Mutagenetix > Incidental Mutation

Incidental Mutation 'R0920:Clock'

82813

Institutional Source

Beutler Lab

Gene Symbol

Clock

Ensembl Gene

ENSMUSG00000029238

Gene Name

clock circadian regulator

Synonyms

bHLHe8, KAT13D, 5330400M04Rik

MMRRC Submission

039070-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.794) question?

Stock #

R0920 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

76357715-76452639 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 76378167 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 578 (S578T)

Ref Sequence

ENSEMBL: ENSMUSP00000144022 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000075159] [ENSMUST00000202122] [ENSMUST00000202651]

AlphaFold

O08785

Predicted Effect

possibly damaging
Transcript: ENSMUST00000075159
AA Change: S578T

PolyPhen 2 Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000074656
Gene: ENSMUSG00000029238
AA Change: S578T

Domain	Start	End	E-Value	Type
HLH	40	90	7.77e-12	SMART
PAS	109	175	1.88e-6	SMART
PAS	264	330	3.65e-4	SMART
PAC	336	379	7.63e-7	SMART
low complexity region	426	446	N/A	INTRINSIC
low complexity region	478	493	N/A	INTRINSIC
coiled coil region	523	559	N/A	INTRINSIC
low complexity region	619	634	N/A	INTRINSIC
low complexity region	640	657	N/A	INTRINSIC
low complexity region	738	796	N/A	INTRINSIC
low complexity region	818	837	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000201768

Predicted Effect

possibly damaging
Transcript: ENSMUST00000202122
AA Change: S578T

PolyPhen 2 Score 0.798 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000144022
Gene: ENSMUSG00000029238
AA Change: S578T

Domain	Start	End	E-Value	Type
TFS2N	34	106	4.1e-3	SMART
HLH	40	90	3.4e-14	SMART
PAS	109	175	9.6e-9	SMART
PAS	264	330	1.8e-6	SMART
PAC	336	379	3.9e-9	SMART
low complexity region	426	446	N/A	INTRINSIC
low complexity region	478	493	N/A	INTRINSIC
coiled coil region	523	559	N/A	INTRINSIC
low complexity region	619	633	N/A	INTRINSIC
low complexity region	639	656	N/A	INTRINSIC
low complexity region	737	795	N/A	INTRINSIC
low complexity region	817	836	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000202651
AA Change: S578T

PolyPhen 2 Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000143939
Gene: ENSMUSG00000029238
AA Change: S578T

Domain	Start	End	E-Value	Type
HLH	40	90	7.77e-12	SMART
PAS	109	175	1.88e-6	SMART
PAS	264	330	3.65e-4	SMART
PAC	336	379	7.63e-7	SMART
low complexity region	426	446	N/A	INTRINSIC
low complexity region	478	493	N/A	INTRINSIC
coiled coil region	523	559	N/A	INTRINSIC
low complexity region	619	634	N/A	INTRINSIC
low complexity region	640	657	N/A	INTRINSIC
low complexity region	738	796	N/A	INTRINSIC
low complexity region	818	837	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000202857

Meta Mutation Damage Score

0.0606

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.6%
20x: 95.9%

Validation Efficiency

100% (37/37)

MGI Phenotype

FUNCTION: The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with Arntl (Bmal1) that binds E-box enhancer elements upstream of Period (Per1, Per2, Per3) and Cryptochrome (Cry1, Cry2) genes and activates transcription of these genes. Per and Cry proteins heterodimerize and repress their own transcription by interacting in a feedback loop with Clock/Arntl complexes. Polymorphisms in this gene may be associated with behavioral changes, obesity, and metabolic syndrome. Two transcripts encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit abnormal circadian phase. Mice homozygous for a spontaneous mutation exhibit abnormal circadian rhythm, reproduction, behavior, hair cycle, macronutrient absorption, and metabolism. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 36 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadacl4fm2	T	C	4: 144,287,696 (GRCm39)		probably benign	Het
Adamts16	A	G	13: 70,911,680 (GRCm39)		probably benign	Het
Adgra3	A	G	5: 50,118,503 (GRCm39)	V1015A	probably benign	Het
Armc5	G	T	7: 127,839,491 (GRCm39)	A270S	probably damaging	Het
Cacng1	A	C	11: 107,596,682 (GRCm39)		probably benign	Het
Ccdc33	T	C	9: 57,940,955 (GRCm39)	D429G	probably damaging	Het
Ccdc88b	G	T	19: 6,824,017 (GRCm39)	A1412E	probably benign	Het
Cfap298	C	T	16: 90,724,267 (GRCm39)	E125K	probably damaging	Het
Crp	T	C	1: 172,526,089 (GRCm39)	F58S	probably damaging	Het
Dlg5	T	A	14: 24,226,465 (GRCm39)	Q125L	probably damaging	Het
Eif3i	T	C	4: 129,489,050 (GRCm39)		probably benign	Het
Gucy1a2	A	C	9: 3,759,472 (GRCm39)	D426A	probably damaging	Het
Hpcal1	C	T	12: 17,841,098 (GRCm39)		probably benign	Het
Inf2	T	A	12: 112,576,721 (GRCm39)		probably benign	Het
Kdm7a	A	G	6: 39,128,256 (GRCm39)	L525P	probably damaging	Het
Kirrel3	A	T	9: 34,939,648 (GRCm39)	I152F	probably damaging	Het
Knl1	T	A	2: 118,900,309 (GRCm39)	I670K	probably benign	Het
Krt76	T	C	15: 101,800,874 (GRCm39)	T141A	possibly damaging	Het
Ldb3	T	C	14: 34,289,460 (GRCm39)	T249A	probably benign	Het
Magi3	A	T	3: 103,941,507 (GRCm39)		probably null	Het
Mfn1	A	G	3: 32,588,385 (GRCm39)		probably null	Het
Myb	G	T	10: 21,002,133 (GRCm39)	T736K	possibly damaging	Het
Myo5b	A	C	18: 74,758,712 (GRCm39)	K231T	probably benign	Het
Myt1l	T	A	12: 29,936,138 (GRCm39)	C909S	unknown	Het
Npas4	C	A	19: 5,036,344 (GRCm39)	E607*	probably null	Het
Nphp3	A	G	9: 103,909,106 (GRCm39)	N772S	probably benign	Het
Nup88	G	T	11: 70,847,146 (GRCm39)	P288Q	possibly damaging	Het
Or2l13	A	T	16: 19,305,680 (GRCm39)	I31F	probably benign	Het
Pknox1	C	A	17: 31,815,865 (GRCm39)	Q240K	probably damaging	Het
Plce1	A	C	19: 38,724,965 (GRCm39)	T1439P	probably damaging	Het
Ppp1r42	T	A	1: 10,069,750 (GRCm39)	N104I	probably damaging	Het
Prkar2a	T	A	9: 108,596,496 (GRCm39)		probably benign	Het
Stox2	C	T	8: 47,646,053 (GRCm39)	R469Q	probably damaging	Het
Syna	A	G	5: 134,587,956 (GRCm39)	V331A	probably benign	Het
Vmn1r58	A	T	7: 5,413,788 (GRCm39)	N147K	probably benign	Het
Zdhhc6	A	T	19: 55,300,133 (GRCm39)	L148H	probably damaging	Het

Other mutations in Clock

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00598:Clock	APN	5	76,377,311 (GRCm39)	missense	probably benign	0.17
IGL00725:Clock	APN	5	76,402,260 (GRCm39)	nonsense	probably null
IGL01304:Clock	APN	5	76,414,202 (GRCm39)	critical splice donor site	probably null
IGL01369:Clock	APN	5	76,384,933 (GRCm39)	missense	probably benign	0.30
IGL01542:Clock	APN	5	76,379,322 (GRCm39)	missense	possibly damaging	0.82
IGL02541:Clock	APN	5	76,410,519 (GRCm39)	splice site	probably null
IGL02602:Clock	APN	5	76,402,274 (GRCm39)	missense	probably damaging	1.00
IGL02602:Clock	APN	5	76,402,273 (GRCm39)	missense	probably null	1.00
IGL03186:Clock	APN	5	76,390,929 (GRCm39)	missense	probably damaging	0.98
IGL03309:Clock	APN	5	76,379,241 (GRCm39)	critical splice donor site	probably null
R6760_Clock_188	UTSW	5	76,374,823 (GRCm39)	missense	unknown
uhr	UTSW	5	76,377,401 (GRCm39)	nonsense	probably null
R0304:Clock	UTSW	5	76,374,832 (GRCm39)	missense	unknown
R0593:Clock	UTSW	5	76,413,683 (GRCm39)	missense	probably benign	0.25
R0654:Clock	UTSW	5	76,374,976 (GRCm39)	missense	possibly damaging	0.95
R0684:Clock	UTSW	5	76,393,365 (GRCm39)	missense	probably damaging	0.96
R0707:Clock	UTSW	5	76,374,976 (GRCm39)	missense	possibly damaging	0.95
R0751:Clock	UTSW	5	76,377,208 (GRCm39)	missense	possibly damaging	0.75
R0865:Clock	UTSW	5	76,414,271 (GRCm39)	splice site	probably benign
R1396:Clock	UTSW	5	76,414,649 (GRCm39)	missense	probably benign	0.00
R1450:Clock	UTSW	5	76,410,578 (GRCm39)	nonsense	probably null
R1487:Clock	UTSW	5	76,414,201 (GRCm39)	splice site	probably null
R1574:Clock	UTSW	5	76,390,679 (GRCm39)	missense	probably damaging	1.00
R1574:Clock	UTSW	5	76,390,679 (GRCm39)	missense	probably damaging	1.00
R1858:Clock	UTSW	5	76,388,756 (GRCm39)	missense	possibly damaging	0.92
R1872:Clock	UTSW	5	76,396,309 (GRCm39)	missense	possibly damaging	0.67
R1905:Clock	UTSW	5	76,414,735 (GRCm39)	splice site	probably benign
R1937:Clock	UTSW	5	76,377,340 (GRCm39)	missense	probably damaging	0.99
R2411:Clock	UTSW	5	76,379,360 (GRCm39)	missense	probably benign	0.08
R2887:Clock	UTSW	5	76,393,120 (GRCm39)	missense	probably damaging	0.99
R3410:Clock	UTSW	5	76,377,401 (GRCm39)	nonsense	probably null
R4514:Clock	UTSW	5	76,378,046 (GRCm39)	missense	probably benign	0.00
R4598:Clock	UTSW	5	76,383,657 (GRCm39)	missense	probably benign	0.00
R4599:Clock	UTSW	5	76,383,657 (GRCm39)	missense	probably benign	0.00
R4795:Clock	UTSW	5	76,413,763 (GRCm39)	missense	probably damaging	1.00
R4796:Clock	UTSW	5	76,413,763 (GRCm39)	missense	probably damaging	1.00
R4973:Clock	UTSW	5	76,402,258 (GRCm39)	missense	possibly damaging	0.62
R5204:Clock	UTSW	5	76,391,017 (GRCm39)	splice site	probably null
R5271:Clock	UTSW	5	76,389,801 (GRCm39)	missense	probably damaging	1.00
R5547:Clock	UTSW	5	76,378,185 (GRCm39)	missense	probably benign	0.02
R5630:Clock	UTSW	5	76,378,185 (GRCm39)	missense	probably benign	0.02
R5631:Clock	UTSW	5	76,378,185 (GRCm39)	missense	probably benign	0.02
R5632:Clock	UTSW	5	76,378,185 (GRCm39)	missense	probably benign	0.02
R5787:Clock	UTSW	5	76,384,898 (GRCm39)	missense	probably damaging	1.00
R6274:Clock	UTSW	5	76,385,000 (GRCm39)	missense	probably benign	0.45
R6578:Clock	UTSW	5	76,364,556 (GRCm39)	missense	unknown
R6622:Clock	UTSW	5	76,389,801 (GRCm39)	missense	probably damaging	1.00
R6760:Clock	UTSW	5	76,374,823 (GRCm39)	missense	unknown
R6793:Clock	UTSW	5	76,384,967 (GRCm39)	frame shift	probably null
R7406:Clock	UTSW	5	76,414,692 (GRCm39)	start codon destroyed	probably null	0.26
R7414:Clock	UTSW	5	76,410,611 (GRCm39)	missense	probably benign	0.00
R7560:Clock	UTSW	5	76,390,738 (GRCm39)	splice site	probably null
R7593:Clock	UTSW	5	76,384,145 (GRCm39)	missense	possibly damaging	0.80
R7640:Clock	UTSW	5	76,396,225 (GRCm39)	missense	possibly damaging	0.71
R7708:Clock	UTSW	5	76,414,256 (GRCm39)	missense	probably benign	0.00
R7713:Clock	UTSW	5	76,393,267 (GRCm39)	critical splice donor site	probably null
R7807:Clock	UTSW	5	76,390,982 (GRCm39)	missense	probably benign	0.01
R8171:Clock	UTSW	5	76,414,261 (GRCm39)	missense	possibly damaging	0.94
R8190:Clock	UTSW	5	76,375,051 (GRCm39)	missense	probably damaging	0.98
R8225:Clock	UTSW	5	76,389,759 (GRCm39)	missense	probably damaging	0.99
R8309:Clock	UTSW	5	76,402,269 (GRCm39)	missense	probably benign	0.07
R8557:Clock	UTSW	5	76,377,217 (GRCm39)	missense	probably damaging	1.00
R8792:Clock	UTSW	5	76,410,574 (GRCm39)	missense	probably damaging	1.00
R8869:Clock	UTSW	5	76,374,889 (GRCm39)	small deletion	probably benign
R8870:Clock	UTSW	5	76,383,632 (GRCm39)	missense	probably benign	0.17
R8980:Clock	UTSW	5	76,402,286 (GRCm39)	missense	probably benign	0.01
R8982:Clock	UTSW	5	76,364,559 (GRCm39)	missense	unknown
R9177:Clock	UTSW	5	76,377,256 (GRCm39)	missense	probably benign	0.00
R9208:Clock	UTSW	5	76,384,871 (GRCm39)	missense	probably benign	0.00
R9213:Clock	UTSW	5	76,393,376 (GRCm39)	missense	possibly damaging	0.94
R9307:Clock	UTSW	5	76,364,671 (GRCm39)	missense	unknown
R9446:Clock	UTSW	5	76,396,288 (GRCm39)	missense	probably benign	0.00
R9516:Clock	UTSW	5	76,377,227 (GRCm39)	missense	possibly damaging	0.85
R9572:Clock	UTSW	5	76,377,338 (GRCm39)	missense	probably benign	0.00
R9630:Clock	UTSW	5	76,393,281 (GRCm39)	missense	probably benign	0.03

Predicted Primers

PCR Primer
(F):5'- ATGCGAGCTACAAGAACTTGGTACAAT -3'
(R):5'- TCTGAGGAGCACTGAGGAACACA -3'

Sequencing Primer
(F):5'- taaaaaaataaaGGCTGGTACAACAC -3'
(R):5'- ttttgttgtcttgtttcttgtttttg -3'

Posted On

2013-11-08