Mutagenetix > Incidental Mutation

Incidental Mutation 'R2509:Epha4'

251669

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

040415-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.950) question?

Stock #

R2509 (G1)

Quality Score

203

Status

Validated

Chromosome

Chromosomal Location

77343822-77491725 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 77488339 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Valine at position 47 (A47V)

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

possibly damaging
Transcript: ENSMUST00000027451
AA Change: A47V

PolyPhen 2 Score 0.839 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000027451
Gene: ENSMUSG00000026235
AA Change: A47V

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

possibly damaging
Transcript: ENSMUST00000188797
AA Change: A47V

PolyPhen 2 Score 0.839 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000140954
Gene: ENSMUSG00000026235
AA Change: A47V

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

possibly damaging
Transcript: ENSMUST00000188952
AA Change: A47V

PolyPhen 2 Score 0.839 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000139640
Gene: ENSMUSG00000026235
AA Change: A47V

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: ENSMUST00000189147

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000189934

Predicted Effect

probably benign
Transcript: ENSMUST00000190149

Meta Mutation Damage Score

0.1457

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.4%

Validation Efficiency

96% (105/109)

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: 108 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	T	C	3: 124,200,102 (GRCm39)	I497V	probably benign	Het
4930571K23Rik	C	A	7: 124,968,311 (GRCm39)		noncoding transcript	Het
Abca17	G	T	17: 24,508,587 (GRCm39)		probably benign	Het
Ablim1	C	T	19: 57,140,791 (GRCm39)	R196Q	probably damaging	Het
Acot11	T	C	4: 106,612,516 (GRCm39)	I379V	possibly damaging	Het
Acot4	G	A	12: 84,088,647 (GRCm39)	G165D	probably damaging	Het
Agrn	A	T	4: 156,250,881 (GRCm39)		probably null	Het
Ahctf1	T	C	1: 179,598,258 (GRCm39)	S945G	possibly damaging	Het
Akr1c13	C	T	13: 4,248,583 (GRCm39)	R263C	probably damaging	Het
Arfgap1	T	A	2: 180,615,846 (GRCm39)		probably benign	Het
Arhgef3	A	G	14: 27,101,633 (GRCm39)	K103R	probably damaging	Het
Cabp1	A	T	5: 115,310,843 (GRCm39)	N211K	probably damaging	Het
Cacna1c	T	A	6: 118,711,943 (GRCm39)	D261V	probably damaging	Het
Car11	G	A	7: 45,350,783 (GRCm39)	G93E	probably damaging	Het
Card10	A	G	15: 78,664,473 (GRCm39)	I821T	probably benign	Het
Cast	T	C	13: 74,885,735 (GRCm39)	I277V	probably benign	Het
Cenpj	T	C	14: 56,769,694 (GRCm39)	K1165R	probably null	Het
Cenpk	A	G	13: 104,370,675 (GRCm39)		probably null	Het
Cfap251	A	G	5: 123,394,169 (GRCm39)	K353E	probably benign	Het
Cmya5	T	C	13: 93,230,066 (GRCm39)	Q1674R	probably benign	Het
Cnnm1	T	A	19: 43,430,325 (GRCm39)	V481D	probably damaging	Het
Cracdl	T	C	1: 37,664,381 (GRCm39)	M506V	probably benign	Het
Csmd3	CCTTTGCGCTT	CCTT	15: 47,604,632 (GRCm39)		probably null	Het
Cyp2c50	G	A	19: 40,079,013 (GRCm39)	V119I	probably benign	Het
Dnah7b	A	G	1: 46,234,447 (GRCm39)	T1460A	probably damaging	Het
Dnah8	G	A	17: 30,994,019 (GRCm39)	D3379N	probably benign	Het
Dnajc4	C	T	19: 6,968,111 (GRCm39)	R55H	probably damaging	Het
Ebf4	C	T	2: 130,148,482 (GRCm39)	R98*	probably null	Het
Ercc8	T	C	13: 108,320,251 (GRCm39)		probably benign	Het
Exo1	T	C	1: 175,733,399 (GRCm39)	F75S	probably damaging	Het
Fam168a	G	T	7: 100,483,391 (GRCm39)		probably null	Het
Fat3	G	A	9: 15,836,310 (GRCm39)	R4065W	possibly damaging	Het
Gm5431	T	A	11: 48,779,536 (GRCm39)	N740I	probably benign	Het
Gm5900	T	A	7: 104,599,571 (GRCm39)		noncoding transcript	Het
Gpi1	A	G	7: 33,905,348 (GRCm39)	S359P	probably damaging	Het
Gpr156	A	G	16: 37,768,149 (GRCm39)	R22G	probably benign	Het
Greb1	A	G	12: 16,774,923 (GRCm39)	V158A	probably damaging	Het
Grin2c	T	A	11: 115,141,894 (GRCm39)	K842*	probably null	Het
Gsta5	T	A	9: 78,202,089 (GRCm39)	M1K	probably null	Het
Hnf4a	T	A	2: 163,408,161 (GRCm39)	L329Q	probably damaging	Het
Hsp90ab1	A	G	17: 45,880,267 (GRCm39)	L92P	probably damaging	Het
Ido1	T	A	8: 25,074,501 (GRCm39)	R290*	probably null	Het
Ifnlr1	G	T	4: 135,432,559 (GRCm39)	D332Y	probably damaging	Het
Ift172	T	C	5: 31,420,312 (GRCm39)	N1108S	probably benign	Het
Igkv3-9	T	A	6: 70,565,728 (GRCm39)	M109K	probably benign	Het
Igsf10	T	C	3: 59,239,287 (GRCm39)	D298G	probably damaging	Het
Iqck	T	G	7: 118,475,505 (GRCm39)	M98R	probably benign	Het
Klk1b1	T	C	7: 43,618,803 (GRCm39)	V60A	probably damaging	Het
Krtap1-3	C	T	11: 99,481,653 (GRCm39)	E165K	unknown	Het
Lair1	A	G	7: 4,013,782 (GRCm39)	L155P	probably damaging	Het
Maco1	A	G	4: 134,531,699 (GRCm39)	S657P	probably damaging	Het
Mast4	G	T	13: 102,990,350 (GRCm39)	S57Y	probably damaging	Het
Mical3	T	C	6: 121,011,118 (GRCm39)	H360R	probably damaging	Het
Muc5b	A	T	7: 141,412,798 (GRCm39)	N1915Y	unknown	Het
Myh1	A	G	11: 67,096,423 (GRCm39)	I301V	probably benign	Het
Nck2	T	A	1: 43,593,393 (GRCm39)	V200E	probably damaging	Het
Odad4	T	G	11: 100,444,361 (GRCm39)	L222R	probably damaging	Het
Or2y1b	T	G	11: 49,209,048 (GRCm39)	L225R	probably damaging	Het
Or4b12	T	C	2: 90,096,030 (GRCm39)	Y248C	possibly damaging	Het
Or4c109	T	G	2: 88,817,775 (GRCm39)	Y257S	probably damaging	Het
Or4f60	T	A	2: 111,902,837 (GRCm39)	L30F	probably benign	Het
Or4k38	C	T	2: 111,166,076 (GRCm39)	V116I	probably damaging	Het
Or52n2c	G	A	7: 104,574,894 (GRCm39)	H26Y	probably benign	Het
Or5b101	T	A	19: 13,005,058 (GRCm39)	I212F	probably damaging	Het
Or8b12i	A	G	9: 20,082,525 (GRCm39)	L114P	probably damaging	Het
Otoa	C	T	7: 120,759,695 (GRCm39)	T1099I	probably benign	Het
Pask	T	A	1: 93,258,485 (GRCm39)	I288F	possibly damaging	Het
Pcnx4	T	C	12: 72,613,746 (GRCm39)	W564R	probably damaging	Het
Pip4p1	A	T	14: 51,167,115 (GRCm39)	Y129*	probably null	Het
Pitpnm2	T	C	5: 124,274,389 (GRCm39)	E240G	probably damaging	Het
Ppp1r16b	A	G	2: 158,603,383 (GRCm39)	Y436C	possibly damaging	Het
Pramel27	G	A	4: 143,578,561 (GRCm39)	V274I	probably benign	Het
Prkca	T	C	11: 107,870,032 (GRCm39)	Y37C	probably damaging	Het
Rad18	T	G	6: 112,652,883 (GRCm39)	H238P	possibly damaging	Het
Rap1b	T	A	10: 117,654,444 (GRCm39)	Q1L	probably damaging	Het
Rgs9	T	C	11: 109,159,798 (GRCm39)	Y178C	probably benign	Het
Rpl3l	A	T	17: 24,951,360 (GRCm39)	D87V	possibly damaging	Het
Scrn2	T	C	11: 96,923,992 (GRCm39)	V292A	possibly damaging	Het
Sdad1	A	G	5: 92,453,684 (GRCm39)	Y35H	probably benign	Het
Sez6l2	T	C	7: 126,552,944 (GRCm39)	S177P	probably benign	Het
Sh3bp1	C	T	15: 78,795,706 (GRCm39)	P612S	probably damaging	Het
Shank1	T	C	7: 44,001,148 (GRCm39)	S956P	unknown	Het
Shank1	G	A	7: 44,001,547 (GRCm39)	A1089T	unknown	Het
Shprh	G	A	10: 11,042,468 (GRCm39)	C817Y	probably damaging	Het
Spata22	C	T	11: 73,236,593 (GRCm39)	P300S	probably damaging	Het
Sstr2	A	T	11: 113,515,749 (GRCm39)	I223F	probably damaging	Het
Stom	C	T	2: 35,210,354 (GRCm39)	A217T	probably damaging	Het
Stpg1	T	C	4: 135,263,960 (GRCm39)	V341A	probably benign	Het
Tagap	A	G	17: 8,147,586 (GRCm39)	T99A	probably benign	Het
Tas1r2	A	G	4: 139,387,162 (GRCm39)	N207S	probably damaging	Het
Thbs2	A	G	17: 14,906,105 (GRCm39)	V265A	probably benign	Het
Thyn1	A	G	9: 26,911,316 (GRCm39)	R3G	possibly damaging	Het
Tia1	T	A	6: 86,401,312 (GRCm39)		probably null	Het
Tktl2	A	G	8: 66,965,504 (GRCm39)	E354G	probably benign	Het
Tmc8	A	G	11: 117,683,511 (GRCm39)	T689A	possibly damaging	Het
Tmem11	A	T	11: 60,755,807 (GRCm39)		probably null	Het
Tnik	T	C	3: 28,722,064 (GRCm39)	V1310A	probably damaging	Het
Trappc10	A	G	10: 78,047,357 (GRCm39)	S380P	possibly damaging	Het
Trim8	C	T	19: 46,503,734 (GRCm39)	P429S	probably benign	Het
Ttn	C	A	2: 76,687,756 (GRCm39)		probably benign	Het
Ulk2	T	C	11: 61,678,340 (GRCm39)	Y793C	probably benign	Het
Vill	G	A	9: 118,899,370 (GRCm39)	V337M	possibly damaging	Het
Vps53	C	A	11: 75,957,661 (GRCm39)	V364F	possibly damaging	Het
Zan	A	T	5: 137,454,848 (GRCm39)	I1396N	unknown	Het
Zfa-ps	A	C	10: 52,420,339 (GRCm39)		noncoding transcript	Het
Zfp426	T	C	9: 20,381,977 (GRCm39)	T337A	possibly damaging	Het
Zfp536	T	C	7: 37,267,403 (GRCm39)	E671G	possibly damaging	Het
Zfp985	A	G	4: 147,667,443 (GRCm39)	T104A	possibly damaging	Het

Other mutations in Epha4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R1509:Epha4	UTSW	1	77,357,523 (GRCm39)	missense	probably damaging	1.00
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
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'- TTCCATGACAGAACTCTCCAAAGG -3'
(R):5'- CATAAGTGGGCCCGAGTTTC -3'

Sequencing Primer
(F):5'- TCCAAAGGGAGTATTAGATTTCTCC -3'
(R):5'- TTTGATCAGATTGGCTATTCGCAC -3'

Posted On

2014-12-04