Mutagenetix > Incidental Mutation

Incidental Mutation 'R8905:Dhfr'

680051

Institutional Source

Beutler Lab

Gene Symbol

Dhfr

Ensembl Gene

ENSMUSG00000021707

Gene Name

dihydrofolate reductase

Synonyms

8430436I03Rik

MMRRC Submission

068762-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8905 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

92491291-92525561 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 92494467 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 57 (T57A)

Ref Sequence

ENSEMBL: ENSMUSP00000022218 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022218] [ENSMUST00000022220] [ENSMUST00000185852] [ENSMUST00000187424] [ENSMUST00000187874] [ENSMUST00000190393] [ENSMUST00000191509] [ENSMUST00000191550]

AlphaFold

P00375

PDB Structure

Understanding the Role of Leu22 Variants in Methotrexate Resistance: Comparison of Wild-type and Leu22Arg Variant Mouse and Human Dihydrofolate Reductase [X-RAY DIFFRACTION]
New Insights into DHFR Interactions: Analysis of Pneumocystis carinii and Mouse DHFR Complexes with NADPH and Two Highly Potent Trimethoprim Derivatives [X-RAY DIFFRACTION]
Structural Analysis of a Holo Enzyme Complex of Mouse Dihydrofolate Reductase with NADPH and a Ternary Complex wtih the Potent and Selective Inhibitor 2,4-Diamino-6-(2'-hydroxydibenz[b,f]azepin-5-yl)methylpteridine [X-RAY DIFFRACTION]
Structural Analysis of a Holo Enzyme Complex of Mouse Dihydrofolate Reductase with NADPH and a Ternary Complex with the Potent and Selective Inhibitor 2.4-Diamino-6-(-2'-hydroxydibenz[b,f]azepin-5-yl)methylpteridine [X-RAY DIFFRACTION]
Alternate Binding Modes Observed for the E- and Z-isomers of 2,4-Diaminofuro[2,3d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase [X-RAY DIFFRACTION]
Alternate Binding Modes Observed for the E- and Z-Isomers of 2,4-Diaminofuro[2,3-d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000022218
AA Change: T57A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000022218
Gene: ENSMUSG00000021707
AA Change: T57A

Domain	Start	End	E-Value	Type
Pfam:DHFR_1	4	185	3.9e-37	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000022220

SMART Domains

Protein: ENSMUSP00000022220
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC
Pfam:MutS_I	188	301	1.6e-35	PFAM
Pfam:MutS_II	324	481	2.2e-36	PFAM
MUTSd	513	828	7.62e-97	SMART
MUTSac	847	1049	9.7e-122	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000185852

SMART Domains

Protein: ENSMUSP00000140002
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC
Pfam:MutS_I	188	301	7.2e-35	PFAM
Pfam:MutS_II	324	481	2.2e-36	PFAM
MUTSd	513	828	7.62e-97	SMART
MUTSac	847	1049	9.7e-122	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000187424

SMART Domains

Protein: ENSMUSP00000139622
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000187874

SMART Domains

Protein: ENSMUSP00000139620
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000190393

SMART Domains

Protein: ENSMUSP00000141163
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC
Pfam:MutS_I	188	241	6.4e-10	PFAM
low complexity region	261	285	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000191509

SMART Domains

Protein: ENSMUSP00000141158
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000191550

SMART Domains

Protein: ENSMUSP00000140659
Gene: ENSMUSG00000014850

Domain	Start	End	E-Value	Type
low complexity region	4	19	N/A	INTRINSIC
low complexity region	24	40	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.3%

Validation Efficiency

100% (77/77)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit lethality soon after E14.5 with reduced size, pallor, impaired hematopoiesis and abnormal folic acid levels. Mice heterozygous for this allele exhibit abnormal folic acid levels, abnormal hemopoiesis and reduced endothelium-dependent vasorelaxation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700013G24Rik	T	C	4: 137,182,553 (GRCm39)	V236A	probably benign	Het
Abca15	A	T	7: 119,960,771 (GRCm39)	R744S	probably benign	Het
Adgra1	T	C	7: 139,455,763 (GRCm39)	S464P	probably damaging	Het
Arhgap45	T	C	10: 79,855,570 (GRCm39)	V3A	probably benign	Het
AW554918	T	A	18: 25,473,206 (GRCm39)	S134T	probably damaging	Het
Bmper	A	G	9: 23,318,082 (GRCm39)	E567G	probably benign	Het
C2cd3	T	C	7: 100,074,132 (GRCm39)		probably null	Het
Cars1	A	G	7: 143,140,196 (GRCm39)	Y170H	probably damaging	Het
Celsr1	A	T	15: 85,788,269 (GRCm39)		probably benign	Het
Celsr3	C	T	9: 108,718,501 (GRCm39)	H2351Y	probably damaging	Het
Cfap210	A	G	2: 69,612,104 (GRCm39)	S175P	probably benign	Het
Clxn	A	G	16: 14,738,275 (GRCm39)	I147V	possibly damaging	Het
Cyp2d11	T	C	15: 82,275,102 (GRCm39)	I282V	probably benign	Het
Dhrs7l	T	A	12: 72,666,431 (GRCm39)	D80V	probably damaging	Het
Dnah7b	A	C	1: 46,292,534 (GRCm39)	Q2973P	probably damaging	Het
Dnajc5b	T	C	3: 19,633,184 (GRCm39)	C136R	probably benign	Het
Ercc3	T	G	18: 32,398,771 (GRCm39)	D683E	possibly damaging	Het
Faxc	A	G	4: 21,982,398 (GRCm39)	Y279C	probably damaging	Het
Fbxw7	T	C	3: 84,872,634 (GRCm39)	M191T	possibly damaging	Het
Fcgbp	T	A	7: 27,785,934 (GRCm39)	V457E	probably damaging	Het
Fip1l1	A	T	5: 74,756,624 (GRCm39)	T539S	probably damaging	Het
Gabra1	T	C	11: 42,038,052 (GRCm39)	T189A	possibly damaging	Het
Glg1	T	C	8: 111,884,668 (GRCm39)	D1118G	probably damaging	Het
Gli3	A	G	13: 15,901,116 (GRCm39)	D1501G	probably benign	Het
Hacd1	A	G	2: 14,049,761 (GRCm39)	I91T	possibly damaging	Het
Ift22	T	C	5: 136,941,745 (GRCm39)	V159A	probably benign	Het
Igkv1-110	T	A	6: 68,248,070 (GRCm39)	Y60N	probably damaging	Het
Inpp5d	A	G	1: 87,637,348 (GRCm39)	K502E	probably damaging	Het
Kcnt2	A	T	1: 140,435,467 (GRCm39)	Q478L	possibly damaging	Het
Mettl13	A	G	1: 162,364,847 (GRCm39)	F511L	probably damaging	Het
Mis18bp1	T	C	12: 65,180,401 (GRCm39)		probably null	Het
Mrps30	A	T	13: 118,523,479 (GRCm39)	S98T	probably benign	Het
Muc2	C	T	7: 141,279,643 (GRCm39)	A209V	probably benign	Het
Nfs1	A	T	2: 155,970,503 (GRCm39)	I270N	probably damaging	Het
Nlgn3	T	C	X: 100,352,390 (GRCm39)	V179A	probably damaging	Het
Nsmaf	A	G	4: 6,424,951 (GRCm39)	S266P	probably benign	Het
Obscn	A	G	11: 58,960,784 (GRCm39)	S3176P	probably damaging	Het
Or4c123	A	T	2: 89,126,801 (GRCm39)	L271Q	possibly damaging	Het
Or7g12	A	G	9: 18,899,494 (GRCm39)	D70G	possibly damaging	Het
P2ry12	T	A	3: 59,124,997 (GRCm39)	Y226F	probably damaging	Het
Pabpc2	C	A	18: 39,907,704 (GRCm39)	T323K	probably benign	Het
Pank2	A	G	2: 131,124,646 (GRCm39)	D71G	possibly damaging	Het
Patj	A	T	4: 98,385,412 (GRCm39)	H393L	probably damaging	Het
Pde8b	A	G	13: 95,182,993 (GRCm39)	V255A	probably damaging	Het
Plekhs1	T	C	19: 56,471,028 (GRCm39)	W374R	probably damaging	Het
Ppm1g	T	C	5: 31,361,437 (GRCm39)	D313G	probably damaging	Het
Rnf114	A	G	2: 167,353,134 (GRCm39)	N135S	probably benign	Het
Rnf43	T	G	11: 87,621,951 (GRCm39)	Y351D	probably damaging	Het
Robo1	A	T	16: 72,539,173 (GRCm39)	D90V	probably damaging	Het
Sbds	A	G	5: 130,277,125 (GRCm39)	V172A	possibly damaging	Het
Scamp5	T	A	9: 57,352,669 (GRCm39)	I167F	probably benign	Het
Sec14l5	A	G	16: 4,994,364 (GRCm39)	E386G	probably damaging	Het
Sfxn1	T	A	13: 54,246,433 (GRCm39)	V159E	probably damaging	Het
Sgsm1	C	T	5: 113,421,495 (GRCm39)	G531R	probably benign	Het
Slc22a26	T	A	19: 7,760,331 (GRCm39)	I471F	probably damaging	Het
Slc41a3	T	A	6: 90,589,123 (GRCm39)	M78K	probably benign	Het
Slc8a1	A	T	17: 81,749,084 (GRCm39)	Y653N	probably benign	Het
Slco6c1	A	T	1: 97,053,391 (GRCm39)	M170K	possibly damaging	Het
Smarca5	A	T	8: 81,440,577 (GRCm39)	I629K	probably benign	Het
Smg7	T	A	1: 152,715,817 (GRCm39)	D1099V	probably damaging	Het
Spata31e2	A	G	1: 26,721,895 (GRCm39)	V1095A	probably damaging	Het
Srbd1	T	C	17: 86,308,890 (GRCm39)	I763V	probably benign	Het
Stk25	A	G	1: 93,556,929 (GRCm39)	S30P	probably damaging	Het
Sv2b	C	T	7: 74,767,459 (GRCm39)	A646T	probably benign	Het
Tardbp	T	C	4: 148,705,093 (GRCm39)	M167V	probably benign	Het
Tmem132a	T	C	19: 10,842,647 (GRCm39)	N276S	probably damaging	Het
Ttpa	T	A	4: 20,028,435 (GRCm39)	S162T	probably benign	Het
Usp13	T	C	3: 32,935,572 (GRCm39)	Y333H	probably damaging	Het
Vmn2r3	T	A	3: 64,166,695 (GRCm39)	Y812F	probably damaging	Het
Yeats2	A	G	16: 20,009,144 (GRCm39)	T463A	probably benign	Het
Zbtb26	T	A	2: 37,326,927 (GRCm39)	K36N	probably benign	Het
Zfc3h1	A	T	10: 115,259,383 (GRCm39)	T1652S	probably benign	Het
Zfp472	G	A	17: 33,197,455 (GRCm39)	C510Y	possibly damaging	Het
Zfp518a	C	A	19: 40,902,780 (GRCm39)	T903K	probably damaging	Het
Zfp668	T	C	7: 127,465,598 (GRCm39)	T529A	probably benign	Het
Zfp930	A	G	8: 69,681,351 (GRCm39)	T349A	possibly damaging	Het
Zmiz2	T	G	11: 6,346,840 (GRCm39)	Y182D	probably damaging	Het

Other mutations in Dhfr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01659:Dhfr	APN	13	92,492,178 (GRCm39)	splice site	probably null
R0546:Dhfr	UTSW	13	92,504,692 (GRCm39)	critical splice acceptor site	probably null
R1465:Dhfr	UTSW	13	92,504,815 (GRCm39)	splice site	probably benign
R2026:Dhfr	UTSW	13	92,502,279 (GRCm39)	nonsense	probably null
R4905:Dhfr	UTSW	13	92,502,282 (GRCm39)	missense	probably damaging	1.00
R5109:Dhfr	UTSW	13	92,491,788 (GRCm39)	missense	probably damaging	1.00
R7039:Dhfr	UTSW	13	92,491,791 (GRCm39)	missense	probably benign	0.04
R7869:Dhfr	UTSW	13	92,494,471 (GRCm39)	nonsense	probably null
R9509:Dhfr	UTSW	13	92,504,739 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GAACTGCATGAGCCAAACTG -3'
(R):5'- GTACCTGCCTACATACTCGTG -3'

Sequencing Primer
(F):5'- CTGCATGAGCCAAACTGAAAAATTG -3'
(R):5'- GCCTACATACTCGTGCACGC -3'

Posted On

2021-08-31