UTSW	11	102,327,344 (GRCm39)	unclassified	probably benign
R4989:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5012:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5013:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5108:Grn	UTSW	11	102,325,228 (GRCm39)	missense	probably benign	0.10
R5133:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5134:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5162:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5182:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5183:Grn	UTSW	11	102,321,380 (GRCm39)	unclassified	probably benign
R5308:Grn	UTSW	11	102,327,018 (GRCm39)	missense	possibly damaging	0.96
R5350:Grn	UTSW	11	102,327,070 (GRCm39)	missense	possibly damaging	0.50
R5786:Grn	UTSW	11	102,324,869 (GRCm39)	nonsense	probably null
R6383:Grn	UTSW	11	102,327,621 (GRCm39)	unclassified	probably benign
R7679:Grn	UTSW	11	102,323,895 (GRCm39)	missense	probably benign	0.01
R7741:Grn	UTSW	11	102,326,560 (GRCm39)	missense	probably damaging	1.00
R8312:Grn	UTSW	11	102,327,073 (GRCm39)	missense	probably damaging	0.98
R8677:Grn	UTSW	11	102,324,393 (GRCm39)	missense	possibly damaging	0.94
R8682:Grn	UTSW	11	102,325,646 (GRCm39)	missense	probably benign	0.04
R8864:Grn	UTSW	11	102,327,211 (GRCm39)	missense	unknown
R9001:Grn	UTSW	11	102,327,497 (GRCm39)	missense

Predicted Primers

PCR Primer
(F):5'- ACACCTGCAATGTGAAGGCGAG -3'
(R):5'- TAGCCCTTCCTTACAGTAGCGGTC -3'

Sequencing Primer
(F):5'- TGTGAAGGCGAGGACCTG -3'
(R):5'- CGAGGAATCTTCTTTCGCAAAC -3'

Posted On

2013-04-24