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

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

MMRRC Submission

039795-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.711) question?

Stock #

R1763 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

109452823-109463336 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 109458119 bp (GRCm38)

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

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000174539

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
Abca4	G	A	3: 122,110,681	V794M	probably benign	Het
Abca4	A	T	3: 122,163,830	T772S	probably damaging	Het
Acox3	G	A	5: 35,608,339		probably null	Het
Adamts17	A	G	7: 67,147,715	N1060S	probably damaging	Het
Akap8l	C	T	17: 32,332,483	R511H	probably damaging	Het
Als2	T	C	1: 59,174,991	Y1346C	probably benign	Het
Apol10b	A	T	15: 77,585,015	F321I	probably benign	Het
Atp5f1	A	G	3: 105,951,589		probably null	Het
Bloc1s5	A	G	13: 38,619,084		probably benign	Het
Btbd9	T	C	17: 30,334,297	N397S	possibly damaging	Het
Cacna1d	A	G	14: 30,099,196	V1121A	probably benign	Het
Cad	G	A	5: 31,060,951	V460I	probably damaging	Het
Caprin2	A	T	6: 148,843,121	D935E	probably damaging	Het
Ccdc150	A	T	1: 54,354,636	K686N	probably benign	Het
Ccnt2	T	C	1: 127,799,406	F186L	possibly damaging	Het
Cd5l	G	A	3: 87,367,880		probably null	Het
Chrna7	A	G	7: 63,099,252	V494A	probably benign	Het
Clec2i	T	G	6: 128,895,425	Y198*	probably null	Het
Col22a1	A	G	15: 72,007,176	V44A	probably damaging	Het
Cspg4	T	A	9: 56,886,979	I666N	probably damaging	Het
Cyp3a16	A	T	5: 145,465,031		probably null	Het
Dscc1	T	A	15: 55,084,139	H215L	probably damaging	Het
Dscc1	CTGAATGAAT	CTGAAT	15: 55,080,176		probably benign	Het
Dus1l	C	G	11: 120,795,671	G15R	probably benign	Het
Eps8l1	G	T	7: 4,471,823	V268L	probably benign	Het
F2	A	C	2: 91,634,906	C104W	probably damaging	Het
F5	C	A	1: 164,192,535	Q860K	probably benign	Het
Fmn2	T	C	1: 174,502,266	L74P	unknown	Het
Frmd6	G	A	12: 70,893,622	R347Q	possibly damaging	Het
Gabbr1	T	G	17: 37,054,767	S158A	probably damaging	Het
Galc	T	C	12: 98,234,266	N295S	probably damaging	Het
Gm436	A	G	4: 144,669,959	V401A	probably benign	Het
Gm6408	A	T	5: 146,482,322	N49I	probably damaging	Het
Grm1	T	A	10: 11,079,866	T225S	possibly damaging	Het
Grm8	C	T	6: 27,285,867	V849I	possibly damaging	Het
Hmcn2	A	G	2: 31,314,590	D59G	probably damaging	Het
Iars	G	A	13: 49,723,077		probably null	Het
Ifi27	C	T	12: 103,437,682	A127V	possibly damaging	Het
Ikbip	A	G	10: 91,096,481	N329S	probably damaging	Het
Ikbke	T	C	1: 131,265,877	T479A	probably benign	Het
Krt12	T	A	11: 99,416,060	N472I	probably damaging	Het
Lmnb2	A	T	10: 80,907,191	L193Q	probably damaging	Het
Lrriq4	T	C	3: 30,650,252	V128A	probably benign	Het
Map4k4	C	A	1: 40,000,757		probably benign	Het
Mtmr7	T	C	8: 40,551,811	T575A	probably benign	Het
Myh13	G	A	11: 67,334,576	A256T	probably benign	Het
Napepld	A	G	5: 21,683,410	Y14H	probably benign	Het
Npr1	T	C	3: 90,459,337	T552A	probably damaging	Het
Nudt15	A	G	14: 73,521,647	F127S	probably benign	Het
Nwd2	T	A	5: 63,808,271	S1733T	probably benign	Het
Olfr1189	A	G	2: 88,592,436	I211V	probably benign	Het
Olfr1257	G	A	2: 89,881,129	G101E	probably damaging	Het
Olfr1348	T	G	7: 6,501,441	I262L	probably benign	Het
Olfr907	A	G	9: 38,499,038	Y123C	probably damaging	Het
Olfr96	T	C	17: 37,225,430	F102L	probably benign	Het
Paqr7	A	T	4: 134,507,098	I89F	probably benign	Het
Pidd1	C	A	7: 141,439,630	V706L	probably benign	Het
Polr3c	A	T	3: 96,713,595	I469N	probably damaging	Het
Ppip5k1	A	G	2: 121,348,547	Y233H	probably damaging	Het
Psmc3	A	G	2: 91,055,995	T166A	possibly damaging	Het
Ptchd3	A	T	11: 121,842,542	I753L	probably benign	Het
Rad21	T	C	15: 51,978,170	K50R	probably damaging	Het
Rad54b	A	G	4: 11,604,989	E479G	possibly damaging	Het
Rfwd3	C	T	8: 111,288,242	R326Q	probably damaging	Het
Rgs20	C	T	1: 4,910,640	R154Q	probably damaging	Het
Sbf1	T	C	15: 89,294,425	D1449G	probably damaging	Het
Sema4g	C	T	19: 45,001,605	R708*	probably null	Het
Sept9	T	C	11: 117,290,428	I18T	probably benign	Het
Serpinb6b	A	G	13: 32,978,058	E280G	probably damaging	Het
Slamf6	T	C	1: 171,942,587		probably benign	Het
Slc6a21	G	A	7: 45,287,734	W554*	probably null	Het
Slco1a4	A	C	6: 141,812,731	I518R	probably benign	Het
Stab1	T	A	14: 31,168,416	Q26L	probably benign	Het
Stox1	A	G	10: 62,667,965	F104L	probably damaging	Het
Suco	T	C	1: 161,834,949	K638E	possibly damaging	Het
Synpo	T	C	18: 60,602,784	K458E	probably damaging	Het
Szt2	A	T	4: 118,372,368	W2820R	unknown	Het
Tmtc1	C	A	6: 148,294,618	G499W	probably damaging	Het
Tonsl	A	C	15: 76,638,066	S242R	probably damaging	Het
Trpc4	G	T	3: 54,194,822	S47I	possibly damaging	Het
Zfp106	G	A	2: 120,520,428	R1581C	probably benign	Het
Zfp27	A	G	7: 29,895,376	L388P	possibly damaging	Het

Other mutations in Dlk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
R0041:Dlk1	UTSW	12	109455513	missense	probably damaging	1.00
R0379:Dlk1	UTSW	12	109455059	unclassified	probably benign
R1250:Dlk1	UTSW	12	109459818	missense	probably damaging	1.00
R1363:Dlk1	UTSW	12	109455504	missense	probably damaging	1.00
R1757:Dlk1	UTSW	12	109459687	missense	probably damaging	1.00
R1772:Dlk1	UTSW	12	109459759	missense	probably damaging	1.00
R2189:Dlk1	UTSW	12	109455049	critical splice donor site	probably null
R2334:Dlk1	UTSW	12	109453688	missense	probably damaging	0.96
R3751:Dlk1	UTSW	12	109460313	missense	probably benign	0.15
R5256:Dlk1	UTSW	12	109459771	missense	probably damaging	1.00
R5268:Dlk1	UTSW	12	109459838	missense	probably benign	0.34
R5356:Dlk1	UTSW	12	109455521	missense	probably damaging	0.99
R5669:Dlk1	UTSW	12	109460038	missense	probably benign	0.04
R5748:Dlk1	UTSW	12	109459972	missense	probably benign	0.00
R5992:Dlk1	UTSW	12	109455581	missense	probably damaging	1.00
R6076:Dlk1	UTSW	12	109459969	missense	probably damaging	0.98
R6539:Dlk1	UTSW	12	109460319	missense	probably benign	0.01
R6638:Dlk1	UTSW	12	109460278	missense	probably damaging	1.00
R7480:Dlk1	UTSW	12	109455614	missense	probably damaging	1.00
R7553:Dlk1	UTSW	12	109454963	missense	unknown
R7602:Dlk1	UTSW	12	109455625	critical splice donor site	probably null
R8531:Dlk1	UTSW	12	109458140	missense	probably null	0.06
R9120:Dlk1	UTSW	12	109458125	missense	probably benign	0.00
R9554:Dlk1	UTSW	12	109454963	missense	unknown
X0020:Dlk1	UTSW	12	109459912	missense	probably damaging	1.00
X0053:Dlk1	UTSW	12	109460137	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