Mutagenetix > Incidental Mutations

Incidental Mutation 'R1756:Diaph1'

194910

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

039788-MU

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1756 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

37843601-37935476 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 37854573 bp

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 1043 (D1043E)

Ref Sequence

ENSEMBL: ENSMUSP00000111297 (fasta)

Gene Model

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

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 benign
Transcript: ENSMUST00000025337
AA Change: D1052E

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000025337
Gene: ENSMUSG00000024456
AA Change: D1052E

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 benign
Transcript: ENSMUST00000080033
AA Change: D1043E

PolyPhen 2 Score 0.058 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000078942
Gene: ENSMUSG00000024456
AA Change: D1043E

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 benign
Transcript: ENSMUST00000115629
AA Change: D1008E

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000111292
Gene: ENSMUSG00000024456
AA Change: D1008E

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 benign
Transcript: ENSMUST00000115631
AA Change: D1008E

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000111294
Gene: ENSMUSG00000024456
AA Change: D1008E

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

possibly damaging
Transcript: ENSMUST00000115634
AA Change: D1043E

PolyPhen 2 Score 0.474 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000111297
Gene: ENSMUSG00000024456
AA Change: D1043E

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

Meta Mutation Damage Score

0.0735

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.5%
20x: 93.0%

Validation Efficiency

100% (96/96)

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: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2010111I01Rik	T	A	13: 63,068,061	H382Q	possibly damaging	Het
A330008L17Rik	C	A	8: 99,421,882		noncoding transcript	Het
Acin1	A	G	14: 54,665,204	V377A	probably benign	Het
Adam39	A	T	8: 40,825,324	I251F	probably damaging	Het
Adnp2	A	T	18: 80,127,697	*1166K	probably null	Het
Akap12	T	A	10: 4,357,574	D1461E	probably benign	Het
Apba1	A	G	19: 23,893,692	D296G	possibly damaging	Het
Apol7a	G	T	15: 77,393,471	L26M	possibly damaging	Het
Bcl2	C	T	1: 106,712,392	M163I	probably damaging	Het
Cap2	T	G	13: 46,531,013	I53R	probably benign	Het
Ccdc105	T	A	10: 78,747,197	K451M	probably damaging	Het
Ccdc74a	T	C	16: 17,650,468	V318A	possibly damaging	Het
Ccnb2	A	G	9: 70,410,788	V234A	probably benign	Het
Cd207	C	T	6: 83,675,597	V184I	probably benign	Het
Cdk12	C	A	11: 98,241,761	C1005*	probably null	Het
Cep83	T	C	10: 94,750,267	S344P	probably damaging	Het
Ces1g	A	T	8: 93,306,954	Y447N	probably benign	Het
Cfap54	A	T	10: 93,048,061	L277Q	probably damaging	Het
Cfh	A	G	1: 140,100,877	Y1027H	probably damaging	Het
Clcnkb	T	A	4: 141,415,214	I28F	possibly damaging	Het
Clec4d	A	G	6: 123,267,109	D59G	probably damaging	Het
Colq	G	A	14: 31,547,452	P153S	probably damaging	Het
Crybg1	T	A	10: 43,986,279	T1500S	probably damaging	Het
Cyp2d34	T	A	15: 82,617,524	R262W	probably damaging	Het
Dennd4b	C	G	3: 90,271,605	L559V	probably damaging	Het
Dhrs1	A	G	14: 55,739,309	V306A	probably benign	Het
Dis3	G	T	14: 99,086,103	D538E	probably damaging	Het
Dnaic2	T	G	11: 114,750,380	S344A	probably benign	Het
Dner	C	T	1: 84,445,590	V431M	probably damaging	Het
Dnm1l	A	G	16: 16,342,695		probably null	Het
Eps15	T	G	4: 109,312,918	L139*	probably null	Het
Fam193a	T	A	5: 34,466,292	I55N	possibly damaging	Het
Gm10308	T	A	17: 91,088,957	Y102*	probably null	Het
Gm10509	A	G	17: 21,690,855	K30E	possibly damaging	Het
Gm4778	A	T	3: 94,266,218	M174L	probably benign	Het
Gm9573	A	T	17: 35,619,239		probably benign	Het
Gpr155	T	C	2: 73,367,577	M400V	probably benign	Het
H2-M10.2	T	C	17: 36,286,123		probably benign	Het
Heatr1	G	T	13: 12,396,460	A61S	probably benign	Het
Helb	G	T	10: 120,094,242	T744K	probably damaging	Het
Hmcn1	C	A	1: 150,599,030	W4702L	probably damaging	Het
Hmcn2	C	T	2: 31,396,120	R2095W	probably damaging	Het
Igfbp3	G	C	11: 7,208,461	D267E	probably damaging	Het
Ighmbp2	T	A	19: 3,268,669	H469L	probably damaging	Het
Kcnj3	A	C	2: 55,437,220	K7T	probably damaging	Het
Krtap5-5	T	G	7: 142,229,621	K97N	unknown	Het
Lcor	T	C	19: 41,559,266	S430P	probably benign	Het
Lpin1	A	G	12: 16,538,540	V883A	probably damaging	Het
Lrp1b	T	C	2: 41,110,825	Y2243C	probably damaging	Het
Lrrc46	G	A	11: 97,034,730		probably benign	Het
Man1c1	G	C	4: 134,703,438	P11R	probably damaging	Het
Mpdz	C	T	4: 81,306,877	V1438M	possibly damaging	Het
Ncbp1	T	A	4: 46,169,131	L635*	probably null	Het
Nipbl	T	C	15: 8,338,551	N1202D	possibly damaging	Het
Nphs1	A	G	7: 30,461,534	D196G	probably benign	Het
Nupl1	A	T	14: 60,244,670		probably benign	Het
Olfr1008	A	G	2: 85,690,083	Y218C	probably damaging	Het
Olfr1360	A	G	13: 21,674,695	I83T	probably benign	Het
Olfr901	A	T	9: 38,430,995	I238F	probably benign	Het
Pax8	A	T	2: 24,435,821	N350K	probably damaging	Het
Pik3cd	T	C	4: 149,658,750	K298E	probably benign	Het
Pkd1	C	T	17: 24,594,485	R4000C	probably damaging	Het
Pkn2	A	T	3: 142,810,727	V546D	possibly damaging	Het
Plcg2	A	G	8: 117,592,708	K673E	probably benign	Het
Pld4	T	G	12: 112,763,392		probably null	Het
Plek	A	T	11: 16,992,901	N130K	probably damaging	Het
Prune2	G	A	19: 17,123,704	D2191N	probably benign	Het
Ptgis	T	C	2: 167,206,803	Y431C	probably damaging	Het
Rhbdf2	T	C	11: 116,607,266	S36G	probably benign	Het
Rtn4ip1	C	T	10: 43,910,830	A178V	probably damaging	Het
Rxfp1	A	G	3: 79,670,881	S168P	probably benign	Het
Sec24a	A	G	11: 51,733,763		probably benign	Het
Shf	G	A	2: 122,368,682	P51S	probably damaging	Het
Slitrk6	C	T	14: 110,750,552	M574I	probably benign	Het
Slk	T	C	19: 47,622,677	F861L	probably damaging	Het
Smpd3	C	A	8: 106,264,971	A317S	probably benign	Het
Spz1	T	A	13: 92,575,125	Q281L	probably damaging	Het
Syde1	T	A	10: 78,586,980	R519S	probably benign	Het
Taf4	T	C	2: 179,976,531	H39R	unknown	Het
Tbx5	A	T	5: 119,845,113		probably null	Het
Tenm2	C	T	11: 36,063,177	G1236R	possibly damaging	Het
Th	G	A	7: 142,898,166	Q19*	probably null	Het
Tmprss11a	T	A	5: 86,420,179	I230F	probably damaging	Het
Tnfrsf14	T	A	4: 154,925,322	H50L	possibly damaging	Het
Tpp2	T	A	1: 43,978,725		probably null	Het
Trappc9	G	A	15: 73,025,967	R377W	probably damaging	Het
Trim2	A	G	3: 84,190,800	I398T	possibly damaging	Het
Trpc5	A	T	X: 144,481,226	S212T	probably damaging	Het
Ttn	A	G	2: 76,787,334		probably benign	Het
Unc80	A	G	1: 66,639,248	T2063A	possibly damaging	Het
Usp37	A	T	1: 74,479,655	S260T	probably benign	Het
Vcan	A	G	13: 89,691,681	S1915P	probably benign	Het
Vmn1r33	T	A	6: 66,612,298	I91F	possibly damaging	Het
Zfp422	T	C	6: 116,626,424	T205A	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
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
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
R6151:Diaph1	UTSW	18	37853353	missense	probably damaging	1.00
R6823:Diaph1	UTSW	18	37876383	intron	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	intron	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

Predicted Primers

PCR Primer
(F):5'- AAGGTGTCTCCGTGACAGCAATG -3'
(R):5'- TTTTACTGCGAGGACCAGAGCCAG -3'

Sequencing Primer
(F):5'- GCAGCTTATCTGTAAGGTTTACTTC -3'
(R):5'- CAGAGCCAGCGTGAGTCAG -3'

Posted On

2014-05-23