Mutagenetix > Incidental Mutation

Incidental Mutation 'D4043:Chd7'

260

Institutional Source

Beutler Lab

Gene Symbol

Chd7

Ensembl Gene

ENSMUSG00000041235

Gene Name

chromodomain helicase DNA binding protein 7

Synonyms

Whi, Dz, Cyn, GENA 47, Cycn, Lda, Flo, Obt, Edy, A730019I05Rik, Todo, GENA 60, WBE1, Gena 52, Mt

Accession Numbers

Essential gene?

Probably essential (E-score: 0.952) question?

Stock #

D4043 (G3) of strain 483

Quality Score

Status

Validated

Chromosome

Chromosomal Location

8690406-8867659 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 8862650 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 2579 (D2579G)

Ref Sequence

ENSEMBL: ENSMUSP00000059079 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000039267] [ENSMUST00000051558] [ENSMUST00000170391]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000039267
AA Change: D2579G

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000043903
Gene: ENSMUSG00000041235
AA Change: D2579G

Domain	Start	End	E-Value	Type
low complexity region	11	28	N/A	INTRINSIC
low complexity region	48	59	N/A	INTRINSIC
low complexity region	107	129	N/A	INTRINSIC
low complexity region	152	178	N/A	INTRINSIC
low complexity region	194	206	N/A	INTRINSIC
low complexity region	385	400	N/A	INTRINSIC
low complexity region	491	504	N/A	INTRINSIC
low complexity region	512	535	N/A	INTRINSIC
low complexity region	585	595	N/A	INTRINSIC
low complexity region	632	696	N/A	INTRINSIC
low complexity region	721	733	N/A	INTRINSIC
low complexity region	735	748	N/A	INTRINSIC
low complexity region	759	768	N/A	INTRINSIC
CHROMO	789	854	2.54e-9	SMART
CHROMO	870	927	2.94e-5	SMART
low complexity region	928	939	N/A	INTRINSIC
DEXDc	954	1155	9.64e-38	SMART
HELICc	1310	1394	1.67e-23	SMART
Blast:DEXDc	1608	1653	8e-16	BLAST
low complexity region	1728	1739	N/A	INTRINSIC
internal_repeat_2	1774	1825	1.31e-5	PROSPERO
low complexity region	1831	1846	N/A	INTRINSIC
low complexity region	1898	1906	N/A	INTRINSIC
low complexity region	1929	1947	N/A	INTRINSIC
SANT	1952	2011	9.31e-1	SMART
internal_repeat_2	2079	2126	1.31e-5	PROSPERO
low complexity region	2173	2195	N/A	INTRINSIC
low complexity region	2218	2244	N/A	INTRINSIC
low complexity region	2387	2407	N/A	INTRINSIC
low complexity region	2437	2452	N/A	INTRINSIC
BRK	2553	2602	6.57e-23	SMART
BRK	2631	2675	3.77e-23	SMART
low complexity region	2715	2725	N/A	INTRINSIC
low complexity region	2746	2758	N/A	INTRINSIC
low complexity region	2769	2778	N/A	INTRINSIC
low complexity region	2785	2796	N/A	INTRINSIC
low complexity region	2810	2821	N/A	INTRINSIC
low complexity region	2897	2916	N/A	INTRINSIC
low complexity region	2967	2980	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000051558
AA Change: D2579G

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000059079
Gene: ENSMUSG00000041235
AA Change: D2579G

Domain	Start	End	E-Value	Type
low complexity region	11	28	N/A	INTRINSIC
low complexity region	48	59	N/A	INTRINSIC
low complexity region	107	129	N/A	INTRINSIC
low complexity region	152	178	N/A	INTRINSIC
low complexity region	194	206	N/A	INTRINSIC
low complexity region	385	400	N/A	INTRINSIC
low complexity region	491	504	N/A	INTRINSIC
low complexity region	512	535	N/A	INTRINSIC
low complexity region	585	595	N/A	INTRINSIC
low complexity region	632	696	N/A	INTRINSIC
low complexity region	721	733	N/A	INTRINSIC
low complexity region	735	748	N/A	INTRINSIC
low complexity region	759	768	N/A	INTRINSIC
CHROMO	789	854	2.54e-9	SMART
CHROMO	870	927	2.94e-5	SMART
low complexity region	928	939	N/A	INTRINSIC
DEXDc	954	1155	9.64e-38	SMART
HELICc	1310	1394	1.67e-23	SMART
Blast:DEXDc	1608	1653	8e-16	BLAST
low complexity region	1728	1739	N/A	INTRINSIC
internal_repeat_2	1774	1825	1.31e-5	PROSPERO
low complexity region	1831	1846	N/A	INTRINSIC
low complexity region	1898	1906	N/A	INTRINSIC
low complexity region	1929	1947	N/A	INTRINSIC
SANT	1952	2011	9.31e-1	SMART
internal_repeat_2	2079	2126	1.31e-5	PROSPERO
low complexity region	2173	2195	N/A	INTRINSIC
low complexity region	2218	2244	N/A	INTRINSIC
low complexity region	2387	2407	N/A	INTRINSIC
low complexity region	2437	2452	N/A	INTRINSIC
BRK	2553	2602	6.57e-23	SMART
BRK	2631	2675	3.77e-23	SMART
low complexity region	2715	2725	N/A	INTRINSIC
low complexity region	2746	2758	N/A	INTRINSIC
low complexity region	2769	2778	N/A	INTRINSIC
low complexity region	2785	2796	N/A	INTRINSIC
low complexity region	2810	2821	N/A	INTRINSIC
low complexity region	2897	2916	N/A	INTRINSIC
low complexity region	2967	2980	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000170391

SMART Domains

Protein: ENSMUSP00000127007
Gene: ENSMUSG00000041235

Domain	Start	End	E-Value	Type
low complexity region	11	28	N/A	INTRINSIC
low complexity region	48	59	N/A	INTRINSIC
low complexity region	107	129	N/A	INTRINSIC
low complexity region	152	178	N/A	INTRINSIC
low complexity region	194	206	N/A	INTRINSIC
low complexity region	385	400	N/A	INTRINSIC
low complexity region	491	504	N/A	INTRINSIC
low complexity region	512	535	N/A	INTRINSIC
BRK	586	630	3.77e-23	SMART
low complexity region	670	680	N/A	INTRINSIC
low complexity region	701	713	N/A	INTRINSIC
low complexity region	724	733	N/A	INTRINSIC
low complexity region	740	751	N/A	INTRINSIC
low complexity region	765	776	N/A	INTRINSIC
low complexity region	852	871	N/A	INTRINSIC
low complexity region	922	935	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000222546

Meta Mutation Damage Score

0.4037

Coding Region Coverage

1x: 88.8%
3x: 72.5%

Validation Efficiency

88% (220/249)

MGI Phenotype

FUNCTION: This gene encodes a protein containing two chromodomains and an ATP-binding helicase domain that functions as a regulator of transcription. Mutations in this gene result in an array of development defects, including inner ear problems. Mice defective for this gene exhibit many of the clinical features of the CHARGE syndrome caused by mutations in the homologous gene in human. [provided by RefSeq, Sep 2015]
PHENOTYPE: Heterozygotes for mutations of this gene exhibit a variety of combinations of hyperactivity, circling, head-bobbing, semicircular canal defects, hearing loss, reduced size, and tail-kink. [provided by MGI curators]

Allele List at MGI

All alleles(32) : Targeted, other(4) Gene trapped(19) Chemically induced(9)

Other mutations in this stock

Total: 25 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam29	A	T	8: 56,325,496 (GRCm39)	C319*	probably null	Het
Adgrg1	T	C	8: 95,731,857 (GRCm39)		probably null	Homo
Ago3	A	T	4: 126,244,796 (GRCm39)	V630E	probably damaging	Het
Armc8	G	T	9: 99,366,029 (GRCm39)	N628K	probably benign	Het
Cfap96	A	G	8: 46,409,440 (GRCm39)	V293A	probably damaging	Het
Duox1	G	A	2: 122,175,276 (GRCm39)	C1358Y	probably benign	Het
Ftsj3	C	A	11: 106,145,634 (GRCm39)	M66I	possibly damaging	Homo
Iqub	C	T	6: 24,505,750 (GRCm39)	E53K	possibly damaging	Het
Kirrel1	T	A	3: 86,990,510 (GRCm39)	T771S	probably benign	Het
Lrrc66	A	T	5: 73,764,869 (GRCm39)	S725T	probably benign	Het
Mael	T	C	1: 166,064,455 (GRCm39)	I104M	probably benign	Homo
Mkks	C	T	2: 136,716,530 (GRCm39)	V457I	probably benign	Het
Nadk2	T	A	15: 9,103,473 (GRCm39)		probably benign	Homo
Npas1	T	C	7: 16,197,169 (GRCm39)		probably null	Het
Ocrl	T	C	X: 47,025,200 (GRCm39)	V359A	probably benign	Homo
Or8k27	G	A	2: 86,275,564 (GRCm39)	T254M	probably damaging	Het
Pde6b	C	T	5: 108,573,222 (GRCm39)	R531*	probably null	Het
Polr1a	G	A	6: 71,918,401 (GRCm39)	C653Y	possibly damaging	Het
Rbm26	A	G	14: 105,389,976 (GRCm39)	V216A	possibly damaging	Het
Rin2	C	A	2: 145,664,283 (GRCm39)	H52Q	possibly damaging	Het
Ssc5d	C	T	7: 4,946,982 (GRCm39)	T1112I	possibly damaging	Het
Sv2c	C	T	13: 96,224,989 (GRCm39)	V107M	probably benign	Het
Tasor	A	G	14: 27,193,949 (GRCm39)	I1050V	probably benign	Het
Tulp3	G	A	6: 128,301,113 (GRCm39)	S366L	probably benign	Het
Zfp831	T	A	2: 174,487,059 (GRCm39)	V578E	probably benign	Homo

Other mutations in Chd7

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00422:Chd7	APN	4	8,859,106 (GRCm39)	missense	probably damaging	1.00
IGL00510:Chd7	APN	4	8,801,404 (GRCm39)	missense	probably damaging	1.00
IGL00741:Chd7	APN	4	8,839,454 (GRCm39)	missense	probably damaging	1.00
IGL00796:Chd7	APN	4	8,847,271 (GRCm39)	missense	possibly damaging	0.95
IGL00907:Chd7	APN	4	8,840,435 (GRCm39)	missense	probably damaging	0.98
IGL00930:Chd7	APN	4	8,805,181 (GRCm39)	missense	probably damaging	1.00
IGL01542:Chd7	APN	4	8,859,285 (GRCm39)	missense	possibly damaging	0.71
IGL01602:Chd7	APN	4	8,833,834 (GRCm39)	missense	probably damaging	1.00
IGL01605:Chd7	APN	4	8,833,834 (GRCm39)	missense	probably damaging	1.00
IGL01670:Chd7	APN	4	8,827,033 (GRCm39)	missense	probably damaging	0.98
IGL02434:Chd7	APN	4	8,752,145 (GRCm39)	missense	probably benign	0.00
IGL02531:Chd7	APN	4	8,854,134 (GRCm39)	missense	probably damaging	1.00
IGL02626:Chd7	APN	4	8,826,519 (GRCm39)	missense	probably damaging	1.00
IGL02961:Chd7	APN	4	8,751,542 (GRCm39)	missense	probably damaging	1.00
IGL02972:Chd7	APN	4	8,855,174 (GRCm39)	missense	probably benign	0.30
IGL03329:Chd7	APN	4	8,841,108 (GRCm39)	missense	probably damaging	1.00
Fili	UTSW	4	8,839,523 (GRCm39)	missense	probably damaging	1.00
IGL02991:Chd7	UTSW	4	8,828,398 (GRCm39)	missense	possibly damaging	0.91
PIT4466001:Chd7	UTSW	4	8,753,101 (GRCm39)	missense	unknown
PIT4472001:Chd7	UTSW	4	8,753,101 (GRCm39)	missense	unknown
R0157:Chd7	UTSW	4	8,833,759 (GRCm39)	missense	probably damaging	1.00
R0179:Chd7	UTSW	4	8,862,516 (GRCm39)	missense	probably benign	0.22
R0240:Chd7	UTSW	4	8,852,670 (GRCm39)	unclassified	probably benign
R0388:Chd7	UTSW	4	8,854,560 (GRCm39)	missense	probably benign	0.27
R0462:Chd7	UTSW	4	8,850,821 (GRCm39)	missense	probably damaging	1.00
R0512:Chd7	UTSW	4	8,805,139 (GRCm39)	intron	probably benign
R0657:Chd7	UTSW	4	8,753,141 (GRCm39)	missense	probably damaging	1.00
R0799:Chd7	UTSW	4	8,801,310 (GRCm39)	intron	probably benign
R0885:Chd7	UTSW	4	8,866,432 (GRCm39)	missense	probably damaging	1.00
R1056:Chd7	UTSW	4	8,822,402 (GRCm39)	missense	possibly damaging	0.50
R1086:Chd7	UTSW	4	8,866,458 (GRCm39)	missense	probably benign	0.04
R1353:Chd7	UTSW	4	8,839,556 (GRCm39)	missense	probably damaging	0.99
R1466:Chd7	UTSW	4	8,840,561 (GRCm39)	splice site	probably null
R1466:Chd7	UTSW	4	8,840,561 (GRCm39)	splice site	probably null
R1605:Chd7	UTSW	4	8,844,675 (GRCm39)	missense	probably damaging	1.00
R1693:Chd7	UTSW	4	8,864,307 (GRCm39)	critical splice donor site	probably null
R1695:Chd7	UTSW	4	8,833,960 (GRCm39)	missense	probably damaging	1.00
R1938:Chd7	UTSW	4	8,847,200 (GRCm39)	missense	probably damaging	1.00
R1964:Chd7	UTSW	4	8,865,978 (GRCm39)	missense	probably damaging	0.96
R2020:Chd7	UTSW	4	8,855,226 (GRCm39)	missense	probably benign	0.00
R2134:Chd7	UTSW	4	8,753,147 (GRCm39)	missense	probably damaging	0.99
R2171:Chd7	UTSW	4	8,752,424 (GRCm39)	missense	probably damaging	1.00
R2271:Chd7	UTSW	4	8,785,532 (GRCm39)	missense	probably damaging	1.00
R2300:Chd7	UTSW	4	8,855,241 (GRCm39)	missense	probably benign	0.02
R2355:Chd7	UTSW	4	8,801,350 (GRCm39)	missense	possibly damaging	0.95
R3153:Chd7	UTSW	4	8,855,174 (GRCm39)	missense	probably benign	0.30
R3430:Chd7	UTSW	4	8,844,517 (GRCm39)	missense	probably damaging	0.99
R3746:Chd7	UTSW	4	8,752,537 (GRCm39)	missense	probably damaging	1.00
R4118:Chd7	UTSW	4	8,865,831 (GRCm39)	missense	probably damaging	1.00
R4119:Chd7	UTSW	4	8,785,658 (GRCm39)	intron	probably benign
R4332:Chd7	UTSW	4	8,854,143 (GRCm39)	missense	probably damaging	1.00
R4402:Chd7	UTSW	4	8,866,353 (GRCm39)	missense	possibly damaging	0.61
R4571:Chd7	UTSW	4	8,866,217 (GRCm39)	missense	probably benign	0.09
R4722:Chd7	UTSW	4	8,822,445 (GRCm39)	missense	probably damaging	1.00
R4821:Chd7	UTSW	4	8,844,706 (GRCm39)	missense	probably damaging	1.00
R4894:Chd7	UTSW	4	8,838,629 (GRCm39)	missense	probably damaging	0.99
R5205:Chd7	UTSW	4	8,752,509 (GRCm39)	missense	possibly damaging	0.60
R5344:Chd7	UTSW	4	8,844,417 (GRCm39)	missense	probably damaging	1.00
R5484:Chd7	UTSW	4	8,828,258 (GRCm39)	missense	probably damaging	1.00
R5578:Chd7	UTSW	4	8,847,149 (GRCm39)	missense	probably benign	0.09
R5583:Chd7	UTSW	4	8,752,473 (GRCm39)	missense	probably damaging	1.00
R5888:Chd7	UTSW	4	8,866,382 (GRCm39)	missense	probably damaging	0.98
R5905:Chd7	UTSW	4	8,840,553 (GRCm39)	missense	possibly damaging	0.91
R6091:Chd7	UTSW	4	8,751,875 (GRCm39)	missense	probably damaging	0.99
R6126:Chd7	UTSW	4	8,826,482 (GRCm39)	missense	probably damaging	1.00
R6399:Chd7	UTSW	4	8,828,274 (GRCm39)	missense	probably damaging	1.00
R6751:Chd7	UTSW	4	8,833,866 (GRCm39)	missense	probably damaging	1.00
R6810:Chd7	UTSW	4	8,839,523 (GRCm39)	missense	probably damaging	1.00
R6868:Chd7	UTSW	4	8,811,501 (GRCm39)	splice site	probably null
R6952:Chd7	UTSW	4	8,856,797 (GRCm39)	missense	probably damaging	1.00
R6986:Chd7	UTSW	4	8,859,285 (GRCm39)	missense	possibly damaging	0.71
R6990:Chd7	UTSW	4	8,844,525 (GRCm39)	missense	probably benign	0.28
R7139:Chd7	UTSW	4	8,865,865 (GRCm39)	missense	probably benign	0.00
R7288:Chd7	UTSW	4	8,847,093 (GRCm39)	missense	possibly damaging	0.92
R7355:Chd7	UTSW	4	8,752,196 (GRCm39)	missense	unknown
R7452:Chd7	UTSW	4	8,854,731 (GRCm39)	missense	probably benign	0.03
R7471:Chd7	UTSW	4	8,859,197 (GRCm39)	missense	probably damaging	0.96
R7588:Chd7	UTSW	4	8,864,039 (GRCm39)	missense	probably damaging	1.00
R7711:Chd7	UTSW	4	8,805,234 (GRCm39)	missense	probably benign	0.00
R7744:Chd7	UTSW	4	8,862,485 (GRCm39)	splice site	probably null
R7842:Chd7	UTSW	4	8,854,115 (GRCm39)	missense	probably benign	0.01
R7883:Chd7	UTSW	4	8,826,504 (GRCm39)	missense	probably damaging	1.00
R7934:Chd7	UTSW	4	8,854,121 (GRCm39)	missense	probably benign	0.00
R7983:Chd7	UTSW	4	8,844,609 (GRCm39)	missense	possibly damaging	0.47
R7983:Chd7	UTSW	4	8,752,628 (GRCm39)	missense	unknown
R8022:Chd7	UTSW	4	8,751,605 (GRCm39)	missense	unknown
R8161:Chd7	UTSW	4	8,855,038 (GRCm39)	missense	probably damaging	1.00
R8274:Chd7	UTSW	4	8,839,432 (GRCm39)	missense	probably damaging	1.00
R8278:Chd7	UTSW	4	8,862,485 (GRCm39)	splice site	probably null
R8358:Chd7	UTSW	4	8,839,529 (GRCm39)	missense	probably damaging	1.00
R8464:Chd7	UTSW	4	8,811,465 (GRCm39)	missense	probably benign	0.06
R8483:Chd7	UTSW	4	8,822,412 (GRCm39)	missense	possibly damaging	0.65
R8507:Chd7	UTSW	4	8,858,675 (GRCm39)	missense	probably damaging	1.00
R8535:Chd7	UTSW	4	8,859,211 (GRCm39)	missense	possibly damaging	0.92
R8695:Chd7	UTSW	4	8,850,812 (GRCm39)	missense	probably damaging	1.00
R8700:Chd7	UTSW	4	8,833,892 (GRCm39)	missense	probably damaging	1.00
R8755:Chd7	UTSW	4	8,866,069 (GRCm39)	missense	probably benign	0.31
R8774:Chd7	UTSW	4	8,854,692 (GRCm39)	missense	probably damaging	1.00
R8774-TAIL:Chd7	UTSW	4	8,854,692 (GRCm39)	missense	probably damaging	1.00
R8796:Chd7	UTSW	4	8,838,691 (GRCm39)	missense	probably damaging	1.00
R8992:Chd7	UTSW	4	8,839,589 (GRCm39)	missense	probably damaging	1.00
R9018:Chd7	UTSW	4	8,847,083 (GRCm39)	missense	possibly damaging	0.88
R9122:Chd7	UTSW	4	8,840,510 (GRCm39)	missense	possibly damaging	0.77
R9131:Chd7	UTSW	4	8,785,642 (GRCm39)	missense
R9182:Chd7	UTSW	4	8,838,737 (GRCm39)	missense	probably damaging	1.00
R9227:Chd7	UTSW	4	8,805,272 (GRCm39)	missense	probably benign	0.03
R9254:Chd7	UTSW	4	8,752,210 (GRCm39)	missense	unknown
R9379:Chd7	UTSW	4	8,752,210 (GRCm39)	missense	unknown
R9388:Chd7	UTSW	4	8,865,756 (GRCm39)	missense	possibly damaging	0.89
R9455:Chd7	UTSW	4	8,752,061 (GRCm39)	missense	unknown
R9531:Chd7	UTSW	4	8,858,489 (GRCm39)	missense
R9577:Chd7	UTSW	4	8,752,964 (GRCm39)	missense	unknown
R9634:Chd7	UTSW	4	8,832,499 (GRCm39)	missense	probably damaging	1.00
Z1176:Chd7	UTSW	4	8,844,313 (GRCm39)	missense	probably damaging	1.00

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 8064 of the Chd7transcript in exon 35 of 38 total exons. Multiple transcripts of the Chd7 gene are displayed on Ensembl and Vega. The mutated nucleotide causes an aspartic acid to glycine substitution at amino acid 2579 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Chd7 gene encodes multiple isoforms of a transcriptional regulator that binds to chromatin. Isoform 1 contains 2986 amino acids with two Chromo domains at residues 790-857 and 872-937, a helicase ATP-binding domain at residues 970-1144, and a helicase C-terminal domain at residues 1284-1454. ATP binding occurs at amino acids 983-990 (Uniprot A2AJK6). CHD7 is essential for the formation of multipotent migratory neural crest, a transient cell population that is ectodermal in origin but undergoes a major transcriptional reprogramming event to acquire a remarkably broad differentiation potential and ability to migrate throughout the body, giving rise to craniofacial bones and cartilages, the peripheral nervous system, pigmentation, and cardiac structures. Heterozygote mice for mutations of this gene exhibit a variety of combinations of hyperactivity, circling, head-bobbing, semicircular canal defects, hearing loss, reduced size, and tail-kink. Human heterozygous mutations cause CHARGE syndrome (OMIM 214800), a pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina.

The D2579G change is predicted to be possibly damaging by the PolyPhen program.

Posted On

2010-08-09