Incidental Mutation 'R4899:Il6st'
ID 376034
Institutional Source Beutler Lab
Gene Symbol Il6st
Ensembl Gene ENSMUSG00000021756
Gene Name interleukin 6 signal transducer
Synonyms 5133400A03Rik, CD130, gp130, D13Ertd699e
MMRRC Submission 042503-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4899 (G1)
Quality Score 225
Status Not validated
Chromosome 13
Chromosomal Location 112600604-112643394 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 112637695 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Proline at position 628 (L628P)
Ref Sequence ENSEMBL: ENSMUSP00000139227 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000070731] [ENSMUST00000183513] [ENSMUST00000183663] [ENSMUST00000183829] [ENSMUST00000184276] [ENSMUST00000184311] [ENSMUST00000184445] [ENSMUST00000184949]
AlphaFold Q00560
Predicted Effect probably damaging
Transcript: ENSMUST00000070731
AA Change: L628P

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000064205
Gene: ENSMUSG00000021756
AA Change: L628P

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:Lep_receptor_Ig 26 112 1.4e-30 PFAM
FN3 126 205 1.15e1 SMART
FN3 220 306 7.23e-8 SMART
FN3 324 407 1.07e1 SMART
FN3 422 503 6.1e0 SMART
FN3 517 600 4.81e-4 SMART
transmembrane domain 618 640 N/A INTRINSIC
low complexity region 718 753 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000183513
SMART Domains Protein: ENSMUSP00000139016
Gene: ENSMUSG00000021756

DomainStartEndE-ValueType
signal peptide 1 23 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000183663
AA Change: L628P

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000138836
Gene: ENSMUSG00000021756
AA Change: L628P

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:Lep_receptor_Ig 24 114 1.2e-32 PFAM
FN3 126 205 1.15e1 SMART
FN3 220 306 7.23e-8 SMART
FN3 324 407 1.07e1 SMART
FN3 422 503 6.1e0 SMART
FN3 517 600 4.81e-4 SMART
transmembrane domain 618 640 N/A INTRINSIC
low complexity region 718 753 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000183829
SMART Domains Protein: ENSMUSP00000138987
Gene: ENSMUSG00000021756

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
PDB:1I1R|A 23 52 7e-8 PDB
FN3 56 142 7.23e-8 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000184276
SMART Domains Protein: ENSMUSP00000139060
Gene: ENSMUSG00000021756

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:Lep_receptor_Ig 24 114 2.3e-33 PFAM
FN3 126 205 1.15e1 SMART
FN3 220 306 7.23e-8 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000184311
AA Change: L628P

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000139227
Gene: ENSMUSG00000021756
AA Change: L628P

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:Lep_receptor_Ig 24 114 1.2e-32 PFAM
FN3 126 205 1.15e1 SMART
FN3 220 306 7.23e-8 SMART
FN3 324 407 1.07e1 SMART
FN3 422 503 6.1e0 SMART
FN3 517 600 4.81e-4 SMART
transmembrane domain 618 640 N/A INTRINSIC
low complexity region 718 753 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000184445
SMART Domains Protein: ENSMUSP00000139311
Gene: ENSMUSG00000021756

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:Lep_receptor_Ig 24 114 2e-33 PFAM
FN3 126 205 1.15e1 SMART
FN3 220 306 7.23e-8 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000184949
AA Change: L567P

PolyPhen 2 Score 0.969 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000138915
Gene: ENSMUSG00000021756
AA Change: L567P

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:Lep_receptor_Ig 24 114 9.4e-33 PFAM
FN3 126 205 1.15e1 SMART
FN3 220 306 7.23e-8 SMART
FN3 324 442 6.97e0 SMART
FN3 456 539 4.81e-4 SMART
transmembrane domain 557 579 N/A INTRINSIC
low complexity region 657 692 N/A INTRINSIC
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.7%
  • 20x: 93.7%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygotes for targeted null mutations show myocardial and hematological defects and die between embryonic day 12.5 and term. Conditional mutants show female infertility and neurological, cardiac, hematopoietic, immunological, hepatic, and lung defects. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abhd18 C G 3: 40,860,304 (GRCm39) probably null Het
Adra2c A T 5: 35,437,705 (GRCm39) Y159F probably damaging Het
Alkal2 T A 12: 30,934,972 (GRCm39) S64T probably benign Het
Apbb1ip T C 2: 22,713,361 (GRCm39) V72A unknown Het
Atp13a5 A G 16: 29,197,318 (GRCm39) L13P probably damaging Het
Azin2 G A 4: 128,828,446 (GRCm39) P254S probably benign Het
Bmpr1b T C 3: 141,546,444 (GRCm39) R481G probably damaging Het
Cacna2d4 G A 6: 119,245,157 (GRCm39) W288* probably null Het
Cass4 A G 2: 172,269,789 (GRCm39) T626A probably benign Het
Cep112 T A 11: 108,497,110 (GRCm39) D683E probably damaging Het
Cfap300 A T 9: 8,022,494 (GRCm39) S243T possibly damaging Het
Chat G T 14: 32,170,934 (GRCm39) S188R possibly damaging Het
Cit A G 5: 116,001,087 (GRCm39) Y162C possibly damaging Het
Clca3a1 T A 3: 144,443,722 (GRCm39) Y676F probably damaging Het
Clec2h A G 6: 128,652,787 (GRCm39) N185D probably benign Het
Cnbd2 G T 2: 156,181,141 (GRCm39) V192F probably benign Het
Col6a3 C A 1: 90,730,149 (GRCm39) G1112V probably damaging Het
Csta2 A T 16: 36,077,731 (GRCm39) Y96F possibly damaging Het
Cyp3a25 A G 5: 145,914,481 (GRCm39) F483S possibly damaging Het
Dscam T C 16: 96,485,018 (GRCm39) E1103G probably benign Het
Dync2h1 G A 9: 7,131,921 (GRCm39) Q1629* probably null Het
Enpp6 A G 8: 47,440,118 (GRCm39) Y38C probably damaging Het
Epg5 T A 18: 78,028,272 (GRCm39) L1271Q probably damaging Het
Fam47e G A 5: 92,722,528 (GRCm39) V75I probably benign Het
Fat3 T C 9: 15,881,095 (GRCm39) D3259G probably damaging Het
Fbxw28 T C 9: 109,159,921 (GRCm39) D211G probably damaging Het
Flnc A G 6: 29,446,842 (GRCm39) N990D probably benign Het
Frat1 T G 19: 41,818,761 (GRCm39) L52R probably damaging Het
Ftmt C G 18: 52,464,658 (GRCm39) probably benign Het
H2-M1 C T 17: 36,982,112 (GRCm39) G163D probably benign Het
Hapln1 A G 13: 89,749,769 (GRCm39) K105E possibly damaging Het
Igkv17-127 G T 6: 67,838,381 (GRCm39) A31S probably benign Het
Kcnj6 A G 16: 94,633,472 (GRCm39) I213T probably damaging Het
Kidins220 T C 12: 25,063,442 (GRCm39) probably null Het
Lama2 TTTGCGCATT TTT 10: 26,919,639 (GRCm39) probably null Het
Llgl1 C T 11: 60,600,394 (GRCm39) P581L probably benign Het
Mertk C A 2: 128,625,845 (GRCm39) P660Q probably damaging Het
Mrtfa A G 15: 80,902,587 (GRCm39) Y241H probably damaging Het
Mtarc2 A T 1: 184,577,821 (GRCm39) I65N probably damaging Het
Napepld A G 5: 21,888,438 (GRCm39) Y4H probably benign Het
Ncam1 T A 9: 49,456,551 (GRCm39) probably null Het
Nuak2 A T 1: 132,252,724 (GRCm39) K93* probably null Het
Oat A T 7: 132,165,951 (GRCm39) D211E probably benign Het
Or1j19 A G 2: 36,676,810 (GRCm39) Q91R probably benign Het
Or2aj6 G A 16: 19,442,950 (GRCm39) A300V probably benign Het
Or4c109 A C 2: 88,818,454 (GRCm39) L31V probably null Het
Or51b17 A G 7: 103,542,672 (GRCm39) I90T possibly damaging Het
Or7a39 A T 10: 78,715,041 (GRCm39) S12C probably benign Het
Pde4dip C A 3: 97,616,874 (GRCm39) K1789N probably damaging Het
Piezo2 T C 18: 63,211,862 (GRCm39) I1322V possibly damaging Het
Pih1d1 A G 7: 44,803,951 (GRCm39) probably benign Het
Plekhd1 T C 12: 80,769,101 (GRCm39) S454P probably damaging Het
Polr2h G A 16: 20,539,303 (GRCm39) V89M probably damaging Het
Pptc7 G A 5: 122,422,780 (GRCm39) G17S possibly damaging Het
Pramel55 T C 5: 95,949,586 (GRCm39) V111A probably benign Het
Ptpra T C 2: 130,386,356 (GRCm39) V602A probably damaging Het
Rnf123 C T 9: 107,940,879 (GRCm39) R654H probably damaging Het
Rufy4 T C 1: 74,186,822 (GRCm39) C537R probably damaging Het
Samsn1 A G 16: 75,675,991 (GRCm39) S135P probably damaging Het
Sgsm3 A G 15: 80,890,980 (GRCm39) N147S probably benign Het
Shoc1 T C 4: 59,062,640 (GRCm39) Y872C probably damaging Het
Slc22a29 T C 19: 8,138,933 (GRCm39) T510A probably benign Het
Smc4 T A 3: 68,939,144 (GRCm39) H978Q probably damaging Het
Sox7 G A 14: 64,185,927 (GRCm39) R321H probably damaging Het
Spred3 T C 7: 28,861,258 (GRCm39) D307G probably damaging Het
Syne2 T A 12: 75,900,875 (GRCm39) D11E probably benign Het
Tob1 ACAGCAGCAGCAGCAGCAGCAGCAGCA ACAGCAGCAGCAGCAGCAGCAGCA 11: 94,105,278 (GRCm39) probably benign Het
Top2b A T 14: 16,387,313 (GRCm38) I134F probably damaging Het
Tspan1 T A 4: 116,020,563 (GRCm39) R206* probably null Het
Ttc3 A T 16: 94,230,314 (GRCm39) N837I probably damaging Het
Vmn1r36 T C 6: 66,693,549 (GRCm39) T72A possibly damaging Het
Vmn2r10 A G 5: 109,151,324 (GRCm39) S97P probably damaging Het
Zfp2 T A 11: 50,790,841 (GRCm39) I401F probably damaging Het
Zfp629 T C 7: 127,210,190 (GRCm39) T540A possibly damaging Het
Zfr G A 15: 12,166,231 (GRCm39) V834I probably benign Het
Other mutations in Il6st
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00515:Il6st APN 13 112,617,967 (GRCm39) splice site probably null
IGL00571:Il6st APN 13 112,624,394 (GRCm39) missense probably damaging 1.00
IGL01151:Il6st APN 13 112,630,185 (GRCm39) missense probably benign 0.00
IGL01336:Il6st APN 13 112,616,773 (GRCm39) missense possibly damaging 0.71
IGL01501:Il6st APN 13 112,616,593 (GRCm39) missense probably benign 0.22
IGL01512:Il6st APN 13 112,640,900 (GRCm39) missense probably benign 0.36
IGL01657:Il6st APN 13 112,618,077 (GRCm39) missense probably damaging 1.00
IGL01863:Il6st APN 13 112,640,744 (GRCm39) missense possibly damaging 0.88
IGL01916:Il6st APN 13 112,616,606 (GRCm39) missense possibly damaging 0.90
IGL01978:Il6st APN 13 112,633,891 (GRCm39) missense possibly damaging 0.51
IGL02089:Il6st APN 13 112,631,774 (GRCm39) missense probably benign 0.12
IGL02752:Il6st APN 13 112,616,729 (GRCm39) missense probably damaging 0.98
IGL02988:Il6st UTSW 13 112,635,420 (GRCm39) missense probably damaging 1.00
R0019:Il6st UTSW 13 112,637,682 (GRCm39) missense possibly damaging 0.94
R0550:Il6st UTSW 13 112,611,648 (GRCm39) splice site probably null
R0606:Il6st UTSW 13 112,640,806 (GRCm39) missense possibly damaging 0.78
R1126:Il6st UTSW 13 112,640,266 (GRCm39) missense probably damaging 1.00
R1452:Il6st UTSW 13 112,617,998 (GRCm39) missense possibly damaging 0.79
R1581:Il6st UTSW 13 112,618,075 (GRCm39) missense probably damaging 0.99
R1632:Il6st UTSW 13 112,640,866 (GRCm39) missense possibly damaging 0.86
R1881:Il6st UTSW 13 112,640,947 (GRCm39) missense probably damaging 1.00
R2013:Il6st UTSW 13 112,635,423 (GRCm39) missense probably null 0.94
R2043:Il6st UTSW 13 112,616,753 (GRCm39) missense probably benign 0.00
R2128:Il6st UTSW 13 112,640,709 (GRCm39) missense probably benign 0.01
R2137:Il6st UTSW 13 112,639,392 (GRCm39) missense possibly damaging 0.92
R3433:Il6st UTSW 13 112,640,365 (GRCm39) missense probably damaging 1.00
R3696:Il6st UTSW 13 112,640,916 (GRCm39) missense probably benign 0.13
R3697:Il6st UTSW 13 112,640,916 (GRCm39) missense probably benign 0.13
R3698:Il6st UTSW 13 112,640,916 (GRCm39) missense probably benign 0.13
R4172:Il6st UTSW 13 112,631,861 (GRCm39) missense probably benign 0.25
R4543:Il6st UTSW 13 112,617,993 (GRCm39) missense probably damaging 1.00
R4641:Il6st UTSW 13 112,625,064 (GRCm39) missense probably damaging 1.00
R4838:Il6st UTSW 13 112,627,044 (GRCm39) nonsense probably null
R4922:Il6st UTSW 13 112,639,399 (GRCm39) missense probably damaging 0.98
R5088:Il6st UTSW 13 112,627,089 (GRCm39) missense probably damaging 1.00
R5104:Il6st UTSW 13 112,625,182 (GRCm39) missense probably benign 0.02
R5853:Il6st UTSW 13 112,618,071 (GRCm39) missense probably damaging 1.00
R6602:Il6st UTSW 13 112,640,947 (GRCm39) missense probably damaging 1.00
R7082:Il6st UTSW 13 112,640,566 (GRCm39) missense probably damaging 1.00
R7101:Il6st UTSW 13 112,631,907 (GRCm39) critical splice donor site probably null
R7192:Il6st UTSW 13 112,631,741 (GRCm39) missense probably benign 0.00
R7273:Il6st UTSW 13 112,631,832 (GRCm39) missense probably benign 0.37
R7330:Il6st UTSW 13 112,630,185 (GRCm39) missense probably benign 0.00
R7427:Il6st UTSW 13 112,625,094 (GRCm39) missense probably benign 0.01
R7770:Il6st UTSW 13 112,639,338 (GRCm39) missense probably damaging 1.00
R8086:Il6st UTSW 13 112,631,094 (GRCm39) splice site probably null
R8307:Il6st UTSW 13 112,624,281 (GRCm39) missense probably benign 0.16
R8831:Il6st UTSW 13 112,640,914 (GRCm39) missense probably damaging 1.00
R9041:Il6st UTSW 13 112,611,631 (GRCm39) missense probably benign 0.00
R9189:Il6st UTSW 13 112,635,340 (GRCm39) missense probably damaging 1.00
R9316:Il6st UTSW 13 112,639,349 (GRCm39) missense possibly damaging 0.95
R9409:Il6st UTSW 13 112,640,872 (GRCm39) missense probably benign 0.00
R9763:Il6st UTSW 13 112,627,051 (GRCm39) missense probably damaging 1.00
U24488:Il6st UTSW 13 112,631,168 (GRCm39) missense possibly damaging 0.90
Z1176:Il6st UTSW 13 112,630,152 (GRCm39) missense probably benign 0.01
Predicted Primers PCR Primer
(F):5'- GCAGGCACTTGGAAACAGAC -3'
(R):5'- ACCAAACAAGGGTGCTTTGG -3'

Sequencing Primer
(F):5'- TGACTGGGCTCCACAGTGAG -3'
(R):5'- CCAAACAAGGGTGCTTTGGTAGAAG -3'
Posted On 2016-03-17