Mutagenetix > Incidental Mutation

Incidental Mutation 'I2289:Heg1'

595

Institutional Source

Beutler Lab

Gene Symbol

Heg1

Ensembl Gene

ENSMUSG00000075254

Gene Name

heart development protein with EGF-like domains 1

Synonyms

9530025L16Rik, 4632417D23Rik, LOC268884, 5530401I02Rik

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.260) question?

Stock #

I2289 (G3) of strain 633

Quality Score

Status

Validated

Chromosome

Chromosomal Location

33504754-33591946 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 33583829 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 1212 (I1212T)

Ref Sequence

ENSEMBL: ENSMUSP00000155944 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000126532] [ENSMUST00000128105] [ENSMUST00000152782] [ENSMUST00000232568]

AlphaFold

E9Q7X6

Predicted Effect

probably damaging
Transcript: ENSMUST00000126532
AA Change: I1236T

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

SMART Domains

Protein: ENSMUSP00000119790
Gene: ENSMUSG00000075254
AA Change: I1236T

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
low complexity region	53	66	N/A	INTRINSIC
low complexity region	68	80	N/A	INTRINSIC
low complexity region	175	190	N/A	INTRINSIC
low complexity region	265	282	N/A	INTRINSIC
low complexity region	471	480	N/A	INTRINSIC
low complexity region	486	502	N/A	INTRINSIC
low complexity region	556	575	N/A	INTRINSIC
low complexity region	637	682	N/A	INTRINSIC
low complexity region	868	888	N/A	INTRINSIC
EGF	944	979	4e-5	SMART
EGF_CA	981	1019	1.01e-10	SMART
EGF_like	1139	1187	6.81e1	SMART
transmembrane domain	1204	1226	N/A	INTRINSIC
PDB:4HDQ\|C	1312	1337	2e-10	PDB

Predicted Effect

possibly damaging
Transcript: ENSMUST00000128105
AA Change: I37T

PolyPhen 2 Score 0.462 (Sensitivity: 0.89; Specificity: 0.90)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146518

Predicted Effect

probably damaging
Transcript: ENSMUST00000152782
AA Change: I981T

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

SMART Domains

Protein: ENSMUSP00000123686
Gene: ENSMUSG00000075254
AA Change: I981T

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
low complexity region	53	66	N/A	INTRINSIC
low complexity region	68	104	N/A	INTRINSIC
low complexity region	170	183	N/A	INTRINSIC
low complexity region	185	202	N/A	INTRINSIC
low complexity region	301	320	N/A	INTRINSIC
low complexity region	382	427	N/A	INTRINSIC
low complexity region	613	633	N/A	INTRINSIC
EGF	689	724	4e-5	SMART
EGF_CA	726	764	1.01e-10	SMART
EGF_like	884	932	6.81e1	SMART
transmembrane domain	949	971	N/A	INTRINSIC
PDB:4HDQ\|C	1057	1082	1e-10	PDB

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000152832

Predicted Effect

probably damaging
Transcript: ENSMUST00000232568
AA Change: I1212T

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

Meta Mutation Damage Score

0.5075

Coding Region Coverage

1x: 87.8%
3x: 75.8%

Het Detection Efficiency

55.8%

Validation Efficiency

88% (46/52)

MGI Phenotype

PHENOTYPE: Mice homozygous for a knock-out allele exhibit impaired integrity of the heart, blood vessels and lymphatic vessels, resulting in hemopericardium, lung hemorrhage, lymphangiectasis, and chylous ascites, as well as embryonic and postnatal lethality. [provided by MGI curators]

Allele List at MGI

All alleles(6) : Targeted, knock-out(3) Gene trapped(3)

Other mutations in this stock

Total: 21 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts12	T	A	15: 11,071,894 (GRCm39)	L146Q	probably benign	Homo
Adgrv1	A	G	13: 81,585,643 (GRCm39)	L4607P	probably damaging	Het
Amelx	A	G	X: 167,961,009 (GRCm39)		probably null	Homo
Ankfy1	A	G	11: 72,621,311 (GRCm39)	K199R	probably benign	Het
Arfgef1	T	C	1: 10,243,478 (GRCm39)	K1024E	probably damaging	Het
Bank1	T	A	3: 135,760,179 (GRCm39)	D782V	probably damaging	Homo
Csmd1	A	T	8: 15,962,381 (GRCm39)	I3271K	probably benign	Homo
Fat1	A	G	8: 45,478,033 (GRCm39)	I2360V	probably benign	Homo
Gldc	G	A	19: 30,124,576 (GRCm39)	R241*	probably null	Het
Golgb1	A	G	16: 36,718,904 (GRCm39)	H270R	probably benign	Het
Hes1	T	A	16: 29,884,699 (GRCm39)	S53R	probably damaging	Het
Ibsp	G	A	5: 104,450,353 (GRCm39)	R57Q	possibly damaging	Homo
Lrp1b	A	T	2: 41,012,944 (GRCm39)	I2001K	probably damaging	Het
Nf1	G	A	11: 79,438,602 (GRCm39)	R2181H	probably damaging	Het
Nrcam	C	A	12: 44,611,098 (GRCm39)	H567Q	probably benign	Homo
Or51a10	T	C	7: 103,698,961 (GRCm39)	Y200C	probably damaging	Homo
Or5bw2	A	T	7: 6,573,818 (GRCm39)	Y276F	probably damaging	Het
Rraga	T	C	4: 86,494,522 (GRCm39)	F123L	probably damaging	Het
Spam1	A	G	6: 24,796,477 (GRCm39)	I143V	probably benign	Het
Synj2	A	G	17: 6,072,542 (GRCm39)		probably benign	Homo
T	A	T	17: 8,657,474 (GRCm39)	T112S	probably benign	Homo

Other mutations in Heg1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00966:Heg1	APN	16	33,530,977 (GRCm39)	missense	probably damaging	0.98
IGL01133:Heg1	APN	16	33,547,657 (GRCm39)	missense	probably benign	0.01
IGL01410:Heg1	APN	16	33,545,936 (GRCm39)	missense	possibly damaging	0.95
IGL01561:Heg1	APN	16	33,587,038 (GRCm39)	missense	probably benign	0.27
IGL02449:Heg1	APN	16	33,559,095 (GRCm39)	critical splice donor site	probably null
IGL02523:Heg1	APN	16	33,558,992 (GRCm39)	missense	probably damaging	1.00
IGL02794:Heg1	APN	16	33,546,992 (GRCm39)	missense	probably damaging	0.99
IGL03240:Heg1	APN	16	33,547,783 (GRCm39)	missense	probably benign	0.02
cardiac	UTSW	16	33,583,961 (GRCm39)	missense	probably damaging	1.00
dictator	UTSW	16	33,527,367 (GRCm39)	missense	probably benign	0.26
hegemon	UTSW	16	33,581,173 (GRCm39)	missense	probably damaging	1.00
oedema	UTSW	16	33,558,961 (GRCm39)	missense	probably benign	0.03
wittgenstein	UTSW	16	33,541,100 (GRCm39)	nonsense	probably null
R0089:Heg1	UTSW	16	33,583,985 (GRCm39)	missense	probably damaging	1.00
R0116:Heg1	UTSW	16	33,556,028 (GRCm39)	splice site	probably benign
R0514:Heg1	UTSW	16	33,547,126 (GRCm39)	missense	possibly damaging	0.86
R0589:Heg1	UTSW	16	33,552,077 (GRCm39)	missense	probably damaging	1.00
R0942:Heg1	UTSW	16	33,581,173 (GRCm39)	missense	probably damaging	1.00
R1084:Heg1	UTSW	16	33,527,367 (GRCm39)	missense	probably benign	0.26
R1109:Heg1	UTSW	16	33,583,961 (GRCm39)	missense	probably damaging	1.00
R1375:Heg1	UTSW	16	33,547,679 (GRCm39)	missense	possibly damaging	0.60
R1375:Heg1	UTSW	16	33,547,246 (GRCm39)	missense	possibly damaging	0.75
R1550:Heg1	UTSW	16	33,555,923 (GRCm39)	missense	probably damaging	1.00
R1720:Heg1	UTSW	16	33,527,549 (GRCm39)	missense	probably benign	0.44
R1739:Heg1	UTSW	16	33,558,953 (GRCm39)	missense	possibly damaging	0.94
R2068:Heg1	UTSW	16	33,547,960 (GRCm39)	missense	probably benign	0.14
R2397:Heg1	UTSW	16	33,562,849 (GRCm39)	missense	probably damaging	0.99
R4353:Heg1	UTSW	16	33,530,847 (GRCm39)	missense	probably benign	0.41
R4419:Heg1	UTSW	16	33,547,805 (GRCm39)	missense	probably benign	0.23
R4420:Heg1	UTSW	16	33,547,805 (GRCm39)	missense	probably benign	0.23
R4779:Heg1	UTSW	16	33,540,142 (GRCm39)	missense	probably benign	0.41
R5066:Heg1	UTSW	16	33,559,041 (GRCm39)	missense	probably benign	0.41
R5227:Heg1	UTSW	16	33,583,961 (GRCm39)	missense	probably damaging	1.00
R5494:Heg1	UTSW	16	33,545,804 (GRCm39)	missense	probably benign	0.44
R5645:Heg1	UTSW	16	33,527,333 (GRCm39)	missense	probably benign
R5708:Heg1	UTSW	16	33,562,774 (GRCm39)	missense	probably damaging	0.99
R5934:Heg1	UTSW	16	33,547,289 (GRCm39)	missense	probably damaging	1.00
R6074:Heg1	UTSW	16	33,547,573 (GRCm39)	missense	possibly damaging	0.49
R6374:Heg1	UTSW	16	33,547,499 (GRCm39)	missense	possibly damaging	0.86
R6398:Heg1	UTSW	16	33,587,145 (GRCm39)	missense	probably damaging	0.99
R6774:Heg1	UTSW	16	33,558,638 (GRCm39)	missense	probably damaging	1.00
R6843:Heg1	UTSW	16	33,539,896 (GRCm39)	missense	probably benign	0.41
R7091:Heg1	UTSW	16	33,547,090 (GRCm39)	missense	probably benign	0.01
R7183:Heg1	UTSW	16	33,558,920 (GRCm39)	splice site	probably null
R7186:Heg1	UTSW	16	33,552,034 (GRCm39)	missense	probably damaging	1.00
R7294:Heg1	UTSW	16	33,546,859 (GRCm39)	missense	probably damaging	0.99
R7304:Heg1	UTSW	16	33,581,160 (GRCm39)	missense	possibly damaging	0.52
R7405:Heg1	UTSW	16	33,583,819 (GRCm39)	missense	possibly damaging	0.66
R7614:Heg1	UTSW	16	33,547,733 (GRCm39)	missense	probably benign
R7638:Heg1	UTSW	16	33,547,867 (GRCm39)	missense	probably damaging	1.00
R7880:Heg1	UTSW	16	33,539,879 (GRCm39)	missense	possibly damaging	0.93
R7942:Heg1	UTSW	16	33,571,570 (GRCm39)	missense	probably damaging	1.00
R7977:Heg1	UTSW	16	33,541,100 (GRCm39)	nonsense	probably null
R7984:Heg1	UTSW	16	33,583,945 (GRCm39)	missense	possibly damaging	0.83
R7987:Heg1	UTSW	16	33,541,100 (GRCm39)	nonsense	probably null
R8023:Heg1	UTSW	16	33,550,895 (GRCm39)	missense	possibly damaging	0.61
R8312:Heg1	UTSW	16	33,547,045 (GRCm39)	missense	probably benign	0.02
R8745:Heg1	UTSW	16	33,555,986 (GRCm39)	missense	probably benign	0.00
R8843:Heg1	UTSW	16	33,570,863 (GRCm39)	missense	probably null	1.00
R8911:Heg1	UTSW	16	33,558,627 (GRCm39)	nonsense	probably null
R9036:Heg1	UTSW	16	33,527,339 (GRCm39)	missense	probably benign
R9149:Heg1	UTSW	16	33,558,961 (GRCm39)	missense	probably benign	0.03
R9351:Heg1	UTSW	16	33,545,867 (GRCm39)	missense	probably benign	0.41
R9682:Heg1	UTSW	16	33,541,298 (GRCm39)	missense	probably benign	0.26
X0066:Heg1	UTSW	16	33,547,786 (GRCm39)	missense	probably benign	0.16
Z1177:Heg1	UTSW	16	33,541,057 (GRCm39)	missense	probably damaging	0.99

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 3088 of the Heg1 transcript in exon 16 of 17 exons using Genbank record NM_175256.5. Multiple transcripts of the Heg1 gene are displayed on Ensembl and Vega. The mutated nucleotide causes an isoleucine to threonine substitution at amino acid 981 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method.

Protein Function and Prediction

The Heg1 gene encodes a 1082 amino acid novel type I transmembrane receptor. Homozygous null mice display partial penetrance of prenatal and postnatal lethality with abnormal heart development, hemorrhages, and leaky lymphatic vessels. The HEG1 protein contains three calcium-binding EGF-like domains in its extracellular region (residues 689-724, 726-764, and 884-932) using SMART analysis.

The I981T alteration occurs in the cytoplasmic region of the protein.

Posted On

2011-03-07