Incidental Mutation 'R0360:Sparcl1'
ID 30037
Institutional Source Beutler Lab
Gene Symbol Sparcl1
Ensembl Gene ENSMUSG00000029309
Gene Name SPARC-like 1
Synonyms hevin, Ecm2, mast9, Sc1
MMRRC Submission 038566-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0360 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 104226977-104261599 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 104237503 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Valine at position 444 (D444V)
Ref Sequence ENSEMBL: ENSMUSP00000031249 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000031249] [ENSMUST00000199947]
AlphaFold P70663
Predicted Effect probably damaging
Transcript: ENSMUST00000031249
AA Change: D444V

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000031249
Gene: ENSMUSG00000029309
AA Change: D444V

DomainStartEndE-ValueType
signal peptide 1 16 N/A INTRINSIC
low complexity region 70 81 N/A INTRINSIC
low complexity region 90 101 N/A INTRINSIC
low complexity region 192 210 N/A INTRINSIC
low complexity region 330 340 N/A INTRINSIC
low complexity region 372 381 N/A INTRINSIC
FOLN 418 441 2.33e-5 SMART
KAZAL 441 495 3.62e-11 SMART
Pfam:SPARC_Ca_bdg 498 636 2.8e-44 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000199947
SMART Domains Protein: ENSMUSP00000143177
Gene: ENSMUSG00000029309

DomainStartEndE-ValueType
signal peptide 1 16 N/A INTRINSIC
low complexity region 70 81 N/A INTRINSIC
low complexity region 90 101 N/A INTRINSIC
low complexity region 192 210 N/A INTRINSIC
Meta Mutation Damage Score 0.2506 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.3%
  • 10x: 96.2%
  • 20x: 92.6%
Validation Efficiency 98% (93/95)
MGI Phenotype PHENOTYPE: Mice homozygous for a targeted null mutation exhibit no discernable phenotype; mice are viable and fertile with normal histology and survival. [provided by MGI curators]
Allele List at MGI

All alleles(5) : Targeted(1) Gene trapped(4)

Other mutations in this stock
Total: 95 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acp7 G A 7: 28,310,553 (GRCm39) probably benign Het
Adcyap1r1 G T 6: 55,452,508 (GRCm39) probably benign Het
Ankrd6 T C 4: 32,836,424 (GRCm39) T44A probably damaging Het
Ano7 A G 1: 93,316,380 (GRCm39) D221G probably benign Het
Bhlhe40 C A 6: 108,641,711 (GRCm39) N218K probably damaging Het
Bms1 A G 6: 118,382,251 (GRCm39) V429A probably benign Het
C7 T A 15: 5,018,444 (GRCm39) T800S probably benign Het
Camta2 G A 11: 70,574,136 (GRCm39) T127I probably damaging Het
Ccdc13 T A 9: 121,627,282 (GRCm39) N665I probably damaging Het
Ccdc157 T C 11: 4,096,663 (GRCm39) E362G probably damaging Het
Ccdc73 T A 2: 104,811,352 (GRCm39) N310K probably damaging Het
Cfap91 T A 16: 38,118,659 (GRCm39) probably null Het
Cmklr1 A T 5: 113,752,578 (GRCm39) L141H probably damaging Het
Cnst C A 1: 179,407,100 (GRCm39) A49E probably benign Het
Col5a3 C T 9: 20,683,762 (GRCm39) R1498Q unknown Het
Crybb3 T A 5: 113,223,819 (GRCm39) I197F probably damaging Het
Cryzl1 G A 16: 91,504,155 (GRCm39) P97S probably benign Het
Cubn T C 2: 13,315,318 (GRCm39) probably benign Het
Cyp2d37-ps T C 15: 82,574,253 (GRCm39) noncoding transcript Het
Cyp4a12b C A 4: 115,290,117 (GRCm39) N223K probably benign Het
D16Ertd472e A T 16: 78,344,773 (GRCm39) C112S probably benign Het
Dennd2a T C 6: 39,485,233 (GRCm39) T349A probably benign Het
Dock5 G A 14: 68,060,129 (GRCm39) probably benign Het
Dpp6 T C 5: 27,857,267 (GRCm39) L404P probably damaging Het
Dsc3 T A 18: 20,104,639 (GRCm39) T563S possibly damaging Het
Dync2h1 T A 9: 7,113,182 (GRCm39) E214D possibly damaging Het
Elac2 A G 11: 64,870,136 (GRCm39) Y67C probably damaging Het
Elmo1 A T 13: 20,748,663 (GRCm39) K503* probably null Het
Eng T C 2: 32,569,149 (GRCm39) S559P probably benign Het
Epc2 T A 2: 49,427,145 (GRCm39) V563E possibly damaging Het
Fancm A G 12: 65,122,724 (GRCm39) Y82C probably damaging Het
Flt4 A T 11: 49,527,818 (GRCm39) M924L probably benign Het
Gabpa T A 16: 84,654,275 (GRCm39) N317K possibly damaging Het
Gchfr T G 2: 118,998,327 (GRCm39) Y3* probably null Het
Gli3 G T 13: 15,899,349 (GRCm39) G912V probably benign Het
Gm10295 C A 7: 71,000,361 (GRCm39) C73F unknown Het
Gm10382 G T 5: 125,466,728 (GRCm39) probably benign Het
Gp1ba T C 11: 70,531,284 (GRCm39) probably benign Het
Gpr146 G A 5: 139,364,933 (GRCm39) probably benign Het
Hexd T A 11: 121,102,969 (GRCm39) H62Q probably benign Het
Hgd T A 16: 37,431,546 (GRCm39) probably benign Het
Hs6st1 G A 1: 36,108,266 (GRCm39) probably null Het
Icam4 A G 9: 20,941,117 (GRCm39) Y123C probably damaging Het
Il24 A G 1: 130,811,674 (GRCm39) V134A probably damaging Het
Iqcb1 G T 16: 36,692,670 (GRCm39) A562S probably damaging Het
Iqgap2 A C 13: 95,867,783 (GRCm39) probably benign Het
Islr2 T C 9: 58,107,027 (GRCm39) T78A possibly damaging Het
Kif1b A G 4: 149,347,186 (GRCm39) I330T probably damaging Het
Kirrel1 T C 3: 86,997,106 (GRCm39) Y287C probably damaging Het
Klf10 C T 15: 38,297,090 (GRCm39) V317M probably benign Het
Klhl9 T G 4: 88,638,527 (GRCm39) K571N probably benign Het
Lin37 T C 7: 30,256,438 (GRCm39) I97V possibly damaging Het
Lrrc37a C T 11: 103,391,466 (GRCm39) V1320I possibly damaging Het
Lrrc74a A G 12: 86,784,569 (GRCm39) H99R probably damaging Het
Me3 T A 7: 89,435,622 (GRCm39) probably null Het
Med13 T C 11: 86,219,987 (GRCm39) probably benign Het
Myh6 A T 14: 55,185,804 (GRCm39) Y1490* probably null Het
Myo10 T C 15: 25,804,454 (GRCm39) L1583P probably damaging Het
Nkx6-3 A G 8: 23,647,722 (GRCm39) E227G possibly damaging Het
Nlrp1a T A 11: 71,004,830 (GRCm39) probably benign Het
Nlrp5-ps A C 7: 14,317,016 (GRCm39) noncoding transcript Het
Nup188 T G 2: 30,216,491 (GRCm39) I765S probably null Het
Obscn G A 11: 59,019,107 (GRCm39) A969V probably benign Het
Or11a4 T C 17: 37,536,934 (GRCm39) L306P possibly damaging Het
Or1j19 T A 2: 36,677,452 (GRCm39) M305K probably benign Het
Or5a1 G T 19: 12,097,217 (GRCm39) D286E possibly damaging Het
Or8k33 A T 2: 86,384,123 (GRCm39) L115Q probably damaging Het
Otogl T A 10: 107,606,511 (GRCm39) probably benign Het
Pcnx3 G A 19: 5,715,611 (GRCm39) R1472W probably damaging Het
Plekha5 G A 6: 140,537,473 (GRCm39) R646K possibly damaging Het
Plscr4 T A 9: 92,370,814 (GRCm39) probably benign Het
Pon2 G A 6: 5,266,156 (GRCm39) Q288* probably null Het
Ptpn13 C A 5: 103,681,214 (GRCm39) R805S probably damaging Het
Pyroxd2 A T 19: 42,735,992 (GRCm39) V62D probably damaging Het
Rab37 G T 11: 115,047,790 (GRCm39) C44F probably damaging Het
Rbm44 T C 1: 91,080,069 (GRCm39) S52P probably benign Het
Rgl3 A G 9: 21,888,153 (GRCm39) W454R probably damaging Het
Rita1 A G 5: 120,747,837 (GRCm39) S154P probably benign Het
Scn5a T C 9: 119,351,665 (GRCm39) D772G probably damaging Het
Sec23ip G A 7: 128,363,129 (GRCm39) probably benign Het
Skic8 A T 9: 54,634,862 (GRCm39) probably benign Het
Slc23a1 T A 18: 35,756,032 (GRCm39) probably benign Het
Slco1a8 A C 6: 141,928,053 (GRCm39) probably benign Het
Taar6 C A 10: 23,861,046 (GRCm39) V167L probably benign Het
Tmcc3 T A 10: 94,414,407 (GRCm39) N36K probably benign Het
Tmem200c T A 17: 69,147,543 (GRCm39) V42E probably damaging Het
Trhde T C 10: 114,338,887 (GRCm39) probably benign Het
Tshz3 A G 7: 36,469,958 (GRCm39) E649G probably benign Het
Utp4 T C 8: 107,625,169 (GRCm39) probably benign Het
Vmn1r30 A G 6: 58,412,262 (GRCm39) V190A probably benign Het
Vmn1r35 A G 6: 66,655,827 (GRCm39) I281T probably damaging Het
Vmn1r58 G T 7: 5,413,329 (GRCm39) H300Q probably benign Het
Vmn1r84 A G 7: 12,095,799 (GRCm39) L286P probably damaging Het
Vmn2r54 A T 7: 12,349,576 (GRCm39) C669S probably damaging Het
Zfp623 T C 15: 75,820,510 (GRCm39) S489P probably benign Het
Other mutations in Sparcl1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00653:Sparcl1 APN 5 104,240,788 (GRCm39) missense probably benign 0.04
IGL01291:Sparcl1 APN 5 104,242,581 (GRCm39) missense possibly damaging 0.88
IGL01958:Sparcl1 APN 5 104,240,406 (GRCm39) missense probably benign 0.30
IGL02749:Sparcl1 APN 5 104,240,746 (GRCm39) missense possibly damaging 0.57
IGL03034:Sparcl1 APN 5 104,241,103 (GRCm39) missense probably damaging 0.96
ANU05:Sparcl1 UTSW 5 104,242,581 (GRCm39) missense possibly damaging 0.88
R0007:Sparcl1 UTSW 5 104,234,946 (GRCm39) missense probably damaging 1.00
R0007:Sparcl1 UTSW 5 104,234,946 (GRCm39) missense probably damaging 1.00
R0071:Sparcl1 UTSW 5 104,233,707 (GRCm39) nonsense probably null
R0071:Sparcl1 UTSW 5 104,233,707 (GRCm39) nonsense probably null
R0278:Sparcl1 UTSW 5 104,236,263 (GRCm39) missense probably benign 0.16
R0581:Sparcl1 UTSW 5 104,241,178 (GRCm39) missense probably damaging 0.99
R1755:Sparcl1 UTSW 5 104,240,690 (GRCm39) missense probably benign 0.12
R1807:Sparcl1 UTSW 5 104,233,627 (GRCm39) missense probably damaging 1.00
R1925:Sparcl1 UTSW 5 104,241,220 (GRCm39) missense probably benign 0.09
R2110:Sparcl1 UTSW 5 104,236,289 (GRCm39) missense probably damaging 1.00
R2112:Sparcl1 UTSW 5 104,236,289 (GRCm39) missense probably damaging 1.00
R2331:Sparcl1 UTSW 5 104,233,660 (GRCm39) missense probably damaging 1.00
R2567:Sparcl1 UTSW 5 104,232,954 (GRCm39) missense probably damaging 1.00
R3029:Sparcl1 UTSW 5 104,241,092 (GRCm39) missense possibly damaging 0.59
R3104:Sparcl1 UTSW 5 104,241,203 (GRCm39) missense probably benign 0.00
R3106:Sparcl1 UTSW 5 104,241,203 (GRCm39) missense probably benign 0.00
R3979:Sparcl1 UTSW 5 104,240,647 (GRCm39) missense probably benign 0.00
R4772:Sparcl1 UTSW 5 104,236,356 (GRCm39) missense probably benign 0.15
R4967:Sparcl1 UTSW 5 104,240,776 (GRCm39) missense probably damaging 1.00
R5095:Sparcl1 UTSW 5 104,233,629 (GRCm39) missense probably damaging 1.00
R5103:Sparcl1 UTSW 5 104,233,629 (GRCm39) missense probably damaging 1.00
R5105:Sparcl1 UTSW 5 104,233,629 (GRCm39) missense probably damaging 1.00
R5140:Sparcl1 UTSW 5 104,233,629 (GRCm39) missense probably damaging 1.00
R5149:Sparcl1 UTSW 5 104,233,629 (GRCm39) missense probably damaging 1.00
R6245:Sparcl1 UTSW 5 104,233,013 (GRCm39) missense probably damaging 1.00
R6387:Sparcl1 UTSW 5 104,232,926 (GRCm39) missense probably damaging 1.00
R6544:Sparcl1 UTSW 5 104,240,310 (GRCm39) nonsense probably null
R6930:Sparcl1 UTSW 5 104,234,940 (GRCm39) missense probably damaging 1.00
R7246:Sparcl1 UTSW 5 104,233,023 (GRCm39) missense probably benign 0.00
R8490:Sparcl1 UTSW 5 104,233,574 (GRCm39) missense probably null 1.00
R8860:Sparcl1 UTSW 5 104,241,218 (GRCm39) missense probably benign 0.25
R8899:Sparcl1 UTSW 5 104,240,590 (GRCm39) missense probably benign 0.01
R9047:Sparcl1 UTSW 5 104,240,979 (GRCm39) missense possibly damaging 0.90
R9215:Sparcl1 UTSW 5 104,240,701 (GRCm39) missense probably benign 0.05
R9284:Sparcl1 UTSW 5 104,236,345 (GRCm39) nonsense probably null
R9424:Sparcl1 UTSW 5 104,241,030 (GRCm39) missense possibly damaging 0.91
R9622:Sparcl1 UTSW 5 104,234,998 (GRCm39) missense possibly damaging 0.62
Predicted Primers PCR Primer
(F):5'- TGCTGGTGGGAGGGACATACGC -3'
(R):5'- AATGATGCCAACAGTCTGTTTGACTGC -3'

Sequencing Primer
(F):5'- cccacctcccatccttagac -3'
(R):5'- CTGCGTGTTTAATACACAATTTCTC -3'
Protein Function and Prediction

Sparcl1 encodes Hevin/Sc1, an matricellular secreted glycoprotein in the SPARC family (1). Hevin has three major domains: an N-terminal acidic domain, a follistatin-like domain, and the extracellular calcium-binding domain (1). The follistain-like domain is homologous to a domain in follistatin, a protein that inhibits members of the TGF-β superfamily (1).  Hevin has been shown to inhibit the attachment and spreading of endothelial cells and to reduce focal adhesion formation by endothelial cells (2). Therefore, the proposed function of hevin is to modulate cell migration. Girard and Springer propose that hevin participates in lymphocyte transendothelial migration and might alter vascular permeability (2). The related protein, SPARC, functions as a cell cycle inhibitor, de-adhesive protein, a regulator of growth factor activity, and modulatory cell-matrix interactions (3).

Northern blot analysis detected expression of Sparcl1 in lymph node, brain, heart, lung, skeletal muscle, ovary, small intestine, and colon, with lower levels in placenta, pancreas, testis, spleen, and thymus, and no expression in kidney, liver, and peripheral blood leukocytes (4).

Sparcl1tm1Pmc/tm1Pmc; MGI:2153047

involves: 129S1/Sv

Homozygotes exhibit stunted and less branched processes extending from extending from Purkinje cell bodies compared to in wild-type mice and exhibit an increase in glial cells compared to in wild-type mice (5).

Sparcl1tm1Pmc/tm1Pmc; MGI:2153047

involves: 129S1/Sv * C57BL/6

Mice homozygous for a targeted null mutation exhibit no discernable phenotype; mice are viable and fertile with normal histology and survival (6).

References
Posted On 2013-04-24
Science Writer Anne Murray