Mutagenetix > Incidental Mutations

Incidental Mutation 'R0562:Epha4'

45913

Institutional Source

Beutler Lab

Gene Symbol

Epha4

Ensembl Gene

ENSMUSG00000026235

Gene Name

Eph receptor A4

Synonyms

rb, Sek, Sek1, 2900005C20Rik, Cek8, Hek8, Tyro1

MMRRC Submission

038753-MU

Accession Numbers

Genbank: NM_007936; MGI: 98277

Is this an essential gene?

Probably essential (E-score: 0.895) question?

Stock #

R0562 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

77367185-77515088 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 77388487 bp

Zygosity

Heterozygous

Amino Acid Change

Lysine to Arginine at position 625 (K625R)

Ref Sequence

ENSEMBL: ENSMUSP00000139640 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027451] [ENSMUST00000188797] [ENSMUST00000188952] [ENSMUST00000190149]

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 benign
Transcript: ENSMUST00000027451
AA Change: K625R

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000027451
Gene: ENSMUSG00000026235
AA Change: K625R

Domain	Start	End	E-Value	Type
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: ENSMUST00000188797
AA Change: K625R

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000140954
Gene: ENSMUSG00000026235
AA Change: K625R

Domain	Start	End	E-Value	Type
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: ENSMUST00000188952
AA Change: K625R

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000139640
Gene: ENSMUSG00000026235
AA Change: K625R

Domain	Start	End	E-Value	Type
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

0.0585

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.9%

Validation Efficiency

100% (77/77)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
6430531B16Rik	T	C	7: 139,977,113	M120V	probably benign	Het
9530053A07Rik	G	A	7: 28,162,690	V2394I	probably benign	Het
Acadsb	C	T	7: 131,425,789	Q63*	probably null	Het
Adam26b	A	T	8: 43,520,371	N531K	probably benign	Het
Agt	A	G	8: 124,559,275	I356T	probably benign	Het
Ankmy1	A	T	1: 92,899,691		probably benign	Het
Anxa3	C	T	5: 96,812,884	S49L	possibly damaging	Het
Arap3	C	A	18: 37,975,540	R1279L	probably damaging	Het
Azin1	A	G	15: 38,493,581	I266T	probably benign	Het
Btnl7-ps	T	C	17: 34,533,524		noncoding transcript	Het
Car5a	T	A	8: 121,944,730	T22S	probably benign	Het
Card6	A	G	15: 5,105,166	I185T	probably damaging	Het
Ccdc81	T	C	7: 89,903,229	D11G	probably benign	Het
Cep170b	T	C	12: 112,739,189	V1127A	probably benign	Het
Ces1h	T	C	8: 93,357,143	I390M	unknown	Het
Col9a1	T	A	1: 24,179,279		probably null	Het
Cwc27	C	A	13: 104,661,357	E365*	probably null	Het
Cyb561a3	T	C	19: 10,586,710	V138A	probably benign	Het
Dcaf1	T	C	9: 106,844,122		probably benign	Het
Dnah17	A	G	11: 118,072,900	Y2516H	probably damaging	Het
Dsc2	T	A	18: 20,041,537	N521Y	probably damaging	Het
Dst	G	A	1: 34,227,981	E4835K	probably damaging	Het
Duox2	T	C	2: 122,289,599	E810G	probably damaging	Het
Dusp15	T	C	2: 152,951,348	N3S	possibly damaging	Het
Gata5	C	T	2: 180,327,759		probably null	Het
Gm10264	A	G	12: 88,329,666	D138G	unknown	Het
Gm14139	T	A	2: 150,192,574	C303S	probably damaging	Het
Grm5	A	G	7: 87,603,019	N159S	probably damaging	Het
Hivep3	T	A	4: 120,096,554	M689K	probably benign	Het
Ilvbl	G	T	10: 78,583,487	G499C	probably damaging	Het
Inpp4b	T	C	8: 81,768,151	I65T	possibly damaging	Het
Jarid2	T	C	13: 44,902,359	V208A	probably damaging	Het
Kcnh4	T	C	11: 100,750,244	M460V	possibly damaging	Het
Klhl22	A	G	16: 17,792,624	N580D	probably benign	Het
Klk15	T	A	7: 43,938,845	C192*	probably null	Het
Klk9	A	G	7: 43,795,666	E194G	probably damaging	Het
Lama1	G	T	17: 67,815,959	G2779V	probably damaging	Het
Lmln	C	T	16: 33,117,085	R607*	probably null	Het
Maea	T	C	5: 33,372,301	V377A	probably benign	Het
Matk	A	T	10: 81,259,691	Y115F	probably benign	Het
Mettl18	A	G	1: 163,996,493	K128E	probably benign	Het
Mrps22	T	C	9: 98,592,693	H246R	probably benign	Het
Msln	A	T	17: 25,753,006	M79K	probably benign	Het
Myf6	G	A	10: 107,494,559	P49L	probably benign	Het
Nat1	C	T	8: 67,491,311	T113I	possibly damaging	Het
Ncor2	C	T	5: 125,085,029	V394M	unknown	Het
Oas1c	T	C	5: 120,805,604		probably benign	Het
Olfr1053	T	A	2: 86,314,525	T254S	probably benign	Het
Otp	A	T	13: 94,877,409	T112S	probably damaging	Het
Pcdh7	A	G	5: 57,720,063	N320S	probably damaging	Het
Pdzd2	G	T	15: 12,592,278	F93L	probably damaging	Het
Phf20l1	A	G	15: 66,609,604	E283G	probably damaging	Het
Polr1e	T	C	4: 45,029,421	F342S	probably damaging	Het
Pp2d1	T	A	17: 53,539,168		probably benign	Het
Ptpn13	T	A	5: 103,516,425		probably null	Het
Reg3g	A	T	6: 78,467,488	H107Q	possibly damaging	Het
Rgl1	T	C	1: 152,539,945	K408E	probably damaging	Het
Samd4	T	C	14: 47,077,509	C309R	probably damaging	Het
Sestd1	C	A	2: 77,230,722	W104L	probably benign	Het
Sfmbt1	T	A	14: 30,811,373		probably null	Het
Slc22a21	T	A	11: 53,979,620	K80*	probably null	Het
Snx20	T	A	8: 88,630,002	Q62L	probably benign	Het
Stk40	C	A	4: 126,138,801		probably benign	Het
Taf2	A	T	15: 55,022,188		probably benign	Het
Tcf23	C	T	5: 30,970,310	P152L	probably damaging	Het
Tex29	T	C	8: 11,844,138		probably benign	Het
Tjp3	A	G	10: 81,280,555	V235A	probably damaging	Het
Tns3	A	T	11: 8,493,262	I367N	possibly damaging	Het
Ttc26	T	A	6: 38,401,129	V292E	probably damaging	Het
Ttn	T	A	2: 76,712,911	M33244L	probably benign	Het
Ush2a	A	T	1: 188,356,847	N333I	probably damaging	Het
Usp34	T	C	11: 23,432,406		probably benign	Het
Vmn1r204	A	C	13: 22,556,678	S160R	probably benign	Het
Vmn2r75	C	T	7: 86,148,241	W788*	probably null	Het
Vwa5b1	T	C	4: 138,635,711		probably benign	Het
Zbtb7a	A	G	10: 81,148,329	E535G	probably benign	Het
Zranb3	T	C	1: 128,036,558	D144G	probably benign	Het

Other mutations in Epha4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01315:Epha4	APN	1	77398557	missense	probably benign	0.00
IGL01350:Epha4	APN	1	77506855	missense	probably damaging	1.00
IGL01657:Epha4	APN	1	77426838	missense	probably damaging	1.00
IGL01872:Epha4	APN	1	77383039	missense	probably benign	0.03
IGL02366:Epha4	APN	1	77426711	nonsense	probably null
IGL02426:Epha4	APN	1	77444877	missense	probably benign	0.01
IGL02428:Epha4	APN	1	77506748	missense	possibly damaging	0.94
IGL02706:Epha4	APN	1	77426845	missense	probably damaging	1.00
IGL02716:Epha4	APN	1	77380965	missense	probably damaging	1.00
IGL03348:Epha4	APN	1	77507172	missense	possibly damaging	0.82
frog	UTSW	1	77481076	intron	probably benign
R0324:Epha4	UTSW	1	77383551	missense	probably damaging	1.00
R0392:Epha4	UTSW	1	77506973	missense	probably benign	0.00
R0538:Epha4	UTSW	1	77388541	missense	probably damaging	1.00
R0885:Epha4	UTSW	1	77382939	missense	probably damaging	0.99
R1509:Epha4	UTSW	1	77380886	missense	probably damaging	1.00
R1620:Epha4	UTSW	1	77374926	missense	probably benign	0.31
R1624:Epha4	UTSW	1	77399692	missense	probably damaging	1.00
R1654:Epha4	UTSW	1	77374768	splice site	probably null
R1755:Epha4	UTSW	1	77387823	missense	probably damaging	1.00
R1807:Epha4	UTSW	1	77374904	missense	probably benign	0.05
R2046:Epha4	UTSW	1	77507162	missense	probably damaging	1.00
R2504:Epha4	UTSW	1	77382991	missense	probably damaging	1.00
R2509:Epha4	UTSW	1	77511702	missense	possibly damaging	0.84
R2511:Epha4	UTSW	1	77511702	missense	possibly damaging	0.84
R3441:Epha4	UTSW	1	77426696	missense	possibly damaging	0.90
R3724:Epha4	UTSW	1	77426543	splice site	probably benign
R3901:Epha4	UTSW	1	77380902	missense	probably damaging	1.00
R3950:Epha4	UTSW	1	77399716	missense	probably damaging	1.00
R3951:Epha4	UTSW	1	77399716	missense	probably damaging	1.00
R3952:Epha4	UTSW	1	77399716	missense	probably damaging	1.00
R4012:Epha4	UTSW	1	77390094	splice site	probably benign
R4321:Epha4	UTSW	1	77507213	critical splice acceptor site	probably null
R4422:Epha4	UTSW	1	77511717	missense	probably damaging	0.99
R4898:Epha4	UTSW	1	77390075	nonsense	probably null
R5072:Epha4	UTSW	1	77445002	missense	probably damaging	1.00
R5270:Epha4	UTSW	1	77506607	missense	probably damaging	1.00
R5281:Epha4	UTSW	1	77374867	missense	probably benign
R5315:Epha4	UTSW	1	77388472	critical splice donor site	probably null
R5531:Epha4	UTSW	1	77374876	missense	probably benign
R5621:Epha4	UTSW	1	77515049	utr 5 prime	probably benign
R5648:Epha4	UTSW	1	77398525	missense	probably benign	0.25
R5747:Epha4	UTSW	1	77506883	missense	probably damaging	0.99
R5829:Epha4	UTSW	1	77444994	missense	probably benign	0.01
R6185:Epha4	UTSW	1	77507106	missense	probably damaging	1.00
R6486:Epha4	UTSW	1	77383549	missense	probably damaging	1.00
R6821:Epha4	UTSW	1	77382945	missense	possibly damaging	0.88
R6978:Epha4	UTSW	1	77377583	missense	probably damaging	1.00
R7039:Epha4	UTSW	1	77506785	missense	probably damaging	1.00
R7216:Epha4	UTSW	1	77444984	missense	probably damaging	1.00
R7270:Epha4	UTSW	1	77399785	missense	probably damaging	1.00
R7444:Epha4	UTSW	1	77387916	missense	probably damaging	1.00
R7737:Epha4	UTSW	1	77381012	missense	probably damaging	1.00
R7763:Epha4	UTSW	1	77390031	critical splice donor site	probably null
R7950:Epha4	UTSW	1	77507196	missense	probably damaging	0.99
R8297:Epha4	UTSW	1	77506910	missense	probably damaging	1.00
R8373:Epha4	UTSW	1	77507079	missense	possibly damaging	0.60
R8429:Epha4	UTSW	1	77390036	missense	probably benign	0.08
Z1088:Epha4	UTSW	1	77506662	missense	possibly damaging	0.61
Z1176:Epha4	UTSW	1	77373733	makesense	probably null
Z1176:Epha4	UTSW	1	77383011	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GCACCAAAGTTCCTTACAGAACATTGC -3'
(R):5'- GTCAACGGCCATAGAGTTAACCCAG -3'

Sequencing Primer
(F):5'- GACGTACGTGCAATACACTC -3'
(R):5'- GCCATAGAGTTAACCCAGCTTTTG -3'

Posted On

2013-06-11