Incidental Mutation 'R0021:Map2k4'
ID 218438
Institutional Source Beutler Lab
Gene Symbol Map2k4
Ensembl Gene ENSMUSG00000033352
Gene Name mitogen-activated protein kinase kinase 4
Synonyms Serk1, Sek1, JNKK1, MKK4
MMRRC Submission 038316-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0021 (G1)
Quality Score 46
Status Validated
Chromosome 11
Chromosomal Location 65579069-65679123 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 65603110 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 174 (I174T)
Ref Sequence ENSEMBL: ENSMUSP00000041282 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000046963] [ENSMUST00000125598] [ENSMUST00000130009] [ENSMUST00000140301] [ENSMUST00000152096]
AlphaFold P47809
Predicted Effect probably damaging
Transcript: ENSMUST00000046963
AA Change: I174T

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000041282
Gene: ENSMUSG00000033352
AA Change: I174T

DomainStartEndE-ValueType
low complexity region 2 28 N/A INTRINSIC
S_TKc 100 365 9.38e-79 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000125598
SMART Domains Protein: ENSMUSP00000137656
Gene: ENSMUSG00000033352

DomainStartEndE-ValueType
Pfam:Pkinase 34 128 8.4e-27 PFAM
Pfam:Kinase-like 36 128 8.9e-8 PFAM
Pfam:Pkinase_Tyr 37 129 6.3e-17 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000130009
SMART Domains Protein: ENSMUSP00000137819
Gene: ENSMUSG00000033352

DomainStartEndE-ValueType
low complexity region 2 28 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000140301
SMART Domains Protein: ENSMUSP00000137955
Gene: ENSMUSG00000033352

DomainStartEndE-ValueType
low complexity region 2 28 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000152096
AA Change: I185T

PolyPhen 2 Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000114219
Gene: ENSMUSG00000033352
AA Change: I185T

DomainStartEndE-ValueType
low complexity region 2 28 N/A INTRINSIC
Pfam:Pkinase_Tyr 111 202 2.5e-9 PFAM
Pfam:Pkinase 111 204 1e-13 PFAM
Meta Mutation Damage Score 0.9136 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.8%
  • 10x: 97.6%
  • 20x: 95.8%
Validation Efficiency 97% (60/62)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
PHENOTYPE: Homozygotes for targeted null mutations exhibit abnormal liver development with a deficiency of parenchymal hepatocytes, severe anemia, and lethality before embryonic day 14.0. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 36 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310016G11Rik A G 7: 44,326,620 (GRCm39) noncoding transcript Het
Abcc5 T A 16: 20,197,411 (GRCm39) K647* probably null Het
Aplp1 A G 7: 30,135,241 (GRCm39) probably benign Het
Arhgef25 A G 10: 127,025,423 (GRCm39) I43T probably benign Het
Brinp3 T G 1: 146,777,189 (GRCm39) S545R probably benign Het
Btnl1 A G 17: 34,598,468 (GRCm39) E28G probably benign Het
C5ar2 A G 7: 15,971,601 (GRCm39) F109L probably benign Het
D630045J12Rik G A 6: 38,160,902 (GRCm39) Q1081* probably null Het
Dhx36 T C 3: 62,385,016 (GRCm39) I699V possibly damaging Het
Dnah9 A G 11: 65,860,805 (GRCm39) I2855T probably benign Het
Dock8 T C 19: 25,140,411 (GRCm39) I1317T probably benign Het
Galnt11 A T 5: 25,453,855 (GRCm39) D27V probably damaging Het
Gm5134 T A 10: 75,829,718 (GRCm39) C335S probably damaging Het
Hdhd2 A T 18: 77,058,311 (GRCm39) K227N probably damaging Het
Impg1 A T 9: 80,317,479 (GRCm39) L36Q probably damaging Het
Krtcap3 A G 5: 31,410,303 (GRCm39) H227R probably benign Het
Lrrc7 A G 3: 157,866,298 (GRCm39) Y1148H probably damaging Het
Mef2c C A 13: 83,804,359 (GRCm39) L282M probably damaging Het
Nkapd1 A C 9: 50,521,725 (GRCm39) D65E probably damaging Het
Nqo2 T C 13: 34,165,490 (GRCm39) I129T probably benign Het
Pdgfrb T A 18: 61,197,998 (GRCm39) probably benign Het
Phf7 C T 14: 30,960,443 (GRCm39) probably benign Het
Plac8 T A 5: 100,704,434 (GRCm39) T88S probably benign Het
Pou2f1 G A 1: 165,703,587 (GRCm39) T654M probably damaging Het
Ptprk T A 10: 28,468,891 (GRCm39) V1425E probably damaging Het
Saal1 A T 7: 46,342,316 (GRCm39) S376T probably damaging Het
Scart2 G A 7: 139,876,310 (GRCm39) R594H probably benign Het
Serpini1 T C 3: 75,526,620 (GRCm39) Y291H probably damaging Het
Siah2 T C 3: 58,583,713 (GRCm39) H191R probably benign Het
Spaca6 T A 17: 18,058,498 (GRCm39) Y39* probably null Het
Tbc1d10a T C 11: 4,163,680 (GRCm39) C277R probably damaging Het
Trim45 A T 3: 100,832,736 (GRCm39) D323V probably damaging Het
Trim55 A C 3: 19,698,866 (GRCm39) M32L probably benign Het
Unc5b T C 10: 60,614,698 (GRCm39) T200A probably benign Het
Uqcc4 A G 17: 25,403,957 (GRCm39) E99G possibly damaging Het
V1rd19 A T 7: 23,703,029 (GRCm39) D165V probably damaging Het
Other mutations in Map2k4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00534:Map2k4 APN 11 65,610,305 (GRCm39) splice site probably benign
IGL01318:Map2k4 APN 11 65,647,089 (GRCm39) splice site probably benign
IGL02500:Map2k4 APN 11 65,587,136 (GRCm39) missense probably damaging 1.00
IGL02628:Map2k4 APN 11 65,581,567 (GRCm39) missense possibly damaging 0.83
IGL02873:Map2k4 APN 11 65,610,400 (GRCm39) missense probably damaging 0.97
IGL03124:Map2k4 APN 11 65,581,617 (GRCm39) missense probably damaging 0.98
R0021:Map2k4 UTSW 11 65,603,110 (GRCm39) missense probably damaging 1.00
R0034:Map2k4 UTSW 11 65,610,437 (GRCm39) splice site probably benign
R0034:Map2k4 UTSW 11 65,610,437 (GRCm39) splice site probably benign
R0646:Map2k4 UTSW 11 65,603,101 (GRCm39) missense probably damaging 1.00
R2073:Map2k4 UTSW 11 65,584,282 (GRCm39) missense probably damaging 0.99
R2931:Map2k4 UTSW 11 65,647,163 (GRCm39) missense probably damaging 0.99
R3800:Map2k4 UTSW 11 65,581,607 (GRCm39) nonsense probably null
R4820:Map2k4 UTSW 11 65,587,201 (GRCm39) splice site probably benign
R4913:Map2k4 UTSW 11 65,600,758 (GRCm39) missense probably damaging 1.00
R5452:Map2k4 UTSW 11 65,610,413 (GRCm39) missense probably damaging 0.97
R5497:Map2k4 UTSW 11 65,626,031 (GRCm39) missense probably damaging 1.00
R5812:Map2k4 UTSW 11 65,626,031 (GRCm39) missense probably damaging 1.00
R5976:Map2k4 UTSW 11 65,600,778 (GRCm39) missense probably benign 0.31
R6282:Map2k4 UTSW 11 65,597,842 (GRCm39) missense possibly damaging 0.78
R6505:Map2k4 UTSW 11 65,584,355 (GRCm39) missense possibly damaging 0.63
R6784:Map2k4 UTSW 11 65,582,577 (GRCm39) unclassified probably benign
R7560:Map2k4 UTSW 11 65,666,583 (GRCm39) missense unknown
R8071:Map2k4 UTSW 11 65,597,827 (GRCm39) missense
R9092:Map2k4 UTSW 11 65,581,599 (GRCm39) missense probably benign
R9342:Map2k4 UTSW 11 65,581,569 (GRCm39) missense probably benign
Predicted Primers PCR Primer
(F):5'- GGCACTCTGGTAAATGCAAACTGGTC -3'
(R):5'- TCACAAGCTAAAGGTTCAGCAGAGG -3'

Sequencing Primer
(F):5'- GGCACAGACATGGCTTTATC -3'
(R):5'- GCTAAAGGTTCAGCAGAGGTTTTAC -3'
Posted On 2014-08-08