Incidental Mutation 'R1509:Epha4'
ID 168105
Institutional Source Beutler Lab
Gene Symbol Epha4
Ensembl Gene ENSMUSG00000026235
Gene Name Eph receptor A4
Synonyms Tyro1, Sek1, rb, Sek, Cek8, 2900005C20Rik, Hek8
MMRRC Submission 039556-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.949) question?
Stock # R1509 (G1)
Quality Score 225
Status Validated
Chromosome 1
Chromosomal Location 77343822-77491725 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 77357523 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 825 (Y825C)
Ref Sequence ENSEMBL: ENSMUSP00000139640 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000027451] [ENSMUST00000187346] [ENSMUST00000188797] [ENSMUST00000188952] [ENSMUST00000190149]
AlphaFold Q03137
PDB Structure THE CRYSTAL STRUCTURE OF AN EPH RECEPTOR SAM DOMAIN REVEALS A MECHANISM FOR MODULAR DIMERIZATION. [X-RAY DIFFRACTION]
Crystal structure of a mutant EphA4 kinase domain (Y742A) [X-RAY DIFFRACTION]
Crystal structure of EphA4 kinase domain in complex with VUF 12058 [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF EPHA4 KINASE DOMAIN [X-RAY DIFFRACTION]
Crystal structure of EphA4 kinase domain in complex with Dasatinib. [X-RAY DIFFRACTION]
Predicted Effect probably damaging
Transcript: ENSMUST00000027451
AA Change: Y825C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000027451
Gene: ENSMUSG00000026235
AA Change: Y825C

DomainStartEndE-ValueType
EPH_lbd 30 204 1.35e-128 SMART
FN3 329 420 1.94e-8 SMART
FN3 441 522 9.18e-10 SMART
Pfam:EphA2_TM 548 618 1.7e-24 PFAM
TyrKc 621 878 1.91e-134 SMART
SAM 908 975 1.96e-20 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000187346
SMART Domains Protein: ENSMUSP00000140631
Gene: ENSMUSG00000026235

DomainStartEndE-ValueType
Pfam:Pkinase_Tyr 1 46 7.8e-10 PFAM
Pfam:SAM_2 76 117 4.8e-10 PFAM
Pfam:SAM_1 77 117 2.6e-9 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000188797
AA Change: Y825C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000140954
Gene: ENSMUSG00000026235
AA Change: Y825C

DomainStartEndE-ValueType
EPH_lbd 30 204 1.35e-128 SMART
FN3 329 420 1.94e-8 SMART
FN3 441 522 9.18e-10 SMART
Pfam:EphA2_TM 547 618 1.8e-27 PFAM
TyrKc 621 878 1.91e-134 SMART
SAM 908 975 1.96e-20 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000188952
AA Change: Y825C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000139640
Gene: ENSMUSG00000026235
AA Change: Y825C

DomainStartEndE-ValueType
EPH_lbd 30 204 1.35e-128 SMART
FN3 329 420 1.94e-8 SMART
FN3 441 522 9.18e-10 SMART
Pfam:EphA2_TM 547 618 1.8e-27 PFAM
TyrKc 621 878 1.91e-134 SMART
SAM 908 975 1.96e-20 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000190149
Meta Mutation Damage Score 0.9605 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.3%
  • 10x: 96.4%
  • 20x: 93.1%
Validation Efficiency 99% (89/90)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
PHENOTYPE: Mutants are known for their "hopping gait". Homozygotes for targeted null mutations show loss of limb alternation in locomotion and axon guidance defects of the corticospinal tract within medulla and spinal cord, resulting in aberrant midline projections. Heterozygotes show less severe phenotype. [provided by MGI curators]
Allele List at MGI

All alleles(66) : Targeted, knock-out(3) Targeted, other(9) Gene trapped(52) Spontaneous(2)

Other mutations in this stock
Total: 86 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2210408I21Rik T C 13: 77,340,766 (GRCm39) S132P probably benign Het
AC153895.1 T C 6: 50,020,451 (GRCm39) R54G unknown Het
Acot12 G A 13: 91,919,994 (GRCm39) probably null Het
Adhfe1 T A 1: 9,623,671 (GRCm39) D98E probably benign Het
Ago2 A G 15: 72,988,213 (GRCm39) F594S probably damaging Het
Aldh18a1 A G 19: 40,545,927 (GRCm39) I620T probably damaging Het
Aspscr1 C A 11: 120,592,342 (GRCm39) A294D probably damaging Het
Bod1l C G 5: 41,976,883 (GRCm39) R1477T probably damaging Het
Ccdc18 C A 5: 108,336,844 (GRCm39) A741D possibly damaging Het
Ces4a G A 8: 105,864,729 (GRCm39) G69S probably damaging Het
Cfap52 C T 11: 67,829,819 (GRCm39) V317I probably benign Het
Cgn A T 3: 94,681,568 (GRCm39) L509Q probably benign Het
Crb2 A G 2: 37,676,631 (GRCm39) H204R probably benign Het
Cspg4b A G 13: 113,504,790 (GRCm39) N431S probably damaging Het
Ddx39a G A 8: 84,446,527 (GRCm39) V99M probably damaging Het
Dis3l2 T A 1: 86,948,808 (GRCm39) C582S possibly damaging Het
Dmbt1 G A 7: 130,676,061 (GRCm39) probably benign Het
Dnah6 T C 6: 73,004,425 (GRCm39) E3846G probably damaging Het
Dstyk A G 1: 132,384,084 (GRCm39) E655G probably damaging Het
Esp36 T A 17: 38,728,173 (GRCm39) N36I probably damaging Het
Fabp3 C T 4: 130,206,180 (GRCm39) T57I probably benign Het
Fem1c A G 18: 46,657,280 (GRCm39) S145P probably benign Het
Galnt13 T C 2: 54,623,094 (GRCm39) I80T probably damaging Het
Gm5698 T C 1: 31,016,728 (GRCm39) T108A probably benign Het
Hipk3 A G 2: 104,271,607 (GRCm39) S442P probably benign Het
Hmcn2 T A 2: 31,204,491 (GRCm39) V22D possibly damaging Het
Hspg2 C T 4: 137,238,552 (GRCm39) probably benign Het
Ide A G 19: 37,262,603 (GRCm39) probably null Het
Ifnar1 C A 16: 91,300,384 (GRCm39) P462Q probably damaging Het
Itgb2l T A 16: 96,228,049 (GRCm39) I485F probably benign Het
Jakmip3 C T 7: 138,629,505 (GRCm39) R549W possibly damaging Het
Lrrc36 A G 8: 106,187,761 (GRCm39) Q680R probably damaging Het
Lysmd3 T G 13: 81,817,390 (GRCm39) H122Q probably benign Het
Macf1 C A 4: 123,577,802 (GRCm39) V61L possibly damaging Het
Map1b T C 13: 99,568,036 (GRCm39) T1562A unknown Het
Map3k20 A T 2: 72,194,968 (GRCm39) probably benign Het
Mroh8 A G 2: 157,075,125 (GRCm39) V457A probably benign Het
Mrpl40 T A 16: 18,694,159 (GRCm39) probably null Het
Ms4a10 C T 19: 10,941,472 (GRCm39) V166I probably benign Het
Mycl A G 4: 122,894,100 (GRCm39) D300G probably damaging Het
Naca T A 10: 127,879,266 (GRCm39) probably benign Het
Ncoa4 T C 14: 31,895,391 (GRCm39) S172P probably damaging Het
Nfatc3 T C 8: 106,810,486 (GRCm39) F421L possibly damaging Het
Nucb1 C A 7: 45,144,649 (GRCm39) K301N probably benign Het
Or1af1 A G 2: 37,109,966 (GRCm39) H155R probably damaging Het
Or52ae9 A T 7: 103,390,243 (GRCm39) M68K probably benign Het
Or5b99 T A 19: 12,976,815 (GRCm39) I155N possibly damaging Het
Panx1 A T 9: 14,921,341 (GRCm39) V178E possibly damaging Het
Pkd1l3 G A 8: 110,367,402 (GRCm39) V1210I probably damaging Het
Polr2a A T 11: 69,638,039 (GRCm39) H143Q possibly damaging Het
Potefam1 A T 2: 111,048,972 (GRCm39) M269K probably benign Het
Prdm12 G A 2: 31,544,186 (GRCm39) R263H probably damaging Het
Prkdc A C 16: 15,549,430 (GRCm39) K1998T probably damaging Het
Rab11fip1 A T 8: 27,643,051 (GRCm39) S583T probably damaging Het
Rnf157 T A 11: 116,237,921 (GRCm39) T567S probably benign Het
Rp1 T C 1: 4,417,917 (GRCm39) K1065R probably damaging Het
Rp1 A G 1: 4,418,760 (GRCm39) I784T probably benign Het
Rps10 A C 17: 27,850,182 (GRCm39) F150V probably benign Het
Rrp12 A T 19: 41,870,639 (GRCm39) F499I probably damaging Het
Sez6l2 G A 7: 126,562,535 (GRCm39) R604H probably damaging Het
Slc25a21 G T 12: 56,904,864 (GRCm39) Q57K probably benign Het
Slc27a2 A G 2: 126,395,234 (GRCm39) T54A possibly damaging Het
Slc9a9 T A 9: 95,111,011 (GRCm39) S610T probably benign Het
Smc1b A T 15: 84,970,335 (GRCm39) S973T probably benign Het
Smc6 G A 12: 11,329,734 (GRCm39) S164N possibly damaging Het
Sp1 A G 15: 102,316,314 (GRCm39) T32A possibly damaging Het
Spen T C 4: 141,202,946 (GRCm39) I1894V probably benign Het
Spen T C 4: 141,203,011 (GRCm39) K1872R possibly damaging Het
Stab1 C A 14: 30,873,541 (GRCm39) probably benign Het
Taar7d T G 10: 23,904,102 (GRCm39) F328C probably damaging Het
Ticam1 A T 17: 56,578,113 (GRCm39) S327R probably benign Het
Tmem248 C T 5: 130,258,295 (GRCm39) probably benign Het
Tom1 T C 8: 75,781,259 (GRCm39) S83P probably damaging Het
Txk T A 5: 72,856,453 (GRCm39) Y446F probably damaging Het
Ubap1l T A 9: 65,279,237 (GRCm39) C179S probably benign Het
Utrn T C 10: 12,331,185 (GRCm39) E474G possibly damaging Het
Vmn2r14 T C 5: 109,363,862 (GRCm39) M685V probably benign Het
Vmn2r7 A T 3: 64,623,881 (GRCm39) Y146* probably null Het
Wdr1 G A 5: 38,697,905 (GRCm39) T220M probably damaging Het
Xpo7 T C 14: 70,915,582 (GRCm39) D726G probably damaging Het
Zbtb14 C G 17: 69,694,759 (GRCm39) I152M probably benign Het
Zbtb3 A G 19: 8,780,771 (GRCm39) D128G probably damaging Het
Zeb1os1 A G 18: 5,583,794 (GRCm39) noncoding transcript Het
Zfp462 T A 4: 55,007,667 (GRCm39) D35E probably damaging Het
Zfp467 A G 6: 48,415,621 (GRCm39) S344P possibly damaging Het
Zfpm1 A T 8: 123,034,285 (GRCm39) D73V possibly damaging Het
Other mutations in Epha4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01315:Epha4 APN 1 77,375,194 (GRCm39) missense probably benign 0.00
IGL01350:Epha4 APN 1 77,483,492 (GRCm39) missense probably damaging 1.00
IGL01657:Epha4 APN 1 77,403,475 (GRCm39) missense probably damaging 1.00
IGL01872:Epha4 APN 1 77,359,676 (GRCm39) missense probably benign 0.03
IGL02366:Epha4 APN 1 77,403,348 (GRCm39) nonsense probably null
IGL02426:Epha4 APN 1 77,421,514 (GRCm39) missense probably benign 0.01
IGL02428:Epha4 APN 1 77,483,385 (GRCm39) missense possibly damaging 0.94
IGL02706:Epha4 APN 1 77,403,482 (GRCm39) missense probably damaging 1.00
IGL02716:Epha4 APN 1 77,357,602 (GRCm39) missense probably damaging 1.00
IGL03348:Epha4 APN 1 77,483,809 (GRCm39) missense possibly damaging 0.82
frog UTSW 1 77,481,076 (GRCm38) intron probably benign
R0324:Epha4 UTSW 1 77,360,188 (GRCm39) missense probably damaging 1.00
R0392:Epha4 UTSW 1 77,483,610 (GRCm39) missense probably benign 0.00
R0538:Epha4 UTSW 1 77,365,178 (GRCm39) missense probably damaging 1.00
R0562:Epha4 UTSW 1 77,365,124 (GRCm39) missense probably benign 0.00
R0885:Epha4 UTSW 1 77,359,576 (GRCm39) missense probably damaging 0.99
R1620:Epha4 UTSW 1 77,351,563 (GRCm39) missense probably benign 0.31
R1624:Epha4 UTSW 1 77,376,329 (GRCm39) missense probably damaging 1.00
R1654:Epha4 UTSW 1 77,351,405 (GRCm39) splice site probably null
R1755:Epha4 UTSW 1 77,364,460 (GRCm39) missense probably damaging 1.00
R1807:Epha4 UTSW 1 77,351,541 (GRCm39) missense probably benign 0.05
R2046:Epha4 UTSW 1 77,483,799 (GRCm39) missense probably damaging 1.00
R2504:Epha4 UTSW 1 77,359,628 (GRCm39) missense probably damaging 1.00
R2509:Epha4 UTSW 1 77,488,339 (GRCm39) missense possibly damaging 0.84
R2511:Epha4 UTSW 1 77,488,339 (GRCm39) missense possibly damaging 0.84
R3441:Epha4 UTSW 1 77,403,333 (GRCm39) missense possibly damaging 0.90
R3724:Epha4 UTSW 1 77,403,180 (GRCm39) splice site probably benign
R3901:Epha4 UTSW 1 77,357,539 (GRCm39) missense probably damaging 1.00
R3950:Epha4 UTSW 1 77,376,353 (GRCm39) missense probably damaging 1.00
R3951:Epha4 UTSW 1 77,376,353 (GRCm39) missense probably damaging 1.00
R3952:Epha4 UTSW 1 77,376,353 (GRCm39) missense probably damaging 1.00
R4012:Epha4 UTSW 1 77,366,731 (GRCm39) splice site probably benign
R4321:Epha4 UTSW 1 77,483,850 (GRCm39) critical splice acceptor site probably null
R4422:Epha4 UTSW 1 77,488,354 (GRCm39) missense probably damaging 0.99
R4898:Epha4 UTSW 1 77,366,712 (GRCm39) nonsense probably null
R5072:Epha4 UTSW 1 77,421,639 (GRCm39) missense probably damaging 1.00
R5270:Epha4 UTSW 1 77,483,244 (GRCm39) missense probably damaging 1.00
R5281:Epha4 UTSW 1 77,351,504 (GRCm39) missense probably benign
R5315:Epha4 UTSW 1 77,365,109 (GRCm39) critical splice donor site probably null
R5531:Epha4 UTSW 1 77,351,513 (GRCm39) missense probably benign
R5621:Epha4 UTSW 1 77,491,686 (GRCm39) utr 5 prime probably benign
R5648:Epha4 UTSW 1 77,375,162 (GRCm39) missense probably benign 0.25
R5747:Epha4 UTSW 1 77,483,520 (GRCm39) missense probably damaging 0.99
R5829:Epha4 UTSW 1 77,421,631 (GRCm39) missense probably benign 0.01
R6185:Epha4 UTSW 1 77,483,743 (GRCm39) missense probably damaging 1.00
R6486:Epha4 UTSW 1 77,360,186 (GRCm39) missense probably damaging 1.00
R6821:Epha4 UTSW 1 77,359,582 (GRCm39) missense possibly damaging 0.88
R6978:Epha4 UTSW 1 77,354,220 (GRCm39) missense probably damaging 1.00
R7039:Epha4 UTSW 1 77,483,422 (GRCm39) missense probably damaging 1.00
R7216:Epha4 UTSW 1 77,421,621 (GRCm39) missense probably damaging 1.00
R7270:Epha4 UTSW 1 77,376,422 (GRCm39) missense probably damaging 1.00
R7444:Epha4 UTSW 1 77,364,553 (GRCm39) missense probably damaging 1.00
R7737:Epha4 UTSW 1 77,357,649 (GRCm39) missense probably damaging 1.00
R7763:Epha4 UTSW 1 77,366,668 (GRCm39) critical splice donor site probably null
R7950:Epha4 UTSW 1 77,483,833 (GRCm39) missense probably damaging 0.99
R8297:Epha4 UTSW 1 77,483,547 (GRCm39) missense probably damaging 1.00
R8373:Epha4 UTSW 1 77,483,716 (GRCm39) missense possibly damaging 0.60
R8429:Epha4 UTSW 1 77,366,673 (GRCm39) missense probably benign 0.08
R8907:Epha4 UTSW 1 77,483,422 (GRCm39) missense probably damaging 1.00
R9024:Epha4 UTSW 1 77,365,169 (GRCm39) missense possibly damaging 0.79
Z1088:Epha4 UTSW 1 77,483,299 (GRCm39) missense possibly damaging 0.61
Z1176:Epha4 UTSW 1 77,359,648 (GRCm39) missense probably damaging 1.00
Z1176:Epha4 UTSW 1 77,350,370 (GRCm39) makesense probably null
Predicted Primers PCR Primer
(F):5'- ACTTCTTCCCCTACACGAAACATTGG -3'
(R):5'- AGCTACCTCAGGAATGCTGTCCTC -3'

Sequencing Primer
(F):5'- GGTCTTGAAACCAAGTCACTG -3'
(R):5'- TCTATCAAGTAGTCCCAGCATTCAG -3'
Posted On 2014-04-13