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WormBase Tree Display for Variation: WBVar00274962

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Name Class

WBVar00274962EvidencePaper_evidenceWBPaper00005044
NamePublic_namev33
HGVSgCHROMOSOME_II:g.8124162_8125040del
Sequence_detailsSMapS_parentSequenceC41C4
Flanking_sequencesccgtatcccttccatttattacgttggcttagtttgatgaaaagaatcgtggaaagacctg
Mapping_targetC41C4
Type_of_mutationDeletion
SeqStatusSequenced
Variation_typeAllele
OriginSpeciesCaenorhabditis elegans
StrainWBStrain00033316
LaboratoryRE
StatusLive
AffectsGeneWBGene00002147
TranscriptC41C4.4a.1VEP_consequencesplice_acceptor_variant,splice_donor_variant,coding_sequence_variant,5_prime_UTR_variant,intron_variant
VEP_impactHIGH
cDNA_position?-600
CDS_position?-530
Protein_position?-177
Intron_number2-4/11
Exon_number1-5/12
InteractorWBInteraction000003954
WBInteraction000003955
WBInteraction000051435
WBInteraction000500231
WBInteraction000520460
WBInteraction000520461
WBInteraction000520462
WBInteraction000520656
WBInteraction000536400
WBInteraction000536417
WBInteraction000536420
WBInteraction000536537
WBInteraction000536538
WBInteraction000536539
WBInteraction000536540
WBInteraction000536541
WBInteraction000536542
WBInteraction000536543
WBInteraction000536544
WBInteraction000536545
WBInteraction000536546
WBInteraction000536547
WBInteraction000536548
WBInteraction000536549
WBInteraction000536550
WBInteraction000536551
WBInteraction000536552
WBInteraction000536553
WBInteraction000536554
WBInteraction000536555
WBInteraction000536556
WBInteraction000536557
WBInteraction000536558
WBInteraction000536559
WBInteraction000536560
WBInteraction000536561
WBInteraction000536562
WBInteraction000536563
WBInteraction000536564
WBInteraction000536565
WBInteraction000536566
WBInteraction000536567
WBInteraction000536568
WBInteraction000536569
WBInteraction000536570
WBInteraction000536571
WBInteraction000536572
WBInteraction000536573
WBInteraction000536574
WBInteraction000536575
WBInteraction000536576
WBInteraction000536577
WBInteraction000536578
WBInteraction000536579
WBInteraction000536580
WBInteraction000536581
WBInteraction000536582
WBInteraction000536583
WBInteraction000536584
WBInteraction000536585
WBInteraction000536586
WBInteraction000536587
WBInteraction000536588
WBInteraction000536589
WBInteraction000536590
WBInteraction000536591
WBInteraction000536592
WBInteraction000536593
WBInteraction000536594
WBInteraction000536595
WBInteraction000536596
WBInteraction000536597
WBInteraction000536598
WBInteraction000536599
WBInteraction000536600
WBInteraction000536601
WBInteraction000536602
WBInteraction000536603
WBInteraction000536604
WBInteraction000536605
WBInteraction000536606
WBInteraction000536607
WBInteraction000536608
WBInteraction000536609
WBInteraction000536610
WBInteraction000536611
WBInteraction000536612
WBInteraction000536613
WBInteraction000536614
WBInteraction000536615
WBInteraction000536616
WBInteraction000536617
WBInteraction000536618
WBInteraction000536619
WBInteraction000536620
WBInteraction000536621
WBInteraction000536622
WBInteraction000536623
WBInteraction000536624
WBInteraction000536625
WBInteraction000536626
WBInteraction000536627
WBInteraction000536628
WBInteraction000536629
WBInteraction000536630
WBInteraction000536631
WBInteraction000536632
WBInteraction000536633
WBInteraction000536634
WBInteraction000536635
WBInteraction000536636
WBInteraction000536637
WBInteraction000536638
WBInteraction000536639
WBInteraction000536640
WBInteraction000536641
WBInteraction000536642
WBInteraction000536643
WBInteraction000536644
WBInteraction000536645
WBInteraction000536646
WBInteraction000536647
WBInteraction000536648
WBInteraction000536649
WBInteraction000536650
WBInteraction000536651
WBInteraction000536652
WBInteraction000536653
WBInteraction000536654
WBInteraction000536655
WBInteraction000536656
WBInteraction000536657
WBInteraction000536658
WBInteraction000536659
WBInteraction000536660
WBInteraction000536661
WBInteraction000536757
WBInteraction000536758
WBInteraction000536766
WBInteraction000536819
WBInteraction000537510
IsolationMutagenEMS
GeneticsInterpolated_map_positionII0.694564
DescriptionPhenotypeWBPhenotype:0000031Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Remarkire-1(v33) mutant growth was somewhat slower than observed for wild-type animals.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBPhenotype:0000059Paper_evidenceWBPaper00026830
Curator_confirmedWBPerson712
Remarkire-1(v33); atf-6(ok551) +/ + pek-1(ok275) heterozygotes died, whereas their parents (which had the same genotype) lived, shows that ire-1 has a maternal effectPaper_evidenceWBPaper00026830
Curator_confirmedWBPerson712
MaternalWith_maternal_effectPaper_evidenceWBPaper00026830
Curator_confirmedWBPerson712
Phenotype_assayGenotypeire-1(v33); atf-6(ok551) +/+pek-1(ok275)Paper_evidenceWBPaper00026830
Curator_confirmedWBPerson712
WBPhenotype:0000136Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
RemarkThe ire-1(v33) mutation resulted in increased mRNA levels of genes crt-1, arf-6, F48E8.6, exos-3, and K06A5.8 (Table 1). "Quantitative RT-PCR (qRT-PCR) revealed that the basal expression of 3 of these 10 genes (F48E8.6, exos-3, and K06A5.8) was elevated more than twofold in the ire-1(v33) mutant compared with the wild type, whereas expression of crt-1 was reduced to 44% in the atf-6(tm1153) mutant (Table 1)."Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000137Paper_evidenceWBPaper00035294
WBPaper00036076
WBPaper00041065
Curator_confirmedWBPerson2987
Remark"In the control wild-type N2 worms, expression of ubiquilin and erasin transcripts increased after 6 h of tunicamycin treatment (Fig. 8). However, the induction of both genes was almost completely attenuated in ire-1(v33) mutant worms, and partially attenuated in the atf-6(ok551) and pek-1(ok275) mutants (Fig. 8). Together, these results indicate that in C. elegans, both ubiquilin and erasin genes are chiefly regulated by ire-1."Paper_evidenceWBPaper00035294
Curator_confirmedWBPerson2987
"To determine whether the transcription of rnf-121 is regulated by PEK-1 and the UPR pathway in C . elegans , we performed a real-time PCR analysis of the mutant strains pek-1 ( ok275 ) , ire-1 ( v33 ) , and atf-6 ( ok551 ) , as well as of wild-type worms , treated with the UPR inducers DTT , tunicamycin , and thapsigargin . Although the mRNA levels of hsp-4 were induced upon tunicamycin or DTT treatment and in pek-1 ( ok275 ) and atf-6 ( ok551 ) mutant backgrounds , and abolished in ire-1 ( v33 ) as shown previously ( Shen et al. , 2001 ) , the levels of rnf-121 mRNA were largely unaffected ( Figure 3B ) ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
"... the induction of crt-1 required ire-1 but not atf-6, indicating that crt-1 requires atf-6 for constitutive expression during larval development and requires ire-1/xbp-1 for induction upon acute ER stress, consistent with previous findings (34)."Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00035294
WBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000229Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
Remarkv33 is clearly smaller than the other ER stress transducer strains.Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
WBPhenotype:0000273Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
Remarkire-1 mutant animals had significantly reduced motility in liquid mediaPaper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
WBPhenotype:0000294Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
RemarkThe intestines of mutants remained "dark" due to the lack of lipid droplet hydrolysis.Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
WBPhenotype:0000457Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
Remarkire-1 mutant animals had lower survival rates upon prolonged fasting. Mutant animals displayed substantial paralysis phenotypes upon starvationPaper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
WBPhenotype:0000848Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
RemarkIn the absence of Cry5B, nearly all worms developed to the L4 stage or adulthood for all strains with the exception of ire-1(v33).Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
WBPhenotype:0001013Paper_evidenceWBPaper00045520
Curator_confirmedWBPerson2987
Remark"C. elegans strains lacking xbp-1 and ire-1 displayed enhanced susceptibility to pathogen resulting in complete death of the animals at 16 and 20 h, respectively (Fig. 5)."Paper_evidenceWBPaper00045520
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0042742PATO:0000460Paper_evidenceWBPaper00045520
Curator_confirmedWBPerson2987
WBPhenotype:0001278Paper_evidenceWBPaper00042524
Curator_confirmedWBPerson2987
Remark"We tested whether the cell-nonautonomous activation of the hsp-4p promoter observed in the intestine of rab-3p::xbp-1s animals was also dependent upon an intact UPR-ER. We first expressed rab-3p::xbp-1s in hsp-4p::GFP animals that had an ire-1(v33) mutant background, with an 878 bp deletion extending from 199 bp upstream of the ATG start codon to bp 679 of the ire-1 gene. We found that the ire-1(v33) mutation prevented UPR-ER activation in the intestine of rab-3p::xbp-1s animals, whereas neuronal UPR-ER activation was still significantly upregulated, suggesting that endogenous IRE-1 signaling is required for cell-nonautonomous UPR-ER activation in distal cells (Figures 6A, 6B, S6A, and S6C)."Paper_evidenceWBPaper00042524
Curator_confirmedWBPerson2987
EQ_annotationsAnatomy_termWBbt:0005772PATO:0000460Paper_evidenceWBPaper00042524
Curator_confirmedWBPerson2987
Phenotype_assayGenotyperab-3p::xbp-1s; hsp-4p::GFPPaper_evidenceWBPaper00042524
Curator_confirmedWBPerson2987
WBPhenotype:0001719Paper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
RemarkThe induction of crt-1 was almost abolished in both ire-1(v33) and xbp-1(zc12) mutant wormsPaper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
EQ_annotationsLife_stageWBls:0000023PATO:0000460Paper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
Phenotype_assayTreatmentAnalysis of crt-1 expression under TM (30 ug/ml) stressPaper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
WBPhenotype:0001724Paper_evidenceWBPaper00030877
WBPaper00005044
WBPaper00036076
WBPaper00037064
Curator_confirmedWBPerson2021
WBPerson712
WBPerson2987
Remarkv33 mutants are hypersensitive to TM stressPaper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
On plates with 2 ug/ml of tunicamycin, only 9% of ire-1 animals matured to the L4 stage or older, 60% arrested at or prior to the L3 stage, and 31% were dead. Whereas in the absence of tunicamycin mutants matured to the L4 stage or older within 3 days. N2 animals were resistant to this concentration.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
"The ire-1 ( v33 ) and pek-1 ( ok275 ) mutant strains are more sensitive to tunicamycin than the wild-type ( Figure 3A , bars ; Shen et al . , 2001 ) , whereas atf-6 ( ok551 ) worms are less sensitive to tunicamycin ( Shen et al. , 2005 ) , and in our hands are more resistant than the wild type ( Figure 3A , bars ) ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
"Indeed, in an assay of Tm-induced developmental arrest, both zc14 and tm400 homozygotes and v33 heterozygotes were Tm resistant, whereas v33 homozygotes were Tm hypersensitive, as had been reported previously (Fig. 5C) (48).Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00005044
WBPaper00036076
Curator_confirmedWBPerson712
WBPerson2987
EQ_annotationsLife_stageWBls:0000023PATO:0000460Paper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
WBls:0000035PATO:0000460Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Phenotype_assayTreatmentFor the TM sensitivity assay, gravid adult worms of indicated strain were allowed to lay eggs on plates containing various amount of TM (0, 2, 5, or 10 ug/ml) for 4 h, after which the adults were removed from the plates. The developmental stages of the worms were examined after three daysPaper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
WBPhenotype:0001834Paper_evidenceWBPaper00005044
WBPaper00037064
Curator_confirmedWBPerson712
WBPerson2987
RemarkSplicing of xbp-1 mRNA to remove 23 bases was induced between 30 min - 1 hr after tunicamycin treatment in wild-type L2 larvae. Significantly, this novel mRNA species was not detected in ire-1(v33) mutants.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
"All three ire-1 alleles failed to produce detectable levels of spliced XBP-1 under normal conditions or after an HP incubation (Fig. 6D and E)."Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
WBPhenotype:0001835Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
RemarkIn contrast to wild-type, oxygen consumption rates in ire-1 mutant animals were significantly decreased during fastingPaper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
WBPhenotype:0001838Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
RemarkIn ire-1(v33) mutants, the basal expression of the two hsp genes was similar to that of N2 animals. However, the induction of the hsp-3 gene by DTT or tunicamycin was greatly reduced, and that of hsp-4 was almost abolished.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBMol:00004908Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBPhenotype:0001844Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
RemarkUnlike WT animals, both the number and size of the fat granules inside the intestine remained virtually unchanged in ire-1 mutants after fasting. ire-1 mutant animals fail to hydrolyze fat granules during starvationPaper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
WBPhenotype:0002059Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
RemarkIn the presence of low to moderate levels of the pore forming toxin (PFT) Cry5B, wild-type worms are slightly intoxicated compared to those found on control no-toxin plates, as evidenced by their smaller sizes and paler appearances. However, the mutant worms are more severely intoxicated than wild-type worms as they are relatively smaller and considerably paler compared to their corresponding no toxin controls. NOTE: caution is called for in interpreting the ire-1(v33) data since many of these animals also have significant overt defects, e.g., developmental delays which prevents them from being as well synchronized at the start of the assay compared to the other strains.Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
Affected_byMoleculeWBMol:00005329Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
WBPhenotype:0002422Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Remark"Indeed, in an assay of Tm-induced developmental arrest, both zc14 and tm400 homozygotes and v33 heterozygotes were Tm resistant, whereas v33 homozygotes were Tm hypersensitive, as had been reported previously (Fig. 5C) (48).Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Phenotype_assayGenotypeire-1(v33)/+Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
WBPhenotype:0002423Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
RemarkTunicamycin (Tm) preconditioning in wild type worms leads to increased tolerance to hypoxia. "... three loss-of-function mutant alleles of ire-1 (Fig. 3B), two alleles of atf-6 (Fig. 3D), and an allele of xbp-1 (Fig. 3F) all were defective for Tm preconditioning (Fig. 2D)."Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
"HP (hypoxic preconditioning) consistently provided protection from subsequent harsh hypoxic exposure for wild-type animals (Fig. 4A and B)... Two ire-1 alleles (v33 and ok799) blocked HP (Fig. 4C);"Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Phenotype_not_observedWBPhenotype:0000062Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Remarkire-1(v33) mutants were viable.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBPhenotype:0000114Paper_evidenceWBPaper00036076
WBPaper00041065
Curator_confirmedWBPerson2987
Remark"To determine whether the transcription of rnf-121 is regulated by PEK-1 and the UPR pathway in C . elegans , we performed a real-time PCR analysis of the mutant strains pek-1 ( ok275 ) , ire-1 ( v33 ) , and atf-6 ( ok551 ) , as well as of wild-type worms , treated with the UPR inducers DTT , tunicamycin , and thapsigargin . Although the mRNA levels of hsp-4 were induced upon tunicamycin or DTT treatment and in pek-1 ( ok275 ) and atf-6 ( ok551 ) mutant backgrounds , and abolished in ire-1 ( v33 ) as shown previously ( Shen et al. , 2001 ) , the levels of rnf-121 mRNA were largely unaffected ( Figure 3B ) ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
The ire-1(v33) mutation did not affect mRNA levels of genes 4R79.2, Y39G10AR.8, rpl-1, ZK1098.4, and cpl-1 (Table 1)Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000137Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
Remark"TM (tunicamycin) induction of F48E8.6 did not require ire-1, atf-6, or pek-1, suggesting that its induction did not require any single UPR pathway or that it uses an unconventional UPR pathway (Fig. 1B)."Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000424Paper_evidenceWBPaper00042060
Curator_confirmedWBPerson2987
Remark"Mutants of the two major components of the UPR pathway in C. elegans, ire-1 and xbp-1 (49), were fully sensitive to levamisole and had normal levels of L-AChRs at the NMJ based on immunostaining (Fig. S5 A and B)." (Antibody staining of UNC-38 was normal)Paper_evidenceWBPaper00042060
Curator_confirmedWBPerson2987
WBPhenotype:0000845Paper_evidenceWBPaper00042060
Curator_confirmedWBPerson2987
Remark"Mutants of the two major components of the UPR pathway in C. elegans, ire-1 and xbp-1 (49), were fully sensitive to levamisole and had normal levels of L-AChRs at the NMJ based on immunostaining (Fig. S5 A and B)."Paper_evidenceWBPaper00042060
Curator_confirmedWBPerson2987
WBPhenotype:0001006Paper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
RemarkWhen the worms were fed with bacteria, the pumping rate in ire-1(v33) animals was only slightly decreased (not statistically significant) compared to WT animalsPaper_evidenceWBPaper00033126
Curator_confirmedWBPerson2021
WBPhenotype:0001990Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
WBPhenotype:0002423Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Remark"Mutation of the ER-UPR genes ire-1 and xbp-1 did not suppress Neuro-Nmnat1(gcIs30[Neuro-m-nonN-Nmnat1]) hypoxic survival." (Figure S3b)Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0001666PATO:0000460Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
Phenotype_assayGenotypegcIs30 [Neuro-m-nonN-Nmnat1]Paper_evidenceWBPaper00049307
Curator_confirmedWBPerson2987
ReferenceWBPaper00041065
WBPaper00042060
WBPaper00033126
WBPaper00030877
WBPaper00037064
WBPaper00032255
WBPaper00036076
WBPaper00005044
WBPaper00026830
WBPaper00035294
WBPaper00042524
WBPaper00045520
WBPaper00049307
RemarkA 878 bp deletion extending from 199 bp upstream of the ATG start codon to bp 679 of ire-1 gene.Paper_evidenceWBPaper00005044
MethodDeletion_allele