Incidental Mutation 'R5088:Il6st'
ID 387594
Institutional Source Beutler Lab
Gene Symbol Il6st
Ensembl Gene ENSMUSG00000021756
Gene Name interleukin 6 signal transducer
Synonyms 5133400A03Rik, CD130, gp130, D13Ertd699e
MMRRC Submission 042677-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5088 (G1)
Quality Score 225
Status Validated
Chromosome 13
Chromosomal Location 112600604-112643394 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 112627089 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Methionine at position 294 (V294M)
Ref Sequence ENSEMBL: ENSMUSP00000139311 (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: V294M

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000064205
Gene: ENSMUSG00000021756
AA Change: V294M

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: V294M

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000138836
Gene: ENSMUSG00000021756
AA Change: V294M

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 damaging
Transcript: ENSMUST00000183829
AA Change: V130M

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000138987
Gene: ENSMUSG00000021756
AA Change: V130M

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 damaging
Transcript: ENSMUST00000184276
AA Change: V294M

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000139060
Gene: ENSMUSG00000021756
AA Change: V294M

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: V294M

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000139227
Gene: ENSMUSG00000021756
AA Change: V294M

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 damaging
Transcript: ENSMUST00000184445
AA Change: V294M

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000139311
Gene: ENSMUSG00000021756
AA Change: V294M

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 possibly damaging
Transcript: ENSMUST00000184949
AA Change: V294M

PolyPhen 2 Score 0.839 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000138915
Gene: ENSMUSG00000021756
AA Change: V294M

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
Meta Mutation Damage Score 0.1433 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 93.9%
Validation Efficiency 99% (72/73)
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: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930522L14Rik A T 5: 109,883,939 (GRCm39) C640S probably damaging Het
4931429L15Rik T C 9: 46,217,038 (GRCm39) R246G probably benign Het
Aak1 T C 6: 86,921,462 (GRCm39) probably null Het
Abcc5 A G 16: 20,195,412 (GRCm39) L695P probably damaging Het
Alcam T A 16: 52,109,290 (GRCm39) T328S probably damaging Het
Alpk1 A G 3: 127,478,969 (GRCm39) probably benign Het
Arel1 A G 12: 84,970,889 (GRCm39) L642P probably damaging Het
Atrip T C 9: 108,888,964 (GRCm39) D741G probably damaging Het
Bmp1 T C 14: 70,723,659 (GRCm39) T726A possibly damaging Het
Bnip3 A G 7: 138,496,337 (GRCm39) probably null Het
Cacng5 C G 11: 107,768,215 (GRCm39) C264S possibly damaging Het
Calr4 T A 4: 109,101,859 (GRCm39) probably benign Het
Cdhr1 T A 14: 36,811,422 (GRCm39) T230S probably benign Het
Cdk16 T C X: 20,562,566 (GRCm39) probably benign Het
Cenpj T C 14: 56,791,148 (GRCm39) E337G probably damaging Het
Chd9 A G 8: 91,704,147 (GRCm39) I694V possibly damaging Het
Chsy3 T A 18: 59,312,607 (GRCm39) V360D probably damaging Het
Col16a1 C T 4: 129,972,988 (GRCm39) T643M probably benign Het
Col5a1 G A 2: 27,908,614 (GRCm39) W67* probably null Het
Cyp20a1 A T 1: 60,402,509 (GRCm39) H198L probably damaging Het
Dnai1 T A 4: 41,597,630 (GRCm39) S38T probably benign Het
Dnai1 T G 4: 41,632,251 (GRCm39) S562A probably benign Het
Dpy19l4 G T 4: 11,303,357 (GRCm39) T188K probably damaging Het
Ergic2 A G 6: 148,084,621 (GRCm39) V304A probably damaging Het
Fam83a A G 15: 57,873,196 (GRCm39) T342A probably benign Het
Fbxo7 A G 10: 85,857,784 (GRCm39) probably benign Het
Gins4 T C 8: 23,727,084 (GRCm39) E3G possibly damaging Het
Glis3 G A 19: 28,508,979 (GRCm39) P335L probably benign Het
Golph3l A T 3: 95,524,501 (GRCm39) T251S possibly damaging Het
Hnf4g C T 3: 3,722,181 (GRCm39) A445V probably benign Het
Hykk A G 9: 54,853,763 (GRCm39) I362V probably benign Het
Itpr1 A G 6: 108,366,348 (GRCm39) I92V probably damaging Het
Kdm4c T C 4: 74,252,936 (GRCm39) L501P probably benign Het
Mpi G A 9: 57,457,887 (GRCm39) T105M probably damaging Het
Mrpl37 A T 4: 106,921,919 (GRCm39) L132H probably damaging Het
Muc5ac A T 7: 141,350,056 (GRCm39) T600S possibly damaging Het
Npl A T 1: 153,384,890 (GRCm39) I249N possibly damaging Het
Or10j27 C T 1: 172,958,606 (GRCm39) M59I probably damaging Het
Or7g30 A G 9: 19,353,067 (GRCm39) N286S probably damaging Het
Pkd1 A G 17: 24,809,812 (GRCm39) K3497E possibly damaging Het
Ptprt T C 2: 162,080,095 (GRCm39) N235D probably benign Het
Rangap1 A C 15: 81,594,664 (GRCm39) D388E probably benign Het
Rcvrn A T 11: 67,586,340 (GRCm39) Q33L probably benign Het
Rif1 A T 2: 51,982,307 (GRCm39) K524I possibly damaging Het
Rnf139 A T 15: 58,771,790 (GRCm39) N605I possibly damaging Het
Ryr2 C A 13: 11,727,129 (GRCm39) G2411* probably null Het
Scn3a A T 2: 65,302,643 (GRCm39) S1268T probably damaging Het
Sema6a T A 18: 47,382,196 (GRCm39) I784F probably damaging Het
Sgms2 C T 3: 131,124,005 (GRCm39) V232M probably benign Het
Skint7 T C 4: 111,837,627 (GRCm39) I135T possibly damaging Het
Smchd1 A T 17: 71,738,343 (GRCm39) N507K possibly damaging Het
Spata31d1a A C 13: 59,848,966 (GRCm39) probably null Het
Spata7 A T 12: 98,635,761 (GRCm39) D527V probably benign Het
Srcap A G 7: 127,140,833 (GRCm39) T1477A probably benign Het
Srl C A 16: 4,300,633 (GRCm39) D375Y probably damaging Het
Stk4 A T 2: 163,925,608 (GRCm39) K58* probably null Het
Svep1 T G 4: 58,120,648 (GRCm39) H795P possibly damaging Het
Trak2 T A 1: 58,974,967 (GRCm39) Q75L probably benign Het
Ubxn2a T A 12: 4,933,904 (GRCm39) N169I probably damaging Het
Vmn1r216 T A 13: 23,283,473 (GRCm39) L52* probably null Het
Vmn2r108 A T 17: 20,690,454 (GRCm39) N459K possibly damaging Het
Vstm5 A G 9: 15,168,601 (GRCm39) D55G possibly damaging Het
Wdr24 T A 17: 26,047,181 (GRCm39) probably null Het
Zfp13 C A 17: 23,796,035 (GRCm39) E179* probably null Het
Zfp839 T C 12: 110,834,610 (GRCm39) S546P probably damaging 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
R4899:Il6st UTSW 13 112,637,695 (GRCm39) missense probably damaging 1.00
R4922:Il6st UTSW 13 112,639,399 (GRCm39) missense probably damaging 0.98
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'- GCATGAGTCATCGCTTTCTCG -3'
(R):5'- ACATGTACAGCAGTGAGGGC -3'

Sequencing Primer
(F):5'- CCTGAGTATTGCAGGTCTCATAGAAG -3'
(R):5'- TGAGGGCAACATAATCCGC -3'
Posted On 2016-06-06