Mutagenetix > Incidental Mutation

Incidental Mutation 'R5270:Epha4'

400146

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

042835-MU

Accession Numbers

Genbank: NM_007936; MGI: 98277

Essential gene?

Probably essential (E-score: 0.957) question?

Stock #

R5270 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

77367185-77515088 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 77506607 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 255 (V255A)

Ref Sequence

ENSEMBL: ENSMUSP00000139640 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027451] [ENSMUST00000186930] [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: V255A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000027451
Gene: ENSMUSG00000026235
AA Change: V255A

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: ENSMUST00000186930

SMART Domains

Protein: ENSMUSP00000140370
Gene: ENSMUSG00000026235

Domain	Start	End	E-Value	Type
signal peptide	1	19	N/A	INTRINSIC
FN3	33	124	9.6e-11	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000188797
AA Change: V255A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000140954
Gene: ENSMUSG00000026235
AA Change: V255A

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 damaging
Transcript: ENSMUST00000188952
AA Change: V255A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000139640
Gene: ENSMUSG00000026235
AA Change: V255A

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

noncoding transcript
Transcript: ENSMUST00000189934

Predicted Effect

probably benign
Transcript: ENSMUST00000190149

Meta Mutation Damage Score

0.4589

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.6%

Validation Efficiency

98% (59/60)

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: 50 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsl5	T	C	19: 55,294,218	V585A	possibly damaging	Het
Adam6a	A	T	12: 113,544,127	H40L	possibly damaging	Het
Adamts20	G	A	15: 94,282,519	P1752S	probably benign	Het
Atpif1	A	G	4: 132,533,300	F27L	probably damaging	Het
B230104I21Rik	A	G	4: 154,349,593		probably benign	Het
C77080	T	C	4: 129,224,212	T208A	possibly damaging	Het
Ciz1	C	A	2: 32,374,499		probably null	Het
Crb1	T	A	1: 139,236,864	Y1174F	probably damaging	Het
Csf2rb2	A	T	15: 78,291,982		probably null	Het
Cyp3a25	A	T	5: 145,981,502	M433K	probably benign	Het
D1Ertd622e	T	C	1: 97,645,995	Q115R	probably damaging	Het
Dock4	A	G	12: 40,733,271	I735V	probably benign	Het
Dpp6	C	T	5: 27,634,534	S349L	probably damaging	Het
Epg5	T	A	18: 77,983,563	N1256K	possibly damaging	Het
Gabrb1	A	T	5: 72,108,326	D155V	probably damaging	Het
Gm13103	A	G	4: 143,851,898	M243V	probably damaging	Het
Gpr35	A	T	1: 92,982,577	T4S	probably benign	Het
Hcrt	T	C	11: 100,761,997	T64A	probably damaging	Het
Henmt1	G	A	3: 108,960,214	R355H	probably benign	Het
Hrh1	C	A	6: 114,481,218	R487S	possibly damaging	Het
Ints2	T	C	11: 86,215,795	S930G	probably damaging	Het
Irs2	G	A	8: 11,006,678	Q585*	probably null	Het
Kcns1	C	A	2: 164,168,329	R170L	probably benign	Het
Kdm3b	T	C	18: 34,827,414	S1351P	probably damaging	Het
Ly9	T	C	1: 171,601,162	T297A	probably damaging	Het
M6pr	G	A	6: 122,315,089	D127N	possibly damaging	Het
Nit2	G	A	16: 57,157,131	P179S	probably damaging	Het
Per1	T	C	11: 69,103,598	M516T	probably benign	Het
Pkdrej	A	T	15: 85,818,327	I1136N	probably damaging	Het
Prdm9	G	T	17: 15,553,363	T257K	probably benign	Het
Prkdc	T	C	16: 15,734,955	L2085P	probably damaging	Het
Rasgrf1	A	C	9: 90,026,694	E1240D	probably benign	Het
Rrh	T	C	3: 129,813,349	I142V	probably benign	Het
Saal1	G	T	7: 46,701,733		probably benign	Het
Sdcbp2	A	G	2: 151,584,892	I70V	probably benign	Het
Skida1	C	A	2: 18,047,649	A231S	probably benign	Het
Smtnl2	T	A	11: 72,399,917	T401S	probably benign	Het
Sntb1	C	G	15: 55,642,795	G461R	probably damaging	Het
Spag4	G	T	2: 156,065,933		probably benign	Het
Tbc1d9	A	G	8: 83,233,654	M179V	probably benign	Het
Tm9sf1	G	T	14: 55,636,481	T520N	probably damaging	Het
Tmem163	G	A	1: 127,491,552		probably benign	Het
Vmn1r47	A	T	6: 90,022,543	Q219L	probably damaging	Het
Vmn2r104	A	T	17: 20,038,266	C539S	probably damaging	Het
Wdr17	G	T	8: 54,643,186	S1024R	probably benign	Het
Zc3h4	A	G	7: 16,434,515	T850A	unknown	Het
Zfa-ps	A	G	10: 52,543,456		noncoding transcript	Het
Zfp146	G	T	7: 30,162,475	N47K	probably benign	Het
Zfp353-ps	G	T	8: 42,081,535		noncoding transcript	Het
Zfp607a	A	T	7: 27,878,305	K267*	probably null	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
R0562:Epha4	UTSW	1	77388487	missense	probably benign	0.00
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
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
R8907:Epha4	UTSW	1	77506785	missense	probably damaging	1.00
R9024:Epha4	UTSW	1	77388532	missense	possibly damaging	0.79
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'- AATGTCTTAGCCTTGCCACCTG -3'
(R):5'- CGTGTGTTCTACAAGAAGTGTCC -3'

Sequencing Primer
(F):5'- TTGCCACCTGGAGCTACAG -3'
(R):5'- GTGTTCTACAAGAAGTGTCCACTCAC -3'

Posted On

2016-07-06