Mutagenetix > Incidental Mutation

Incidental Mutation 'R1250:Dlk1'

151729

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

039317-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.657) question?

Stock #

R1250 (G1)

Quality Score

140

Status

Not validated

Chromosome

Chromosomal Location

109418749-109429262 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 109425744 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Serine at position 206 (T206S)

Ref Sequence

ENSEMBL: ENSMUSP00000105472 (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: T206S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000063104
Gene: ENSMUSG00000040856
AA Change: T206S

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: T206S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105467
Gene: ENSMUSG00000040856
AA Change: T206S

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: T206S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105468
Gene: ENSMUSG00000040856
AA Change: T206S

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: T206S

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

SMART Domains

Protein: ENSMUSP00000105469
Gene: ENSMUSG00000040856
AA Change: T206S

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: T206S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105470
Gene: ENSMUSG00000040856
AA Change: T206S

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: T206S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105472
Gene: ENSMUSG00000040856
AA Change: T206S

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 benign
Transcript: ENSMUST00000124293

SMART Domains

Protein: ENSMUSP00000133530
Gene: ENSMUSG00000040856

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: T206S

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000133430
Gene: ENSMUSG00000040856
AA Change: T206S

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

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

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.5%
20x: 93.6%

Validation Efficiency

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: 19 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aptx	T	A	4: 40,693,447 (GRCm39)	E162D	probably benign	Het
Cdhr4	A	T	9: 107,874,715 (GRCm39)	Q20L	probably damaging	Het
Gabrr2	T	C	4: 33,063,273 (GRCm39)	L32P	probably benign	Het
Gjb3	G	A	4: 127,220,224 (GRCm39)	R103W	probably damaging	Het
Kntc1	T	A	5: 123,922,262 (GRCm39)	S954T	possibly damaging	Het
Krt28	A	G	11: 99,257,648 (GRCm39)		probably null	Het
Lingo3	T	C	10: 80,670,605 (GRCm39)	T442A	probably benign	Het
Map3k5	G	A	10: 19,986,521 (GRCm39)	A912T	possibly damaging	Het
Msantd3	C	A	4: 48,552,789 (GRCm39)	P126Q	probably damaging	Het
Nek10	T	C	14: 14,853,887 (GRCm38)	S358P	probably damaging	Het
Prl2c2	G	C	13: 13,176,786 (GRCm39)	T47R	probably damaging	Het
Prss59	A	T	6: 40,902,909 (GRCm39)		probably null	Het
Qtrt1	C	T	9: 21,330,844 (GRCm39)	T324M	probably benign	Het
Rag2	A	G	2: 101,460,784 (GRCm39)	S365G	probably damaging	Het
Slc6a2	C	A	8: 93,719,491 (GRCm39)	T402K	probably benign	Het
Slc9b1	T	C	3: 135,054,531 (GRCm39)	M1T	probably null	Het
Ttn	A	G	2: 76,720,904 (GRCm39)		probably benign	Het
Vmn1r31	A	G	6: 58,449,643 (GRCm39)	V74A	probably benign	Het
Zkscan3	A	G	13: 21,572,694 (GRCm39)	F313L	probably benign	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
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
R1763:Dlk1	UTSW	12	109,424,045 (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'- GTTAATAATGCTGCCTCTCCCAGCC -3'
(R):5'- GGACACCTTCAGGATGTGTTGCTC -3'

Sequencing Primer
(F):5'- GACTAGTGACTTACAATCTGTGCTC -3'
(R):5'- TGCTGAACAGGCAGCTC -3'

Posted On

2014-01-29