Incidental Mutation 'R4364:Frem1'
ID 325666
Institutional Source Beutler Lab
Gene Symbol Frem1
Ensembl Gene ENSMUSG00000059049
Gene Name Fras1 related extracellular matrix protein 1
Synonyms eyes2, crf11, eye, QBRICK, heb
MMRRC Submission 041672-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.712) question?
Stock # R4364 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 82816157-82970576 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 82831488 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Asparagine at position 2043 (Y2043N)
Ref Sequence ENSEMBL: ENSMUSP00000071627 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000071708] [ENSMUST00000107230] [ENSMUST00000170248]
AlphaFold Q684R7
Predicted Effect probably damaging
Transcript: ENSMUST00000071708
AA Change: Y2043N

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000071627
Gene: ENSMUSG00000059049
AA Change: Y2043N

DomainStartEndE-ValueType
signal peptide 1 29 N/A INTRINSIC
Pfam:Cadherin_3 364 508 1.7e-37 PFAM
Pfam:Cadherin_3 509 623 3.7e-18 PFAM
Pfam:Cadherin_3 592 709 8.4e-16 PFAM
Pfam:Cadherin_3 746 894 4.8e-26 PFAM
Pfam:Cadherin_3 863 1009 2.8e-30 PFAM
Pfam:Cadherin_3 1024 1115 6.4e-13 PFAM
Pfam:Cadherin_3 1119 1252 1.4e-17 PFAM
Pfam:Cadherin_3 1243 1393 8.2e-35 PFAM
Pfam:Cadherin_3 1378 1506 2e-22 PFAM
Pfam:Cadherin_3 1506 1616 1e-29 PFAM
Pfam:Cadherin_3 1617 1744 1.5e-14 PFAM
Pfam:Calx-beta 1749 1848 2.6e-10 PFAM
low complexity region 1894 1910 N/A INTRINSIC
CLECT 2065 2188 2.25e-27 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000107230
AA Change: Y2024N

PolyPhen 2 Score 0.953 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000102849
Gene: ENSMUSG00000059049
AA Change: Y2024N

DomainStartEndE-ValueType
signal peptide 1 29 N/A INTRINSIC
internal_repeat_1 296 967 9.01e-39 PROSPERO
internal_repeat_1 1026 1705 9.01e-39 PROSPERO
Pfam:Calx-beta 1730 1829 6.7e-10 PFAM
low complexity region 1875 1891 N/A INTRINSIC
CLECT 2046 2169 2.25e-27 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130889
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133610
Predicted Effect probably benign
Transcript: ENSMUST00000170248
AA Change: Y2025N

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000125809
Gene: ENSMUSG00000059049
AA Change: Y2025N

DomainStartEndE-ValueType
signal peptide 1 29 N/A INTRINSIC
Pfam:Cadherin_3 365 509 1.3e-37 PFAM
Pfam:Cadherin_3 510 623 4.5e-18 PFAM
Pfam:Cadherin_3 593 711 6.1e-16 PFAM
Pfam:Cadherin_3 728 876 2.7e-27 PFAM
Pfam:Cadherin_3 845 991 2.1e-30 PFAM
Pfam:Cadherin_3 1006 1097 4.8e-13 PFAM
Pfam:Cadherin_3 1101 1234 1e-17 PFAM
Pfam:Cadherin_3 1225 1375 6.1e-35 PFAM
Pfam:Cadherin_3 1360 1488 1.5e-22 PFAM
Pfam:Cadherin_3 1488 1598 7.5e-30 PFAM
Pfam:Cadherin_3 1599 1726 1.1e-14 PFAM
Pfam:Calx-beta 1731 1830 6.4e-10 PFAM
low complexity region 1876 1892 N/A INTRINSIC
CLECT 2047 2170 2.25e-27 SMART
Meta Mutation Damage Score 0.2698 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 93.8%
Validation Efficiency 93% (40/43)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a basement membrane protein that may play a role in craniofacial and renal development. Mutations in this gene have been associated with bifid nose with or without anorectal and renal anomalies. Alternatively spliced transcript variants encoding different isoforms have been described. PubMed ID 19940113 describes one such variant that initiates transcription within a distinct, internal exon; the resulting shorter isoform (named Toll-like/interleukin-1 receptor regulator, TILRR) is suggested to be a co-receptor of the interleukin 1 receptor family and may regulate receptor function and Toll-like receptor/interleukin 1 receptor signal transduction, contributing to the control of inflammatory response activation. [provided by RefSeq, Apr 2011]
PHENOTYPE: Homozygous mutation of this gene results in subepidermal blistering, cryptophthalmos, syndactyly, and renal agenesis. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 34 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Amn A C 12: 111,238,196 (GRCm39) N37H probably damaging Het
Apoa5 A T 9: 46,181,827 (GRCm39) D301V probably damaging Het
Atrn A G 2: 130,812,128 (GRCm39) E691G probably benign Het
Ccer1 CGAGGAGGAGGAGGAGGAGGA CGAGGAGGAGGAGGAGGA 10: 97,530,232 (GRCm39) probably benign Het
Cct2 A G 10: 116,891,056 (GRCm39) V396A probably damaging Het
Dhx35 C T 2: 158,684,272 (GRCm39) Q516* probably null Het
Dop1b A G 16: 93,567,812 (GRCm39) K1413R probably benign Het
Dpp9 T C 17: 56,494,391 (GRCm39) H856R possibly damaging Het
Eif4e2 T C 1: 87,152,093 (GRCm39) F97L probably benign Het
Exoc6b A T 6: 84,980,161 (GRCm39) probably benign Het
Fat1 T A 8: 45,405,999 (GRCm39) S917T probably benign Het
Galnt14 A G 17: 73,819,154 (GRCm39) I312T probably damaging Het
Glipr1 T C 10: 111,821,542 (GRCm39) N220S possibly damaging Het
Grid1 A G 14: 34,667,989 (GRCm39) E172G probably benign Het
Hspa4l C A 3: 40,721,241 (GRCm39) probably null Het
Il1rl2 G T 1: 40,390,951 (GRCm39) R298L probably benign Het
Il7r T A 15: 9,513,014 (GRCm39) H165L probably damaging Het
Krt87 T G 15: 101,385,395 (GRCm39) M326L probably benign Het
Lcn10 G T 2: 25,574,052 (GRCm39) C85F probably damaging Het
Mideas C T 12: 84,203,245 (GRCm39) G886S probably benign Het
Nup205 C A 6: 35,168,962 (GRCm39) P397Q probably benign Het
Or4d10 A G 19: 12,051,861 (GRCm39) V45A probably benign Het
Or4f17-ps1 G A 2: 111,357,985 (GRCm39) V127M probably benign Het
Or8b12c A T 9: 37,715,486 (GRCm39) H93L probably benign Het
Prkce C T 17: 86,784,279 (GRCm39) T218I probably damaging Het
Rhbdl2 T A 4: 123,703,728 (GRCm39) M1K probably null Het
Ripor2 C T 13: 24,905,694 (GRCm39) P947S probably benign Het
Shoc1 T G 4: 59,082,294 (GRCm39) T445P possibly damaging Het
Shroom3 G T 5: 93,090,945 (GRCm39) V1151F probably damaging Het
Sptbn5 A G 2: 119,899,136 (GRCm39) L428P probably damaging Het
Syne1 A G 10: 5,303,987 (GRCm39) V789A probably damaging Het
Taar8c C T 10: 23,977,477 (GRCm39) V112M probably benign Het
Tex10 T C 4: 48,468,774 (GRCm39) I51V probably benign Het
Ttll1 T A 15: 83,384,195 (GRCm39) Q144L probably damaging Het
Other mutations in Frem1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00155:Frem1 APN 4 82,877,626 (GRCm39) missense possibly damaging 0.46
IGL01069:Frem1 APN 4 82,932,104 (GRCm39) missense probably benign 0.00
IGL01106:Frem1 APN 4 82,840,494 (GRCm39) missense probably benign 0.00
IGL01398:Frem1 APN 4 82,868,599 (GRCm39) missense possibly damaging 0.64
IGL01617:Frem1 APN 4 82,854,376 (GRCm39) missense probably benign 0.02
IGL01647:Frem1 APN 4 82,868,593 (GRCm39) missense possibly damaging 0.60
IGL01690:Frem1 APN 4 82,877,533 (GRCm39) splice site probably benign
IGL02006:Frem1 APN 4 82,911,037 (GRCm39) critical splice donor site probably null
IGL02069:Frem1 APN 4 82,821,788 (GRCm39) missense probably damaging 1.00
IGL02131:Frem1 APN 4 82,843,091 (GRCm39) missense probably benign 0.03
IGL02225:Frem1 APN 4 82,858,743 (GRCm39) missense probably damaging 1.00
IGL02439:Frem1 APN 4 82,874,582 (GRCm39) missense probably benign 0.00
IGL02567:Frem1 APN 4 82,918,292 (GRCm39) missense probably damaging 1.00
IGL02647:Frem1 APN 4 82,919,991 (GRCm39) missense probably damaging 1.00
IGL02653:Frem1 APN 4 82,877,571 (GRCm39) missense probably benign 0.22
IGL02831:Frem1 APN 4 82,874,395 (GRCm39) missense probably benign 0.31
IGL02997:Frem1 APN 4 82,853,205 (GRCm39) missense probably damaging 1.00
IGL03005:Frem1 APN 4 82,912,371 (GRCm39) missense probably damaging 1.00
IGL03036:Frem1 APN 4 82,877,576 (GRCm39) missense possibly damaging 0.55
IGL03193:Frem1 APN 4 82,912,263 (GRCm39) splice site probably benign
IGL03218:Frem1 APN 4 82,832,883 (GRCm39) missense probably benign 0.00
IGL03235:Frem1 APN 4 82,938,992 (GRCm39) missense possibly damaging 0.87
IGL03243:Frem1 APN 4 82,932,206 (GRCm39) missense probably damaging 1.00
bat UTSW 4 82,983,060 (GRCm38) intron probably benign
blister UTSW 4 82,939,007 (GRCm39) missense probably benign 0.28
boy UTSW 4 82,874,492 (GRCm39) missense probably benign 0.16
Bubblie UTSW 4 82,888,870 (GRCm39) critical splice donor site probably null
magicbear UTSW 4 82,920,057 (GRCm39) missense probably damaging 1.00
major UTSW 4 82,907,426 (GRCm39) missense probably damaging 1.00
R6324_Frem1_643 UTSW 4 82,901,574 (GRCm39) missense probably benign 0.00
PIT4131001:Frem1 UTSW 4 82,924,045 (GRCm39) missense probably damaging 0.99
PIT4466001:Frem1 UTSW 4 82,890,374 (GRCm39) missense probably benign 0.01
PIT4472001:Frem1 UTSW 4 82,890,374 (GRCm39) missense probably benign 0.01
PIT4515001:Frem1 UTSW 4 82,818,663 (GRCm39) missense probably damaging 0.98
PIT4531001:Frem1 UTSW 4 82,868,517 (GRCm39) missense probably benign 0.12
R0010:Frem1 UTSW 4 82,918,335 (GRCm39) missense probably benign 0.41
R0010:Frem1 UTSW 4 82,918,335 (GRCm39) missense probably benign 0.41
R0115:Frem1 UTSW 4 82,854,406 (GRCm39) missense possibly damaging 0.94
R0125:Frem1 UTSW 4 82,930,188 (GRCm39) missense probably damaging 1.00
R0280:Frem1 UTSW 4 82,887,681 (GRCm39) missense probably damaging 1.00
R0504:Frem1 UTSW 4 82,830,874 (GRCm39) missense probably benign 0.26
R0519:Frem1 UTSW 4 82,888,870 (GRCm39) critical splice donor site probably null
R0631:Frem1 UTSW 4 82,890,402 (GRCm39) missense probably damaging 1.00
R0645:Frem1 UTSW 4 82,907,403 (GRCm39) missense probably damaging 1.00
R0781:Frem1 UTSW 4 82,868,557 (GRCm39) missense probably damaging 0.99
R1110:Frem1 UTSW 4 82,868,557 (GRCm39) missense probably damaging 0.99
R1115:Frem1 UTSW 4 82,939,007 (GRCm39) missense probably benign 0.28
R1130:Frem1 UTSW 4 82,834,865 (GRCm39) splice site probably null
R1173:Frem1 UTSW 4 82,868,589 (GRCm39) missense probably benign 0.16
R1349:Frem1 UTSW 4 82,840,542 (GRCm39) splice site probably benign
R1464:Frem1 UTSW 4 82,930,116 (GRCm39) missense probably damaging 1.00
R1464:Frem1 UTSW 4 82,930,116 (GRCm39) missense probably damaging 1.00
R1658:Frem1 UTSW 4 82,920,045 (GRCm39) missense probably damaging 1.00
R1672:Frem1 UTSW 4 82,917,128 (GRCm39) missense probably benign 0.09
R1831:Frem1 UTSW 4 82,939,074 (GRCm39) missense possibly damaging 0.95
R1851:Frem1 UTSW 4 82,868,737 (GRCm39) missense probably damaging 0.98
R2014:Frem1 UTSW 4 82,924,089 (GRCm39) missense probably damaging 1.00
R2021:Frem1 UTSW 4 82,831,795 (GRCm39) missense probably benign 0.02
R2022:Frem1 UTSW 4 82,831,795 (GRCm39) missense probably benign 0.02
R2023:Frem1 UTSW 4 82,831,795 (GRCm39) missense probably benign 0.02
R2183:Frem1 UTSW 4 82,909,732 (GRCm39) missense probably benign 0.00
R2437:Frem1 UTSW 4 82,918,410 (GRCm39) missense probably damaging 1.00
R2520:Frem1 UTSW 4 82,868,527 (GRCm39) missense probably damaging 0.99
R3195:Frem1 UTSW 4 82,932,351 (GRCm39) missense probably damaging 0.99
R3196:Frem1 UTSW 4 82,932,351 (GRCm39) missense probably damaging 0.99
R3408:Frem1 UTSW 4 82,930,223 (GRCm39) missense probably damaging 1.00
R3411:Frem1 UTSW 4 82,881,416 (GRCm39) missense possibly damaging 0.51
R3742:Frem1 UTSW 4 82,930,104 (GRCm39) missense probably damaging 1.00
R3829:Frem1 UTSW 4 82,917,167 (GRCm39) missense probably damaging 1.00
R3888:Frem1 UTSW 4 82,831,844 (GRCm39) missense probably benign 0.41
R4329:Frem1 UTSW 4 82,904,774 (GRCm39) missense probably benign 0.01
R4411:Frem1 UTSW 4 82,881,481 (GRCm39) missense probably damaging 1.00
R4624:Frem1 UTSW 4 82,907,343 (GRCm39) missense probably damaging 1.00
R4687:Frem1 UTSW 4 82,938,868 (GRCm39) missense probably damaging 1.00
R4764:Frem1 UTSW 4 82,907,426 (GRCm39) missense probably damaging 1.00
R4801:Frem1 UTSW 4 82,834,865 (GRCm39) splice site probably benign
R4802:Frem1 UTSW 4 82,834,865 (GRCm39) splice site probably benign
R4854:Frem1 UTSW 4 82,834,995 (GRCm39) missense possibly damaging 0.88
R4872:Frem1 UTSW 4 82,881,387 (GRCm39) missense probably damaging 1.00
R4947:Frem1 UTSW 4 82,884,371 (GRCm39) missense probably damaging 0.99
R5007:Frem1 UTSW 4 82,859,049 (GRCm39) intron probably benign
R5103:Frem1 UTSW 4 82,909,849 (GRCm39) missense probably benign
R5369:Frem1 UTSW 4 82,919,976 (GRCm39) missense possibly damaging 0.61
R5494:Frem1 UTSW 4 82,858,990 (GRCm39) makesense probably null
R5694:Frem1 UTSW 4 82,912,353 (GRCm39) missense probably damaging 1.00
R5780:Frem1 UTSW 4 82,868,652 (GRCm39) missense probably benign 0.12
R5813:Frem1 UTSW 4 82,918,395 (GRCm39) missense probably damaging 1.00
R5843:Frem1 UTSW 4 82,854,289 (GRCm39) missense probably damaging 1.00
R5914:Frem1 UTSW 4 82,920,012 (GRCm39) missense probably damaging 1.00
R5985:Frem1 UTSW 4 82,884,287 (GRCm39) missense probably benign
R6091:Frem1 UTSW 4 82,818,796 (GRCm39) missense probably benign 0.01
R6165:Frem1 UTSW 4 82,874,492 (GRCm39) missense probably benign 0.16
R6324:Frem1 UTSW 4 82,901,574 (GRCm39) missense probably benign 0.00
R6369:Frem1 UTSW 4 82,832,029 (GRCm39) splice site probably null
R6414:Frem1 UTSW 4 82,858,773 (GRCm39) missense probably damaging 0.98
R6421:Frem1 UTSW 4 82,912,365 (GRCm39) missense probably damaging 1.00
R6434:Frem1 UTSW 4 82,884,253 (GRCm39) missense probably benign 0.03
R6453:Frem1 UTSW 4 82,833,062 (GRCm39) nonsense probably null
R6598:Frem1 UTSW 4 82,932,065 (GRCm39) missense probably damaging 0.99
R6720:Frem1 UTSW 4 82,932,069 (GRCm39) missense probably damaging 0.98
R6862:Frem1 UTSW 4 82,930,251 (GRCm39) nonsense probably null
R6922:Frem1 UTSW 4 82,840,506 (GRCm39) missense probably damaging 1.00
R6931:Frem1 UTSW 4 82,888,914 (GRCm39) missense probably damaging 1.00
R6992:Frem1 UTSW 4 82,858,599 (GRCm39) missense possibly damaging 0.62
R6995:Frem1 UTSW 4 82,904,838 (GRCm39) missense probably damaging 1.00
R7001:Frem1 UTSW 4 82,904,798 (GRCm39) missense probably benign 0.44
R7104:Frem1 UTSW 4 82,858,918 (GRCm39) missense probably benign 0.30
R7146:Frem1 UTSW 4 82,840,532 (GRCm39) missense possibly damaging 0.93
R7174:Frem1 UTSW 4 82,840,493 (GRCm39) missense probably benign 0.00
R7327:Frem1 UTSW 4 82,938,992 (GRCm39) missense possibly damaging 0.87
R7343:Frem1 UTSW 4 82,912,359 (GRCm39) missense probably damaging 0.99
R7368:Frem1 UTSW 4 82,884,381 (GRCm39) missense probably benign 0.19
R7392:Frem1 UTSW 4 82,932,064 (GRCm39) missense probably benign 0.06
R7465:Frem1 UTSW 4 82,833,072 (GRCm39) missense probably benign 0.11
R7499:Frem1 UTSW 4 82,924,007 (GRCm39) missense probably damaging 1.00
R7536:Frem1 UTSW 4 82,874,432 (GRCm39) missense probably damaging 1.00
R7752:Frem1 UTSW 4 82,877,614 (GRCm39) missense probably benign 0.02
R7753:Frem1 UTSW 4 82,832,217 (GRCm39) missense probably benign 0.03
R7790:Frem1 UTSW 4 82,907,401 (GRCm39) missense probably benign 0.02
R7818:Frem1 UTSW 4 82,932,245 (GRCm39) missense probably damaging 1.00
R7877:Frem1 UTSW 4 82,932,049 (GRCm39) critical splice donor site probably null
R7878:Frem1 UTSW 4 82,938,917 (GRCm39) missense probably benign 0.00
R7886:Frem1 UTSW 4 82,934,643 (GRCm39) missense possibly damaging 0.68
R7901:Frem1 UTSW 4 82,877,614 (GRCm39) missense probably benign 0.02
R7976:Frem1 UTSW 4 82,919,946 (GRCm39) missense probably damaging 0.97
R8240:Frem1 UTSW 4 82,874,485 (GRCm39) missense probably benign 0.21
R8305:Frem1 UTSW 4 82,918,226 (GRCm39) missense probably benign 0.06
R8415:Frem1 UTSW 4 82,918,499 (GRCm39) missense probably damaging 1.00
R8751:Frem1 UTSW 4 82,889,015 (GRCm39) missense probably damaging 1.00
R8819:Frem1 UTSW 4 82,821,754 (GRCm39) missense probably damaging 1.00
R8820:Frem1 UTSW 4 82,821,754 (GRCm39) missense probably damaging 1.00
R8829:Frem1 UTSW 4 82,918,431 (GRCm39) missense probably damaging 1.00
R8834:Frem1 UTSW 4 82,922,610 (GRCm39) missense probably damaging 1.00
R8857:Frem1 UTSW 4 82,922,280 (GRCm39) intron probably benign
R8910:Frem1 UTSW 4 82,868,694 (GRCm39) missense probably benign 0.09
R9036:Frem1 UTSW 4 82,831,785 (GRCm39) missense probably benign
R9228:Frem1 UTSW 4 82,920,057 (GRCm39) missense probably damaging 1.00
R9382:Frem1 UTSW 4 82,901,622 (GRCm39) missense possibly damaging 0.79
R9441:Frem1 UTSW 4 82,924,083 (GRCm39) missense probably damaging 1.00
R9492:Frem1 UTSW 4 82,920,057 (GRCm39) missense probably damaging 1.00
R9517:Frem1 UTSW 4 82,901,714 (GRCm39) missense probably damaging 1.00
R9640:Frem1 UTSW 4 82,831,896 (GRCm39) missense probably benign
R9641:Frem1 UTSW 4 82,877,653 (GRCm39) missense probably damaging 1.00
X0013:Frem1 UTSW 4 82,833,045 (GRCm39) missense probably benign 0.38
X0017:Frem1 UTSW 4 82,909,870 (GRCm39) critical splice acceptor site probably null
Z1088:Frem1 UTSW 4 82,890,504 (GRCm39) missense probably damaging 1.00
Z1176:Frem1 UTSW 4 82,918,220 (GRCm39) missense probably damaging 1.00
Z1177:Frem1 UTSW 4 82,918,506 (GRCm39) missense probably benign 0.39
Z1177:Frem1 UTSW 4 82,858,552 (GRCm39) critical splice donor site probably null
Z1177:Frem1 UTSW 4 82,934,701 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- AAAGTCACTTCGTACCATGTTTCC -3'
(R):5'- CAAAATGGACCCCAAGTTGG -3'

Sequencing Primer
(F):5'- ATGTTTCCCTCATGGCTTTCTAGG -3'
(R):5'- GGACAGTTTACTTGACACAGATG -3'
Posted On 2015-07-06