Mutagenetix > Incidental Mutation

Incidental Mutation 'R6151:Diaph1'

489310

Institutional Source

Beutler Lab

Gene Symbol

Diaph1

Ensembl Gene

ENSMUSG00000024456

Gene Name

diaphanous related formin 1

Synonyms

Drf1, Dia1, D18Wsu154e, mDia1, Diap1, p140mDia

MMRRC Submission

044298-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6151 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

37843601-37935476 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 37853353 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Alanine at position 1158 (E1158A)

Ref Sequence

ENSEMBL: ENSMUSP00000111297 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025337] [ENSMUST00000080033] [ENSMUST00000115629] [ENSMUST00000115631] [ENSMUST00000115634]

AlphaFold

O08808

PDB Structure

Crystal structure of the core FH2 domain of mouse mDia1 [X-RAY DIFFRACTION]
Crystal structure of mDIA1 GBD-FH3 in complex with RhoC-GMPPNP [X-RAY DIFFRACTION]
Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD) [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF THE DIMERIC REGULATORY DOMAIN OF MOUSE DIAPHANEOUS-RELATED FORMIN (DRF), MDIA1 [X-RAY DIFFRACTION]
Crystal structure of the autoinhibitory switch in Formin mDia1; the DID/DAD complex [X-RAY DIFFRACTION]
Mouse Profilin IIa in complex with a double repeat from the FH1 domain of mDia1 [X-RAY DIFFRACTION]
Crystal structure of MDIA1-TSH GBD-FH3 in complex with CDC42-GMPPNP [X-RAY DIFFRACTION]
Crystal structure of complex between amino and carboxy terminal fragments of mDia1 [X-RAY DIFFRACTION]
Autoinhibited Formin mDia1 Structure [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000025337
AA Change: E1167A

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000025337
Gene: ENSMUSG00000024456
AA Change: E1167A

Domain	Start	End	E-Value	Type
low complexity region	5	13	N/A	INTRINSIC
Drf_GBD	84	268	1.07e-57	SMART
Drf_FH3	274	466	2.06e-68	SMART
coiled coil region	471	571	N/A	INTRINSIC
Pfam:Drf_FH1	609	756	6.1e-43	PFAM
FH2	761	1206	2.46e-182	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000080033
AA Change: E1158A

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000078942
Gene: ENSMUSG00000024456
AA Change: E1158A

Domain	Start	End	E-Value	Type
low complexity region	5	13	N/A	INTRINSIC
Drf_GBD	75	259	1.07e-57	SMART
Drf_FH3	265	457	2.06e-68	SMART
coiled coil region	462	562	N/A	INTRINSIC
Pfam:Drf_FH1	589	747	7.9e-52	PFAM
FH2	752	1197	3.73e-182	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000115629
AA Change: E1123A

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000111292
Gene: ENSMUSG00000024456
AA Change: E1123A

Domain	Start	End	E-Value	Type
Drf_GBD	40	224	1.07e-57	SMART
Drf_FH3	230	422	2.06e-68	SMART
coiled coil region	427	527	N/A	INTRINSIC
Pfam:Drf_FH1	554	712	7.6e-52	PFAM
FH2	717	1162	3.73e-182	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000115631
AA Change: E1123A

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000111294
Gene: ENSMUSG00000024456
AA Change: E1123A

Domain	Start	End	E-Value	Type
Drf_GBD	40	224	1.07e-57	SMART
Drf_FH3	230	422	2.06e-68	SMART
coiled coil region	427	527	N/A	INTRINSIC
Pfam:Drf_FH1	554	712	1.1e-51	PFAM
FH2	717	1162	2.46e-182	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000115634
AA Change: E1158A

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000111297
Gene: ENSMUSG00000024456
AA Change: E1158A

Domain	Start	End	E-Value	Type
low complexity region	5	13	N/A	INTRINSIC
Drf_GBD	75	259	1.07e-57	SMART
Drf_FH3	265	457	2.06e-68	SMART
coiled coil region	462	562	N/A	INTRINSIC
Pfam:Drf_FH1	589	747	9.4e-52	PFAM
FH2	752	1197	2.46e-182	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124822

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127346

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183927

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.1%
20x: 94.4%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a member of the formin family of proteins that play important roles in cytoskeletal rearragnement by nucleation of actin filaments. Mice lacking the encoded protein develop age-dependent myeloproliferative defects resembling human myeloproliferative syndrome and myelodysplastic syndromes. Trafficking of T lymphocytes to secondary lymphoid organs and egression of thymocytes from the thymus are impaired in these animals. Lack of the encoded protein in T lymphocytes and thymocytes also reduces chemotaxis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2016]
PHENOTYPE: Mice homozygous for a null allele exhibit abnormal hematopoiesis, bone marrow cell morphology, spleen morphology, skin physiology, skull morphology, and postnatal growth. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410141K09Rik	A	T	13: 66,431,681	C248S	probably damaging	Het
3110009E18Rik	A	G	1: 120,171,486		probably null	Het
4930550C14Rik	G	T	9: 53,414,383	R73S	probably damaging	Het
Abca1	A	G	4: 53,085,261	V517A	probably benign	Het
Adck5	A	T	15: 76,594,687	K370N	possibly damaging	Het
Akap6	A	C	12: 53,025,792	D981A	probably damaging	Het
Apbb1	G	A	7: 105,574,252	R51*	probably null	Het
Arhgap23	A	G	11: 97,500,412	M1252V	probably benign	Het
Arhgef1	A	G	7: 24,917,942	T354A	probably benign	Het
Arid1a	G	T	4: 133,684,976	Q1636K	unknown	Het
Asmt	C	T	X: 170,676,467	A237V	possibly damaging	Het
Brat1	T	A	5: 140,705,961	C43S	probably benign	Het
Cd36	T	C	5: 17,795,595	Y370C	probably damaging	Het
Ceacam12	A	T	7: 18,069,105	L145F	probably benign	Het
Col24a1	C	T	3: 145,314,054	T62I	probably damaging	Het
Col6a3	G	T	1: 90,813,753	N652K	possibly damaging	Het
Dcbld1	T	C	10: 52,304,660	L140P	probably damaging	Het
Dhrs13	G	A	11: 78,036,982	C218Y	probably damaging	Het
Emp2	A	C	16: 10,292,281	F20C	probably damaging	Het
Enpep	T	C	3: 129,332,418	I22V	possibly damaging	Het
Epha2	A	G	4: 141,318,480		probably null	Het
Eprs	G	T	1: 185,407,754		probably null	Het
Etl4	T	A	2: 20,713,360	I304N	probably damaging	Het
Exoc3l2	C	A	7: 19,491,745	S89*	probably null	Het
F5	A	T	1: 164,181,635	I325F	probably damaging	Het
F5	G	A	1: 164,190,187	C611Y	probably damaging	Het
Fam133b	A	T	5: 3,559,133	S116C	probably null	Het
Fam13b	A	T	18: 34,494,277	D190E	probably damaging	Het
Fam169a	T	G	13: 97,093,630	Y58D	probably damaging	Het
Far1	G	A	7: 113,561,396	R383H	possibly damaging	Het
Fnbp1l	T	C	3: 122,570,930	K52R	possibly damaging	Het
Foxj3	C	A	4: 119,623,271	Q469K	unknown	Het
Frs3	A	T	17: 47,689,088		probably benign	Het
Gdpd3	A	G	7: 126,775,502	S290G	probably benign	Het
Gm6768	T	G	12: 119,261,106		noncoding transcript	Het
Gmip	T	A	8: 69,817,085	L610Q	probably damaging	Het
Gprc5c	T	A	11: 114,864,025	I176N	probably damaging	Het
Grm3	A	G	5: 9,511,556	F765L	probably damaging	Het
Hhat	A	T	1: 192,759,757	L2Q	probably damaging	Het
Hrasls5	C	T	19: 7,619,291	P148S	probably damaging	Het
Hspbap1	T	C	16: 35,817,222	S214P	probably damaging	Het
Ighv1-62-3	C	A	12: 115,461,289	V21F	probably damaging	Het
Kcnj15	A	T	16: 95,295,668	K50*	probably null	Het
Kidins220	T	C	12: 25,056,909	S1454P	possibly damaging	Het
Kl	T	A	5: 150,988,853	M689K	possibly damaging	Het
Klhl23	T	G	2: 69,824,854	L356R	probably damaging	Het
Kndc1	A	T	7: 139,921,213	D806V	probably benign	Het
Krt26	T	C	11: 99,337,489	E139G	probably benign	Het
Lefty1	T	C	1: 180,935,116	F3L	unknown	Het
Madd	A	C	2: 91,165,457	Y853*	probably null	Het
Map1a	T	A	2: 121,289,823	D63E	probably benign	Het
Mdn1	T	A	4: 32,684,735	V815E	probably damaging	Het
Mettl3	A	G	14: 52,295,020	Y569H	probably damaging	Het
Mknk2	T	C	10: 80,669,025		probably null	Het
Mpp3	C	A	11: 102,008,566	R376S	probably benign	Het
Nup160	T	A	2: 90,690,105	Y293*	probably null	Het
Nupl1	A	T	14: 60,244,616	F100I	possibly damaging	Het
Nxpe2	A	C	9: 48,326,191	L255V	probably benign	Het
Olfr1423	T	C	19: 12,036,736	E2G	probably benign	Het
Olfr167	A	T	16: 19,515,531	L35Q	probably damaging	Het
Olfr390	T	A	11: 73,787,695	Y252*	probably null	Het
Olfr479	A	G	7: 108,055,899	I306V	probably benign	Het
Padi3	A	T	4: 140,796,394	D248E	probably damaging	Het
Paxip1	G	T	5: 27,761,618	H637N	probably damaging	Het
Pde4b	T	A	4: 102,601,551	M296K	probably damaging	Het
Pkd1	A	G	17: 24,575,606	H2089R	probably benign	Het
Prpf40a	T	C	2: 53,157,915	M197V	probably benign	Het
Rhebl1	T	C	15: 98,878,279	I165V	probably benign	Het
Rock1	A	T	18: 10,106,426	V481E	possibly damaging	Het
Rtca	T	A	3: 116,507,827	T24S	probably benign	Het
Serpina3c	T	A	12: 104,152,068	I4F	possibly damaging	Het
Serpina3j	C	A	12: 104,317,390	A249E	possibly damaging	Het
Slc38a9	A	G	13: 112,689,376	N116S	probably damaging	Het
Slco2b1	C	T	7: 99,690,563	V58I	possibly damaging	Het
Slfn8	T	A	11: 83,017,321	Y132F	probably damaging	Het
Smg6	T	G	11: 75,156,207	I1242S	probably damaging	Het
Tap2	G	T	17: 34,212,047	V374L	probably benign	Het
Tbc1d10b	G	A	7: 127,207,996	T123M	probably damaging	Het
Tenm2	A	C	11: 36,008,783	V2516G	probably damaging	Het
Tenm3	C	T	8: 48,395,573	R12Q	probably damaging	Het
Tmem130	T	A	5: 144,737,851	M355L	probably benign	Het
Tns4	C	T	11: 99,075,550	S433N	probably benign	Het
Traip	G	T	9: 107,970,619		probably null	Het
Trmo	G	A	4: 46,389,390	R2C	probably damaging	Het
Ttn	A	T	2: 76,944,160	I2134N	probably damaging	Het
Uba1y	A	G	Y: 825,984	D380G	probably benign	Het
Ube2t	T	A	1: 134,967,960		probably null	Het
Ugdh	A	T	5: 65,417,581	Y367*	probably null	Het
Usp45	A	C	4: 21,810,797	D331A	probably damaging	Het
Vmn1r84	G	T	7: 12,361,914	T284K	possibly damaging	Het
Vmn1r91	T	A	7: 20,101,435	F93Y	probably benign	Het
Vmn2r77	T	A	7: 86,801,670	Y255N	probably benign	Het
Vmn2r96	A	T	17: 18,583,959	Q490H	probably benign	Het
Vwa2	A	G	19: 56,903,465		probably null	Het
Vwf	A	G	6: 125,657,065	K169E	unknown	Het
Zc3h7b	G	C	15: 81,778,710		probably null	Het
Zfp458	T	A	13: 67,257,598	H259L	possibly damaging	Het
Zfp647	G	A	15: 76,912,085	P125L	probably damaging	Het
Zfp804b	A	G	5: 6,769,910	V1051A	probably benign	Het

Other mutations in Diaph1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00518:Diaph1	APN	18	37893348	critical splice donor site	probably null
IGL01432:Diaph1	APN	18	37897504	missense	unknown
IGL01646:Diaph1	APN	18	37893416	critical splice acceptor site	probably null
IGL01676:Diaph1	APN	18	37856188	nonsense	probably null
IGL01731:Diaph1	APN	18	37853709	critical splice acceptor site	probably benign
IGL01921:Diaph1	APN	18	37856208	missense	possibly damaging	0.73
IGL02200:Diaph1	APN	18	37890682	missense	unknown
IGL02258:Diaph1	APN	18	37853330	missense	probably damaging	0.99
IGL02325:Diaph1	APN	18	37853600	missense	probably damaging	1.00
IGL03304:Diaph1	APN	18	37854573	missense	possibly damaging	0.47
albatross	UTSW	18	37853679	nonsense	probably null
cucamonga	UTSW	18	37896093	critical splice donor site	probably null
damselfly	UTSW	18	37897550	nonsense	probably null
devastator	UTSW	18	37896093	critical splice donor site	probably null
fishnets	UTSW	18	37895300	critical splice acceptor site	probably null
Guangzhou	UTSW	18	37896093	critical splice donor site	probably null
saran	UTSW	18	37855804	missense	probably damaging	1.00
seethrough	UTSW	18	37889769	missense	probably damaging	1.00
sheer	UTSW	18	37896093	critical splice donor site	probably benign
R0137:Diaph1	UTSW	18	37891849	missense	unknown
R0446:Diaph1	UTSW	18	37853590	missense	possibly damaging	0.94
R0523:Diaph1	UTSW	18	37856500	missense	possibly damaging	0.56
R1433:Diaph1	UTSW	18	37905134	missense	unknown
R1532:Diaph1	UTSW	18	37896093	critical splice donor site	probably null
R1534:Diaph1	UTSW	18	37896093	critical splice donor site	probably null
R1535:Diaph1	UTSW	18	37896093	critical splice donor site	probably null
R1536:Diaph1	UTSW	18	37896093	critical splice donor site	probably null
R1537:Diaph1	UTSW	18	37896093	critical splice donor site	probably null
R1611:Diaph1	UTSW	18	37900702	missense	unknown
R1756:Diaph1	UTSW	18	37854573	missense	possibly damaging	0.47
R1771:Diaph1	UTSW	18	37891018	missense	unknown
R1812:Diaph1	UTSW	18	37891018	missense	unknown
R2121:Diaph1	UTSW	18	37896389	missense	unknown
R3710:Diaph1	UTSW	18	37845484	missense	probably damaging	1.00
R3891:Diaph1	UTSW	18	37900638	splice site	probably benign
R3892:Diaph1	UTSW	18	37900638	splice site	probably benign
R4077:Diaph1	UTSW	18	37853583	missense	possibly damaging	0.68
R4079:Diaph1	UTSW	18	37853583	missense	possibly damaging	0.68
R4771:Diaph1	UTSW	18	37853551	missense	probably damaging	1.00
R4815:Diaph1	UTSW	18	37895203	missense	unknown
R5242:Diaph1	UTSW	18	37851635	missense	probably damaging	1.00
R5294:Diaph1	UTSW	18	37897550	nonsense	probably null
R5294:Diaph1	UTSW	18	37897580	missense	unknown
R5349:Diaph1	UTSW	18	37891072	missense	unknown
R5427:Diaph1	UTSW	18	37890595	missense	unknown
R5623:Diaph1	UTSW	18	37896093	critical splice donor site	probably benign
R5677:Diaph1	UTSW	18	37855951	missense	probably damaging	1.00
R5730:Diaph1	UTSW	18	37903776	missense	unknown
R5767:Diaph1	UTSW	18	37853355	missense	probably damaging	1.00
R5925:Diaph1	UTSW	18	37891935	missense	unknown
R6823:Diaph1	UTSW	18	37876383	splice site	probably null
R6876:Diaph1	UTSW	18	37896373	missense	unknown
R6925:Diaph1	UTSW	18	37853679	nonsense	probably null
R6983:Diaph1	UTSW	18	37889769	missense	probably damaging	1.00
R7073:Diaph1	UTSW	18	37889814	critical splice acceptor site	probably null
R7248:Diaph1	UTSW	18	37889776	missense	probably benign	0.26
R7400:Diaph1	UTSW	18	37854502	missense	probably damaging	1.00
R7497:Diaph1	UTSW	18	37895300	critical splice acceptor site	probably null
R7544:Diaph1	UTSW	18	37893269	splice site	probably null
R7703:Diaph1	UTSW	18	37890809	missense	unknown
R7834:Diaph1	UTSW	18	37853709	critical splice acceptor site	probably benign
R8073:Diaph1	UTSW	18	37891797	missense	unknown
R8378:Diaph1	UTSW	18	37891953	missense	unknown
R8847:Diaph1	UTSW	18	37854537	missense	possibly damaging	0.71
R8947:Diaph1	UTSW	18	37853701	missense	probably damaging	1.00
R8990:Diaph1	UTSW	18	37855804	missense	probably damaging	1.00
R9059:Diaph1	UTSW	18	37889745	missense	possibly damaging	0.53
R9189:Diaph1	UTSW	18	37891109	missense	unknown
R9297:Diaph1	UTSW	18	37889775	missense	probably benign	0.26
R9438:Diaph1	UTSW	18	37893390	missense	unknown
R9439:Diaph1	UTSW	18	37896359	critical splice donor site	probably null
R9538:Diaph1	UTSW	18	37853417	missense	probably damaging	1.00
R9596:Diaph1	UTSW	18	37891058	missense	unknown
R9752:Diaph1	UTSW	18	37903071	missense	unknown
R9762:Diaph1	UTSW	18	37854536	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AATCCAGCACCCAGAGTTTG -3'
(R):5'- AAGGAGCTAGGTGACTACTTCG -3'

Sequencing Primer
(F):5'- AGTTTGGAGGCAGAGGCTG -3'
(R):5'- CGTCTTTGACCCTAAGAAGTTG -3'

Posted On

2017-10-10