Mutagenetix > Incidental Mutation

Incidental Mutation 'R1763:Dlk1'

193219

Institutional Source

Beutler Lab

Gene Symbol

Dlk1

Ensembl Gene

ENSMUSG00000040856

Gene Name

delta like non-canonical Notch ligand 1

Synonyms

SCP1, pref-1, pG2, Peg9, ZOG, DlkI, FA1

MMRRC Submission

039795-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.657) question?

Stock #

R1763 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

109418749-109429262 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 109424045 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Phenylalanine at position 102 (C102F)

Ref Sequence

ENSEMBL: ENSMUSP00000133530 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056110] [ENSMUST00000109841] [ENSMUST00000109842] [ENSMUST00000109843] [ENSMUST00000109844] [ENSMUST00000109846] [ENSMUST00000124293] [ENSMUST00000173539]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000056110
AA Change: C103F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000063104
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
EGF	213	247	4.06e-6	SMART
transmembrane domain	307	329	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000109841
AA Change: C103F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000105467
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
transmembrane domain	214	236	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000109842
AA Change: C103F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000105468
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
transmembrane domain	234	256	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000109843
AA Change: C103F

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000105469
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
transmembrane domain	212	234	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000109844
AA Change: C103F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000105470
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
EGF	213	247	4.06e-6	SMART
transmembrane domain	307	329	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000109846
AA Change: C103F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000105472
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
transmembrane domain	256	278	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000124293
AA Change: C102F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000133530
Gene: ENSMUSG00000040856
AA Change: C102F

Domain	Start	End	E-Value	Type
EGF	24	54	1.43e-1	SMART
EGF	55	85	1.26e-2	SMART
EGF_CA	87	124	1.77e-6	SMART
EGF	129	167	8.71e-6	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000173539
AA Change: C103F

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000133430
Gene: ENSMUSG00000040856
AA Change: C103F

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
EGF	25	55	1.43e-1	SMART
EGF	56	86	1.26e-2	SMART
EGF_CA	88	125	1.77e-6	SMART
EGF	130	168	8.71e-6	SMART
EGF	175	208	1.41e-5	SMART
transmembrane domain	232	254	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000174539

Predicted Effect

probably benign
Transcript: ENSMUST00000173812

SMART Domains

Protein: ENSMUSP00000134308
Gene: ENSMUSG00000040856

Domain	Start	End	E-Value	Type
SCOP:d1eqga2	2	15	4e-3	SMART
transmembrane domain	44	66	N/A	INTRINSIC

Meta Mutation Damage Score

0.9588

Coding Region Coverage

1x: 97.4%
3x: 96.8%
10x: 95.1%
20x: 92.0%

Validation Efficiency

98% (85/87)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal. [provided by RefSeq, Nov 2015]
PHENOTYPE: Homozygote null mice have reduced fetal growth and 50% lethality 2 days after birth. Survivors are small but have enlarged fat pad masses. Homozygotes for another null allele have abnormal B cell development. Paternally-inherited null alleles phenocopy homozygotes due to maternal imprinting. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadacl4fm4	A	G	4: 144,396,529 (GRCm39)	V401A	probably benign	Het
Abca4	G	A	3: 121,904,330 (GRCm39)	V794M	probably benign	Het
Abca4	A	T	3: 121,957,479 (GRCm39)	T772S	probably damaging	Het
Acox3	G	A	5: 35,765,683 (GRCm39)		probably null	Het
Adamts17	A	G	7: 66,797,463 (GRCm39)	N1060S	probably damaging	Het
Akap8l	C	T	17: 32,551,457 (GRCm39)	R511H	probably damaging	Het
Als2	T	C	1: 59,214,150 (GRCm39)	Y1346C	probably benign	Het
Apol10b	A	T	15: 77,469,215 (GRCm39)	F321I	probably benign	Het
Atp5pb	A	G	3: 105,858,905 (GRCm39)		probably null	Het
Bloc1s5	A	G	13: 38,803,060 (GRCm39)		probably benign	Het
Btbd9	T	C	17: 30,553,271 (GRCm39)	N397S	possibly damaging	Het
Cacna1d	A	G	14: 29,821,153 (GRCm39)	V1121A	probably benign	Het
Cad	G	A	5: 31,218,295 (GRCm39)	V460I	probably damaging	Het
Caprin2	A	T	6: 148,744,619 (GRCm39)	D935E	probably damaging	Het
Ccdc150	A	T	1: 54,393,795 (GRCm39)	K686N	probably benign	Het
Ccnt2	T	C	1: 127,727,143 (GRCm39)	F186L	possibly damaging	Het
Cd5l	G	A	3: 87,275,187 (GRCm39)		probably null	Het
Chrna7	A	G	7: 62,749,000 (GRCm39)	V494A	probably benign	Het
Clec2i	T	G	6: 128,872,388 (GRCm39)	Y198*	probably null	Het
Col22a1	A	G	15: 71,879,025 (GRCm39)	V44A	probably damaging	Het
Cspg4	T	A	9: 56,794,263 (GRCm39)	I666N	probably damaging	Het
Cyp3a16	A	T	5: 145,401,841 (GRCm39)		probably null	Het
Dscc1	CTGAATGAAT	CTGAAT	15: 54,943,572 (GRCm39)		probably benign	Het
Dscc1	T	A	15: 54,947,535 (GRCm39)	H215L	probably damaging	Het
Dus1l	C	G	11: 120,686,497 (GRCm39)	G15R	probably benign	Het
Eps8l1	G	T	7: 4,474,822 (GRCm39)	V268L	probably benign	Het
F2	A	C	2: 91,465,251 (GRCm39)	C104W	probably damaging	Het
F5	C	A	1: 164,020,104 (GRCm39)	Q860K	probably benign	Het
Fmn2	T	C	1: 174,329,832 (GRCm39)	L74P	unknown	Het
Frmd6	G	A	12: 70,940,396 (GRCm39)	R347Q	possibly damaging	Het
Gabbr1	T	G	17: 37,365,659 (GRCm39)	S158A	probably damaging	Het
Galc	T	C	12: 98,200,525 (GRCm39)	N295S	probably damaging	Het
Gm6408	A	T	5: 146,419,132 (GRCm39)	N49I	probably damaging	Het
Grm1	T	A	10: 10,955,610 (GRCm39)	T225S	possibly damaging	Het
Grm8	C	T	6: 27,285,866 (GRCm39)	V849I	possibly damaging	Het
Hmcn2	A	G	2: 31,204,602 (GRCm39)	D59G	probably damaging	Het
Iars1	G	A	13: 49,876,553 (GRCm39)		probably null	Het
Ifi27l2a	C	T	12: 103,403,941 (GRCm39)	A127V	possibly damaging	Het
Ikbip	A	G	10: 90,932,343 (GRCm39)	N329S	probably damaging	Het
Ikbke	T	C	1: 131,193,614 (GRCm39)	T479A	probably benign	Het
Krt12	T	A	11: 99,306,886 (GRCm39)	N472I	probably damaging	Het
Lmnb2	A	T	10: 80,743,025 (GRCm39)	L193Q	probably damaging	Het
Lrriq4	T	C	3: 30,704,401 (GRCm39)	V128A	probably benign	Het
Map4k4	C	A	1: 40,039,917 (GRCm39)		probably benign	Het
Mtmr7	T	C	8: 41,004,852 (GRCm39)	T575A	probably benign	Het
Myh13	G	A	11: 67,225,402 (GRCm39)	A256T	probably benign	Het
Napepld	A	G	5: 21,888,408 (GRCm39)	Y14H	probably benign	Het
Npr1	T	C	3: 90,366,644 (GRCm39)	T552A	probably damaging	Het
Nudt15	A	G	14: 73,759,087 (GRCm39)	F127S	probably benign	Het
Nwd2	T	A	5: 63,965,614 (GRCm39)	S1733T	probably benign	Het
Or11a4	T	C	17: 37,536,321 (GRCm39)	F102L	probably benign	Het
Or4c102	A	G	2: 88,422,780 (GRCm39)	I211V	probably benign	Het
Or4c10b	G	A	2: 89,711,473 (GRCm39)	G101E	probably damaging	Het
Or6z1	T	G	7: 6,504,440 (GRCm39)	I262L	probably benign	Het
Or8b44	A	G	9: 38,410,334 (GRCm39)	Y123C	probably damaging	Het
Paqr7	A	T	4: 134,234,409 (GRCm39)	I89F	probably benign	Het
Pidd1	C	A	7: 141,019,543 (GRCm39)	V706L	probably benign	Het
Polr3c	A	T	3: 96,620,911 (GRCm39)	I469N	probably damaging	Het
Ppip5k1	A	G	2: 121,179,028 (GRCm39)	Y233H	probably damaging	Het
Psmc3	A	G	2: 90,886,340 (GRCm39)	T166A	possibly damaging	Het
Ptchd3	A	T	11: 121,733,368 (GRCm39)	I753L	probably benign	Het
Rad21	T	C	15: 51,841,566 (GRCm39)	K50R	probably damaging	Het
Rad54b	A	G	4: 11,604,989 (GRCm39)	E479G	possibly damaging	Het
Rfwd3	C	T	8: 112,014,874 (GRCm39)	R326Q	probably damaging	Het
Rgs20	C	T	1: 4,980,863 (GRCm39)	R154Q	probably damaging	Het
Sbf1	T	C	15: 89,178,628 (GRCm39)	D1449G	probably damaging	Het
Sema4g	C	T	19: 44,990,044 (GRCm39)	R708*	probably null	Het
Septin9	T	C	11: 117,181,254 (GRCm39)	I18T	probably benign	Het
Serpinb6b	A	G	13: 33,162,041 (GRCm39)	E280G	probably damaging	Het
Slamf6	T	C	1: 171,770,154 (GRCm39)		probably benign	Het
Slc6a21	G	A	7: 44,937,158 (GRCm39)	W554*	probably null	Het
Slco1a4	A	C	6: 141,758,457 (GRCm39)	I518R	probably benign	Het
Stab1	T	A	14: 30,890,373 (GRCm39)	Q26L	probably benign	Het
Stox1	A	G	10: 62,503,744 (GRCm39)	F104L	probably damaging	Het
Suco	T	C	1: 161,662,518 (GRCm39)	K638E	possibly damaging	Het
Synpo	T	C	18: 60,735,856 (GRCm39)	K458E	probably damaging	Het
Szt2	A	T	4: 118,229,565 (GRCm39)	W2820R	unknown	Het
Tmtc1	C	A	6: 148,196,116 (GRCm39)	G499W	probably damaging	Het
Tonsl	A	C	15: 76,522,266 (GRCm39)	S242R	probably damaging	Het
Trpc4	G	T	3: 54,102,243 (GRCm39)	S47I	possibly damaging	Het
Zfp106	G	A	2: 120,350,909 (GRCm39)	R1581C	probably benign	Het
Zfp27	A	G	7: 29,594,801 (GRCm39)	L388P	possibly damaging	Het

Other mutations in Dlk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
R0041:Dlk1	UTSW	12	109,421,439 (GRCm39)	missense	probably damaging	1.00
R0379:Dlk1	UTSW	12	109,420,985 (GRCm39)	unclassified	probably benign
R1250:Dlk1	UTSW	12	109,425,744 (GRCm39)	missense	probably damaging	1.00
R1363:Dlk1	UTSW	12	109,421,430 (GRCm39)	missense	probably damaging	1.00
R1757:Dlk1	UTSW	12	109,425,613 (GRCm39)	missense	probably damaging	1.00
R1772:Dlk1	UTSW	12	109,425,685 (GRCm39)	missense	probably damaging	1.00
R2189:Dlk1	UTSW	12	109,420,975 (GRCm39)	critical splice donor site	probably null
R2334:Dlk1	UTSW	12	109,419,614 (GRCm39)	missense	probably damaging	0.96
R3751:Dlk1	UTSW	12	109,426,239 (GRCm39)	missense	probably benign	0.15
R5256:Dlk1	UTSW	12	109,425,697 (GRCm39)	missense	probably damaging	1.00
R5268:Dlk1	UTSW	12	109,425,764 (GRCm39)	missense	probably benign	0.34
R5356:Dlk1	UTSW	12	109,421,447 (GRCm39)	missense	probably damaging	0.99
R5669:Dlk1	UTSW	12	109,425,964 (GRCm39)	missense	probably benign	0.04
R5748:Dlk1	UTSW	12	109,425,898 (GRCm39)	missense	probably benign	0.00
R5992:Dlk1	UTSW	12	109,421,507 (GRCm39)	missense	probably damaging	1.00
R6076:Dlk1	UTSW	12	109,425,895 (GRCm39)	missense	probably damaging	0.98
R6539:Dlk1	UTSW	12	109,426,245 (GRCm39)	missense	probably benign	0.01
R6638:Dlk1	UTSW	12	109,426,204 (GRCm39)	missense	probably damaging	1.00
R7480:Dlk1	UTSW	12	109,421,540 (GRCm39)	missense	probably damaging	1.00
R7553:Dlk1	UTSW	12	109,420,889 (GRCm39)	missense	unknown
R7602:Dlk1	UTSW	12	109,421,551 (GRCm39)	critical splice donor site	probably null
R8531:Dlk1	UTSW	12	109,424,066 (GRCm39)	missense	probably null	0.06
R9120:Dlk1	UTSW	12	109,424,051 (GRCm39)	missense	probably benign	0.00
R9554:Dlk1	UTSW	12	109,420,889 (GRCm39)	missense	unknown
X0020:Dlk1	UTSW	12	109,425,838 (GRCm39)	missense	probably damaging	1.00
X0053:Dlk1	UTSW	12	109,426,063 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACTTGGAAATCACTAGCTGAGCCAC -3'
(R):5'- TGTCATTCACCAGCATTGGAGCC -3'

Sequencing Primer
(F):5'- ACTAGCTGAGCCACTTAGGG -3'
(R):5'- GGGGAGCACATCTTTCATCAG -3'

Posted On

2014-05-23