Mutagenetix > Incidental Mutation

Incidental Mutation 'R8312:Grn'

641463

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

067718-MU

Accession Numbers

Essential gene?

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

Stock #

R8312 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

102321333-102327635 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 102327073 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Threonine at position 557 (K557T)

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 damaging
Transcript: ENSMUST00000049460
AA Change: K557T

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000046340
Gene: ENSMUSG00000034708
AA Change: K557T

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

possibly damaging
Transcript: ENSMUST00000125819
AA Change: K202T

PolyPhen 2 Score 0.937 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000134948
Gene: ENSMUSG00000034708
AA Change: K202T

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

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

SMART Domains

Protein: ENSMUSP00000134893
Gene: ENSMUSG00000034708
AA Change: K178T

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

Meta Mutation Damage Score

0.6329

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

100% (68/68)

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: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcd4	T	C	12: 84,662,190 (GRCm39)	R23G	probably damaging	Het
Abraxas2	A	G	7: 132,478,329 (GRCm39)	Y163C	probably damaging	Het
Acnat1	A	T	4: 49,449,142 (GRCm39)	L208*	probably null	Het
Agbl5	A	G	5: 31,051,850 (GRCm39)	E556G	probably damaging	Het
Ampd2	C	A	3: 107,987,432 (GRCm39)	V134L	probably benign	Het
Arih2	A	G	9: 108,521,473 (GRCm39)	S2P	probably damaging	Het
C87436	T	A	6: 86,434,813 (GRCm39)	L387Q	probably damaging	Het
Card9	A	T	2: 26,247,801 (GRCm39)	Y183*	probably null	Het
Cdk14	T	C	5: 4,944,141 (GRCm39)	D394G	probably benign	Het
Cep135	C	T	5: 76,784,746 (GRCm39)	S947L	probably damaging	Het
Cfb	T	C	17: 35,077,121 (GRCm39)	K505E	probably benign	Het
Cnot4	T	A	6: 35,000,076 (GRCm39)	D708V	probably damaging	Het
Col16a1	T	A	4: 129,948,244 (GRCm39)	L281M	unknown	Het
Col6a3	G	T	1: 90,741,412 (GRCm39)	D673E	possibly damaging	Het
Ctdnep1	G	A	11: 69,879,527 (GRCm39)	S150N	probably benign	Het
Fanca	T	A	8: 123,996,549 (GRCm39)		probably benign	Het
Fras1	T	A	5: 96,736,050 (GRCm39)	N548K	probably benign	Het
Gbp2b	A	G	3: 142,304,812 (GRCm39)	M83V	probably benign	Het
Gbp2b	C	A	3: 142,304,815 (GRCm39)	P84T	probably damaging	Het
Gli2	A	T	1: 118,795,842 (GRCm39)		probably benign	Het
Greb1l	A	G	18: 10,511,587 (GRCm39)		probably benign	Het
Hapln1	C	T	13: 89,749,563 (GRCm39)	A36V	probably benign	Het
Heg1	C	T	16: 33,547,045 (GRCm39)	R635W	probably benign	Het
Hivep1	C	A	13: 42,308,653 (GRCm39)	Q298K	possibly damaging	Het
Hmcn1	A	G	1: 150,614,515 (GRCm39)	I1297T	probably damaging	Het
Hp1bp3	T	A	4: 137,950,750 (GRCm39)		probably benign	Het
Htr4	C	G	18: 62,570,549 (GRCm39)	F201L	probably damaging	Het
Insrr	C	G	3: 87,707,791 (GRCm39)	Q78E	possibly damaging	Het
Itga6	A	T	2: 71,686,297 (GRCm39)	M1072L	probably benign	Het
Kdsr	A	G	1: 106,675,216 (GRCm39)		probably null	Het
Klhl7	T	C	5: 24,339,965 (GRCm39)	I149T	probably damaging	Het
Lce1l	G	C	3: 92,757,766 (GRCm39)	P31A	unknown	Het
Mag	T	C	7: 30,610,894 (GRCm39)	Y116C	probably damaging	Het
Mast2	A	G	4: 116,287,683 (GRCm39)	S131P	probably benign	Het
Mlec	C	A	5: 115,288,266 (GRCm39)		probably null	Het
Mrap2	G	A	9: 87,051,712 (GRCm39)		probably null	Het
Myo5b	A	G	18: 74,867,033 (GRCm39)	K1395E	probably damaging	Het
Nipa2	G	A	7: 55,583,050 (GRCm39)	Q232*	probably null	Het
Nsd3	C	T	8: 26,153,268 (GRCm39)	T536M	probably damaging	Het
Oit3	T	C	10: 59,274,632 (GRCm39)	N56S	probably benign	Het
Or10p22	A	G	10: 128,826,347 (GRCm39)	T189A	probably benign	Het
Or13c7	A	T	4: 43,854,461 (GRCm39)	I51F	probably benign	Het
Or2m13	T	C	16: 19,225,987 (GRCm39)	M260V	probably benign	Het
Pax3	C	T	1: 78,172,006 (GRCm39)	R68Q	probably damaging	Het
Pcnx2	G	T	8: 126,489,589 (GRCm39)	H1668Q	possibly damaging	Het
Peg10	GC	GCTCC	6: 4,756,452 (GRCm39)		probably benign	Het
Pkd1	A	G	17: 24,786,102 (GRCm39)	S463G	probably benign	Het
Plb1	C	T	5: 32,485,829 (GRCm39)	T871M	probably damaging	Het
Prdx1	A	G	4: 116,556,398 (GRCm39)	D182G	possibly damaging	Het
Prkch	T	A	12: 73,807,358 (GRCm39)	F593I	noncoding transcript	Het
Psrc1	C	T	3: 108,293,673 (GRCm39)	P194L	probably benign	Het
Ptp4a2	A	T	4: 129,733,427 (GRCm39)	I18L	probably benign	Het
Samd10	A	T	2: 181,238,668 (GRCm39)	L153H	probably damaging	Het
Shc3	T	G	13: 51,596,754 (GRCm39)	H423P	probably damaging	Het
Siae	A	T	9: 37,557,593 (GRCm39)	I467F		Het
Slc27a5	C	T	7: 12,725,214 (GRCm39)	R411Q	probably damaging	Het
Spata24	A	G	18: 35,793,861 (GRCm39)	I56T	probably benign	Het
Spns3	G	A	11: 72,390,534 (GRCm39)	T407M	probably damaging	Het
Spta1	G	A	1: 174,067,777 (GRCm39)	C2068Y	probably damaging	Het
Svs5	C	A	2: 164,080,091 (GRCm39)	G25W	probably damaging	Het
Thsd7a	T	C	6: 12,471,181 (GRCm39)	D479G		Het
Trhde	T	C	10: 114,249,192 (GRCm39)	Y858C	probably damaging	Het
Ttn	G	A	2: 76,781,992 (GRCm39)	R1057C	unknown	Het
Tulp4	G	T	17: 6,257,333 (GRCm39)		probably null	Het
Tyk2	T	C	9: 21,026,945 (GRCm39)	T613A	possibly damaging	Het
Ugt2b37	T	C	5: 87,390,799 (GRCm39)	K356R	probably benign	Het
Vmn1r39	A	G	6: 66,781,841 (GRCm39)	V159A	noncoding transcript	Het
Vps35	A	G	8: 86,001,498 (GRCm39)	V440A	possibly damaging	Het
Zmym6	A	G	4: 127,017,627 (GRCm39)	N1136S	probably damaging	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
R0395:Grn	UTSW	11	102,327,049 (GRCm39)	missense	probably benign	0.03
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
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'- ACCTGCAATGTGAAGGCGAG -3'
(R):5'- CCTTACAGTAGCGGTCTTGG -3'

Sequencing Primer
(F):5'- TGTGAAGGCGAGGACCTGTG -3'
(R):5'- ATGTCCCAGCGAGGAATCTTC -3'

Posted On

2020-07-28