Incidental Mutation 'R0006:Erbb3'
ID8045
Institutional Source Beutler Lab
Gene Symbol Erbb3
Ensembl Gene ENSMUSG00000018166
Gene Nameerb-b2 receptor tyrosine kinase 3
SynonymsErbb-3, Erbb3r, HER3
MMRRC Submission 041980-MU
Accession Numbers

Ncbi RefSeq: NM_010153.1; MGI:95411

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #R0006 (G1)
Quality Score
Status Validated
Chromosome10
Chromosomal Location128567523-128589652 bp(-) (GRCm38)
Type of Mutationcritical splice donor site (2 bp from exon)
DNA Base Change (assembly) A to G at 128573410 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000080716 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000082059]
Predicted Effect probably null
Transcript: ENSMUST00000082059
SMART Domains Protein: ENSMUSP00000080716
Gene: ENSMUSG00000018166

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Recep_L_domain 55 167 2.4e-31 PFAM
FU 180 220 5.83e0 SMART
FU 223 265 7.63e-10 SMART
Pfam:Recep_L_domain 353 474 7.5e-33 PFAM
FU 490 541 7.82e-7 SMART
FU 546 595 1.34e-5 SMART
FU 607 643 9.24e0 SMART
TyrKc 707 963 7.42e-91 SMART
low complexity region 997 1018 N/A INTRINSIC
low complexity region 1113 1124 N/A INTRINSIC
low complexity region 1135 1148 N/A INTRINSIC
low complexity region 1172 1185 N/A INTRINSIC
low complexity region 1186 1196 N/A INTRINSIC
low complexity region 1201 1213 N/A INTRINSIC
Meta Mutation Damage Score 0.9482 question?
Coding Region Coverage
  • 1x: 77.9%
  • 3x: 66.3%
  • 10x: 36.9%
  • 20x: 17.4%
Validation Efficiency 95% (74/78)
MGI Phenotype Strain: 3513098; 1929072; 1928828; 1929598
Lethality: E10-E14
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations exhibit a lack of Schwann-cell precursors leading to loss of sensory and motor neurons, hypoplasia of the primary sympathetic ganglion chain, cardiac defects, impaired brain development, and embryonic lethality. [provided by MGI curators]
Allele List at MGI

All alleles(27) : Targeted(11) Gene trapped(14) Chemically induced(2)

Other mutations in this stock
Total: 26 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Appl2 A G 10: 83,602,898 F556L probably damaging Het
Atad2b T A 12: 4,942,030 S210T possibly damaging Het
Aurka A G 2: 172,359,753 probably null Het
Chd8 A G 14: 52,235,293 I351T possibly damaging Het
Chid1 T A 7: 141,496,426 probably benign Het
Dnase2b T A 3: 146,582,489 I284F probably damaging Het
Dst C T 1: 34,228,918 T5325I probably benign Het
Fancl A G 11: 26,469,695 N316S possibly damaging Het
Gabrd C A 4: 155,388,601 V72L probably damaging Het
Hephl1 T A 9: 15,076,764 T683S probably benign Het
Jazf1 A G 6: 52,894,086 probably benign Het
Kntc1 T A 5: 123,789,138 S1219T probably benign Het
L3mbtl1 A T 2: 162,964,569 Y460F possibly damaging Het
Map1b C T 13: 99,435,302 V304M probably damaging Het
Msantd4 A G 9: 4,384,099 E140G probably damaging Het
Myo16 A G 8: 10,475,988 K843E probably damaging Het
Rap1gds1 G T 3: 138,983,871 probably null Het
Rsph4a T C 10: 33,909,148 C148R probably damaging Het
Slc7a9 A T 7: 35,470,100 probably benign Het
Sptbn1 A G 11: 30,123,855 S1405P probably damaging Het
Tex35 T C 1: 157,099,744 K154E possibly damaging Het
Tpm3 T A 3: 90,087,661 probably benign Het
Ubr4 T C 4: 139,431,649 F2438L probably benign Het
Wfdc8 T C 2: 164,599,064 D253G probably damaging Het
Zfp451 A T 1: 33,802,780 probably benign Het
Zfp687 A G 3: 95,011,456 I335T probably damaging Het
Other mutations in Erbb3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00659:Erbb3 APN 10 128570983 missense probably damaging 0.99
IGL01482:Erbb3 APN 10 128572929 missense possibly damaging 0.87
IGL01866:Erbb3 APN 10 128569368 makesense probably null
IGL01981:Erbb3 APN 10 128571650 missense probably benign 0.28
IGL02190:Erbb3 APN 10 128571010 splice site probably null
IGL02329:Erbb3 APN 10 128573219 missense probably damaging 1.00
IGL02400:Erbb3 APN 10 128579524 missense probably benign 0.02
IGL02478:Erbb3 APN 10 128571358 nonsense probably null
IGL02502:Erbb3 APN 10 128570284 missense probably benign
IGL02539:Erbb3 APN 10 128584305 splice site probably null
IGL03187:Erbb3 APN 10 128572594 splice site probably benign
I1329:Erbb3 UTSW 10 128583454 missense possibly damaging 0.73
PIT4812001:Erbb3 UTSW 10 128574379 missense possibly damaging 0.67
R0006:Erbb3 UTSW 10 128573410 critical splice donor site probably null
R0078:Erbb3 UTSW 10 128583441 missense probably damaging 1.00
R0366:Erbb3 UTSW 10 128572570 missense possibly damaging 0.77
R0601:Erbb3 UTSW 10 128577012 missense probably benign 0.01
R0621:Erbb3 UTSW 10 128586225 missense probably benign 0.00
R1222:Erbb3 UTSW 10 128571665 missense probably damaging 1.00
R1675:Erbb3 UTSW 10 128571204 missense probably damaging 0.97
R1676:Erbb3 UTSW 10 128583248 missense probably benign 0.08
R1692:Erbb3 UTSW 10 128571725 missense probably benign 0.19
R1875:Erbb3 UTSW 10 128574466 missense possibly damaging 0.71
R2002:Erbb3 UTSW 10 128586225 missense probably benign 0.00
R2219:Erbb3 UTSW 10 128569871 missense probably damaging 0.99
R2328:Erbb3 UTSW 10 128583693 missense probably damaging 1.00
R3840:Erbb3 UTSW 10 128570324 missense probably benign
R4393:Erbb3 UTSW 10 128572770 missense probably damaging 1.00
R4567:Erbb3 UTSW 10 128579075 missense probably damaging 1.00
R4616:Erbb3 UTSW 10 128572770 nonsense probably null
R4766:Erbb3 UTSW 10 128586238 missense possibly damaging 0.76
R4881:Erbb3 UTSW 10 128576947 missense probably benign 0.00
R4974:Erbb3 UTSW 10 128572448 missense probably benign
R5266:Erbb3 UTSW 10 128569636 missense probably damaging 1.00
R5463:Erbb3 UTSW 10 128570079 nonsense probably null
R5481:Erbb3 UTSW 10 128572480 missense probably damaging 0.98
R5997:Erbb3 UTSW 10 128583185 missense probably damaging 1.00
R6370:Erbb3 UTSW 10 128570074 missense possibly damaging 0.90
R7639:Erbb3 UTSW 10 128569847 missense probably damaging 0.99
R7713:Erbb3 UTSW 10 128574449 missense probably benign
Protein Function and Prediction

ERBB3 is a member of the epidermal growth factor receptor (EGFR) family and an activator of the phosphatidylinositol-3-kinase/Akt pathway [reviewed in (1)].  It regulates cell survival and vesicle trafficking and is essential for the generation of precursors of Schwann cells that normally accompany peripheral axons of motor neurons (OMIM: *190151).  ERBB3 expression has been linked to many cancers including breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung [(2); reviewed in (1)]. Neuregulins are among the ligands for ERBB3 and the ligand-receptors are involved in maintenance of cell division, proliferation, differentiation, and migration [reviewed in (1)].

Expression/Localization

ERBB3 mRNA is present from the earliest stages of development and ERBB3 is widely expressed in human adult tissues, consistently detected in brain, spinal cord, liver, prostate, kidney and lung [reviewed in (1)].

Background

Mutations in ERBB3 are linked to Lethal congenital contractural syndrome 2 [LCCS2; OMIM: #607598; (3)], a condition marked by specific neuropathology with degeneration of anterior horn neurons, and extreme skeletal muscle atrophy (4). Most of the infants with LCCS2 died shortly after birth (4). As early as 15 weeks gestation researchers noted fetal akinesia, limb contractures, hydramnios, and distended urinary bladder (4).

 

Erbb3tm1.1Dwt/tm1.1Dwt; MGI:3513098

either: 129S6/SvEvTac-Erbb3tm1.1Dwt or B6.129S6-Erbb3tm1.1Dwt

Homozygous animals die by 3 weeks of age and exhibit partial lethality throughout fetal growth and development (5).

 

Erbb3tm1Cbm/tm1Cbm; MGI:1929072

either: 129P2/OlaHsd or (involves: 129P2/OlaHsd * C57BL/6)

Homozygous animals exhibit complete perinatal lethality, with most animals dying around E11.5 and E13.5.  Pups do not respond to tactile stimuli, have increased neuron apoptosis, neuron degeneration, and respiratory failure (6).

 

Erbb3tm1Gne/tm1Gne; MGI: 1928828

involves: 129S2/SvPas * C57BL/6

Homozygous mice die by E10.5 and exhibit abnormal pancreas morphology, abnormal heart development and morphology, poor circulation, and abnormal brain development (7).

 

Erbb3tm2Cbm/tm2Cbm; MGI:1929598

either: 129P2/OlaHsd or (involves: 129P2/OlaHsd * C57BL/6)

Homozygous animals exhibit complete perinatal lethality, with most animals dying around E11.5 and E13.5.  Pups do not respond to tactile stimuli, have increased neuron apoptosis, neuron degeneration, and respiratory failure (6).

 

Erbb3tm2Cbm/tm2Cbm; MGI:1929598

involves: 129P2/OlaHsd

Adrenergic chromaffin cells are absent in the medulla of homozygous animals.  Furthermore, homozygous animals have abnormal sympathetic system morphology, small superior cervical ganglion, abnormal adrenal gland morphology, abnormal neural crest migration, and a reduction in noradrenaline levels  (8).

References
Posted On2012-11-20
Science WriterAnne Murray