WormMine: Gene WBGene00044330

• WormBase Gene ID: WBGene00044330
• Gene Name: alr-1
• Sequence Name: R08B4.2
• Brief Description: alr-1 encodes a homeodomain transcription factor orthologous to aristaless/human Arx; alr-1 regulates the development of sensory neurons in the head and GABAergic motor neurons; ALR-1 affects touch receptor neuron (TRN) fate by acting as a transcriptional activator and is required selectively for TRN gene expression; alr-1 expression in TRNs depends on MEC-3; ALR-1 ensures TRN differentiation by providing a second positive feedback circuit to maintain mec-3 expression; loss of alr-1 produces variable touch sensation; alr-1 increases mec-3 expression by restricting mec-3 expression variability; alr-1 activity is needed throughout larval development; alr-1 is expressed in the ALM, PLM, and AVM TRNs, but not in the nucleus of PVM throughout all larval development.
• Organism: Caenorhabditis elegans
• Automated Description: Enables RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including epidermis morphogenesis; positive regulation of transcription by RNA polymerase II; and sensory perception of touch. Located in nucleus. Expressed in several structures, including anterior hypodermis; neurons; pseudocoelom; socket cell; and somatic nervous system. Used to study non-syndromic X-linked intellectual disability 1. Human ortholog(s) of this gene implicated in several diseases, including X-linked lissencephaly 2; X-linked recessive disease (multiple); and gastrointestinal system cancer (multiple). Is an ortholog of human ALX4 (ALX homeobox 4) and ARX (aristaless related homeobox).
• Biotype: SO:0001217
• Genetic Position: X :2.8601 ±0.00045
• Length (nt): 3750

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00044330

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:R08B4.2.1	R08B4.2.1	1877	X: 11121871-11125620

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:R08B4.2	R08B4.2	1089	X: 11122597-11123021

4 RNAi Result

• WBRNAi00002336
• WBRNAi00051526
• WBRNAi00034737
• WBRNAi00107329

52 Allele

• gk964260
• gk964029
• gk962707
• gk964028
• gk963810
• WBVar01928287
• WBVar01759406
• WBVar01759405
• WBVar01759407
• WBVar01690260
• gk641591
• gk778430
• ok545
• gk402690
• WBVar01602175
• WBVar01602176
• h9050
• WBVar01787024
• gk293474
• gk293473
• gk293472
• gk293471
• gk293470
• gk293469
• gk452641
• gk424906
• gk524924
• gk697393
• gk293475
• gk791141

1 Chromosome

• WormBase ID: X
• Organism: Caenorhabditis elegans
• Length (nt): 17718942

1 Chromosome Location

• Feature . Primary Identifier: WBGene00044330
• Start: 11121871
• End: 11125620
• Strand: -1

4 Data Sets

• WormBaseAcedbConverter
• GO Annotation data set
• C. elegans genomic annotations (GFF3 Gene)
• Panther orthologue and paralogue predictions

1 Downstream Intergenic Region

• WormBase ID: intergenic_region_chrX_11121006..11121870
• Length (nt): 865
• Chromosome Location: X: 11121006-11121870
• Organism: Caenorhabditis elegans

179 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly increased expression in L1 neural cells comparing to in adult neural cells.	DESeq2 (v1.18.1) fold change > 2, P-adj<0.05, using BenjaminiHochberg correction.	WBPaper00060811:L1_vs_adult_upregulated_neural
	Transcripts of coding genes that showed significantly decreased expression in muscle.	DESeq2 (version 1.24.0). Transcripts with a false-discovery rate adjusted p-value less than 0.05 were considered significantly differentially expressed.	WBPaper00062325:muscle_depleted_coding-RNA
	Transcripts expressed in neuronal cells, by analyzingfluorescence-activated cell sorted (FACS) neurons.	DESeq. False discovry rate (FDR) < 0.1.	WBPaper00048988:neuron_expressed
adult vs dauer larva	Transcripts that showed differential expression in adult vs dauer lava in N2 animals at 20C.	N.A.	WBPaper00050488:adult_vs_dauer_regulated_N2_20C
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_Food
	Neuronally enriched transcripts according to a comparison of neuronal nuclei IP samples to total nuclei using isolation of nuclei from tagged specific cell types (INTACT) technology.	DESEQ2, fold change > 2 and FDR < 0.01.	WBPaper00062103:neuron_enriched
Bacteria infection: Enterococcus faecalis	Genes with increased expression after 24 hours of infection by E.faecalis Fold changes shown are pathogen vs OP50.	For RNA-seq and tiling arrays, log2 fold changes between gene expression values of infected versus uninfected nematodes were calculated. For log2 fold changes > 0.00001 the values > 81.25th percentile were defined as up-regulated and for log2 fold changes < -0.00001 the values < 18.75th percentile were defined as down-regulated.	WBPaper00038438:E.faecalis_24hr_upregulated_TilingArray
	Transcripts expressed in the epithelial tissues surrounding the pharynx that includes the arcade and intestinal valve (AIV) cells, according to PAT-Seq analysis using Pbath-15-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:arcade_intestinal-valve_expressed
	Transcripts expressed in body muscle, according to PAT-Seq analysis using Pmyo-3-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:body-muscle_expressed
	Transcripts expressed in GABAergic neuron, according to PAT-Seq analysis using Punc-47-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:GABAergic-neuron_expressed
	Transcripts expressed in hypodermis, according to PAT-Seq analysis using Pdpy-7-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:hypodermis_expressed
	Transcripts expressed in intestine, according to PAT-Seq analysis using Pges-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:intestine_expressed
	Transcripts that showed significantly increased expression in sin-3(tm1276) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:sin-3(tm1276)_upregulated
	Transcripts that showed significantly increased expression in aak-1(tm1944);aak-2(ok524) animals comparing to in N2.	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:aak-1(tm1944);aak-2(ok524)_upregulated
Bacteria infection: Staphylococcus aureus MW2. 4 hours of exposure.	Transcripts that showed significantly increased expression after N2 animals had 4 hours of infection by Staphylococcus aureus (MW2).	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:S.aureus-4h_upregulated_N2
	Transcripts that showed significantly altered expression after 24 hour exposure to stavudine (d4T) starting at L1 lava stage.	DESeq	WBPaper00053302:stavudine_24h_regulated
	Transcripts that showed significantly decreased expression in sin-3(tm1276) comparing to in N2 at early embryo when there were only 3 -5 eggs in the adult.	DESeq2, fold change > 2, adjusted p-value < 0.01	WBPaper00058598:sin-3(tm1276)_downregulated
	Transcripts that showed significantly increased expression in hda-2(ok1479) comparing to in N2 animals.	DESeq2 (version 1.28.1), FDR < 0.01, fold change > 2.	WBPaper00062159:hda-2(ok1479)_upregulated
	Transcripts that showed significantly decreased expression in set-2(tm1630) animals at embryo stage, comparing to in N2 animals.	DESeq2 (v2.1.8.3) was used to determine DE genes and to generate principal component and scatter plots. DE genes with FDR < 0.05 were analysed using g:Profiler with Bonferroni correction.	WBPaper00060014:set-2(tm1630)_downregulated
	Transcripts that showed significantly increased expression in animals lacking P granules by RNAi experiments targeting pgl-1, pgl-3, glh-1 and glh-4, and unc-119-GFP(+), comparing to in control animals, at 2-day post L4 adult hermaphrodite stage.	DESeq2, Benjamini-Hochberg multiple hypothesis corrected p-value < 0.05 and fold change > 2.	WBPaper00050859:upregulated_P-granule(-)GFP(+)_vs_control_day2-adult
	Transcripts that showed significantly increased expression in animals lacking P granules by RNAi experiments targeting pgl-1, pgl-3, glh-1 and glh-4, and unc-119-GFP(-), comparing to in control animals, at 2-day post L4 adult hermaphrodite stage.	DESeq2, Benjamini-Hochberg multiple hypothesis corrected p-value < 0.05 and fold change > 2.	WBPaper00050859:upregulated_P-granule(-)GFP(-)_vs_control_day2-adult
Bacteria infection: Serratia marcescens	Genes with increased expression after 24 hours of infection by S.marcescens Fold changes shown are pathogen vs OP50.	For RNA-seq and tiling arrays, log2 fold changes between gene expression values of infected versus uninfected nematodes were calculated. For log2 fold changes > 0.00001 the values > 81.25th percentile were defined as up-regulated and for log2 fold changes < -0.00001 the values < 18.75th percentile were defined as down-regulated.	WBPaper00038438:S.marcescens_24hr_upregulated_TilingArray
	Genes expressed in N2.	Expressed transcripts were identified on the basis of a Present call in 3 out of 4 N2 experiments as determined by Affymetrix MAS 5.0.	WBPaper00025141:N2_Expressed_Genes
	Embryonic class (E): genes that significantly increase in abundance at some point during embryogenesis.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_E
	Transcripts that showed significantly increased expression in spr-1(ok2144) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:spr-1(ok2144)_upregulated
	Strictly embryonic class (SE): genes that are the subset of embryonic genes that are not also classified as maternal.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_SE
EtBr-exposed(maintained under normal lab light (mostly dark, in incubators) and exposed to EtBr (5ug/mL in agar).) vs UVC-exposed(exposed to 7.5 J/m2 UVC radiation 3 times, 24 h apart (48 h total).) at 3 h after the third UVC dose (51h), which is also 3 h after being placed on food.	Genes differentially expressed under EtBr treatment without UVC exposure vs after UVC exposure but without EtBr treatment at the -3h timepoint (3 h after the third UVC dose (51h), which is also 3 h after being placed on food).	Transcripts were defined as fold-change >1.2, p < 0.05 based on Rosetta Resolver analysis for all pairwise treatment comparisons. The fold-change refers to the second intensity over the first.	WBPaper00041939:EtBr-exposed_vs_UVC-exposed_51h
	Transcripts that showed siginificantly increased expression in nmad-1(ok3133) comparing to in N2 at 25 entigrade.	edgeR, FDR < 0.05, fold change > 2.	WBPaper00056997:nmad-1(ok3133)_upregulated_germline_25C
	Transcripts that showed significantly increased expression in sma-2(rax5) comparing to in N2 at 1-day post-L4 adult hermaphrodite	HTseq-count was used to count reads mapped to each gene and counting data was imported to EdgeR for statistical analysis. Statistical significance was defined by adjusted P value (false discovery rate, FDR) of <0.05.	WBPaper00053184:sma-2(rax5)_upregulated
	Transcripts that showed significantly increased expression in sma-4(rax3) comparing to in N2 at 1-day post-L4 adult hermaphrodite	HTseq-count was used to count reads mapped to each gene and counting data was imported to EdgeR for statistical analysis. Statistical significance was defined by adjusted P value (false discovery rate, FDR) of <0.05.	WBPaper00053184:sma-4(rax3)_upregulated

22 Expression Patterns

• Primary Identifier: Expr2009314
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

• Primary Identifier: Expr15560

• Primary Identifier: Expr3204
• Pattern: GFP in the nuclei and neuronal process of a neuronal cell.
• Subcellular Localization: nuclei and neuronal process

• Primary Identifier: Expr1938
• Remark: Reporter gene fusion type not specified.
• Pattern: R08B4.2 is expressed predominately in neuronal tissue.

• Primary Identifier: Expr11555
• Pattern: Expressed in head and tail neurons, a few cells in the pharynx.

• Primary Identifier: Expr7637
• Remark: Clone: pUL#JRH/AB8
• Pattern: From late embryo to adult can see neurons or muscles on dorsal and ventral sides of very tip of head; also two nerves on lateral sides of anterior bulb of pharynx with processes that extend to head tip; also four to six cells about posterior bulb of pharynx; also dorsal and ventral nerve cords; also two nerve cells in tail. All stages post hatching have expression in two cells on body wall just posterior to the head, and another two cells on the mid ventral body wall that may be coelomocytes.

• Primary Identifier: Expr11069
• Reporter Gene: [ALR-1::GFP] translational fusion and [Palr-1::gfp] transcriptional fusion.
• Pattern: alr-1 is expressed in the ALM, PLM, and AVM touch receptor neurons (TRNs), but not in PVM. alr-1 is expressed in the TRNs at all larval stages.
• Subcellular Localization: An ALR-1::GFP protein fusion was localized exclusively to the nucleus of all of the expressing TRNs throughout all larval development, a result consistent with a role for ALR-1 in transcriptional control.

• Primary Identifier: Expr3525
• Remark: The alr-1p::GFP reporter construct was generated by inserting 1 kb of upstream regulatory sequence into the pPD95.75 vector, which contains the green fluorescent protein (GFP) coding sequence and the 3' untranslated region of unc-54 at the 3' end. This construct was injected into N2 worms at 10 ng/ul along with a PCR product corresponding to 6 kb of overlapping alr-1 upstream regulatory sequence and a dominant Roller marker, pRF4 containing rol-6 (su1006),at 100 ng/ul to generate kuEx146.
• Pattern: Embryonic analysis indicated an early expression pattern just after the 28-cell stage. The strongest expression at this point was seen in descendants of the C linage as well as less prominent expression within a subset of the AB lineage. By the comma stage (-400 cells), GFP expression was apparent in alternating dorsal hypodermal cells before the onset of cell fusions. After the onset of the hypodermal cell fusions, GFP was apparent throughout the hyp7 hypodermal syncytium. At the comma stage, GFP was also strongly expressed in the precursors to the PLM and ALN neurons, the T-cells (precursors to the phasmid socket cells), and the cells that would comprise the hyp4 anterior hypodermal syncytium. These cells were tentatively identified based on cell position and the strong expression seen within the adult structures derived from these cells. A number of GFP-expressing cells within the head region of the embryo remained unidentified. These cells likely include a number of head and pharyngeal neurons, although other cells types are not ruled out. Expression in the larval and adult hermaphrodite was primarily restricted to a subset of neurons and neuronal support cells. The PLM, ALM, and AVM touch neurons and the intrinsic pharyngeal neurons I2 and I6 all showed very strong expression throughout all larval stages and adulthood. The RIS neuron and one other unidentified, unpaired neuronal cell body located in the retrovesicular ganglion occasionally showed faint expression. Strong expression was also seen in the glial-like amphid and phasmid socket cells (AMso and PHso 1 and 2) throughout larval development and adulthood. Strong GFP expression was also observed within the hyp6 and hyp4 hypodermal syncytia, the distal most segments of the intestine and the coelomocytes, the scavenger cells located within the pseudocoelom. Variable GFP expression was also seen in larval and adult worms within the hyp7 hypodermal syncytium. Importantly, GFP expression was not observed in 23 of the 24 GABAergic neurons (the sole exception being the RIS neuron) that have been shown previously to stain with anti-ALR-1 antibodies (See Expr3487). This suggested that the sequences required for ALR-1 expression in these neurons may reside outside of the 6 kb of promoter sequence driving this GFP reporter. Alternatively, GFP expression from this construct may not be readily detectable above background fluorescence in these specific neurons.

• Primary Identifier: Expr3487
• Remark: No staining was observed in alr-1(oy42) mutants.
• Pattern: Staining was first evident in 1.5-fold embryos and although the spatial expression was dynamic, stained neuronal and non-neuronal cells were also observed at later embryonic stages. In larvae and adults, ALR-1 expression was observed in multiple neuronal and non-neuronal cells (including epidermal cells) in the head, neuronal cells in the tail and in the GABAergic DD and VD motoneurons (MNs) in the ventral nerve cord. ALR-1 expression was observed in 24 of 26 GABAergic neurons, including the 13 VD and 6 DD, and the RME L/R, AVL, RIS and DVB neurons throughout postembryonic development.
• Subcellular Localization: Consistent with ALR-1 being a transcription factor, expression was exclusively nuclear in all observed cell types.

• Primary Identifier: Chronogram78
• Remark: Original chronogram file: chronogram.1089.xml
• Reporter Gene: [R08B4.2:gfp] transcriptional fusion.

• Primary Identifier: Expr12558

• Primary Identifier: Expr1200053
• Pattern: Data from the TransgeneOme project

• Primary Identifier: Expr10474
• Pattern: Inferred Expression. EPIC dataset. http://epic.gs.washington.edu/ Large-scale cellular resolution compendium of gene expression dynamics throughout development. This reporter was inferred to be expressing in this cell or one of its embryonic progenitor cells as described below. To generate a compact description of which cells express a particular reporter irrespective of time, the authors defined a metric "peak expression" for each of the 671 terminal ("leaf") cells born during embryogenesis. For each of these cells, the peak expression is the maximal reporter intensity observed in that cell or any of its ancestors; this has the effect of transposing earlier expression forward in time to the terminal set of cells. This metric allows straightforward comparisons of genes' cellular and lineal expression overlap, even when the expression occurs with different timing and despite differences in the precise time point that curation ended in different movies, at the cost of ignoring the temporal dynamics of expression, a topic that requires separate treatment. For simplicity, the authors use the term "expressing cells" to mean the number of leaf cells (of 671) with peak expression greater than background (2000 intensity units) and at least 10% of the maximum expression in that embryo. Quantitative expression data for all cells are located here: ftp://caltech.wormbase.org/pub/wormbase/datasets-published/murray2012/

• Primary Identifier: Expr10473
• Pattern: Inferred Expression. EPIC dataset. http://epic.gs.washington.edu/ Large-scale cellular resolution compendium of gene expression dynamics throughout development. This reporter was inferred to be expressing in this cell or one of its embryonic progenitor cells as described below. To generate a compact description of which cells express a particular reporter irrespective of time, the authors defined a metric "peak expression" for each of the 671 terminal ("leaf") cells born during embryogenesis. For each of these cells, the peak expression is the maximal reporter intensity observed in that cell or any of its ancestors; this has the effect of transposing earlier expression forward in time to the terminal set of cells. This metric allows straightforward comparisons of genes' cellular and lineal expression overlap, even when the expression occurs with different timing and despite differences in the precise time point that curation ended in different movies, at the cost of ignoring the temporal dynamics of expression, a topic that requires separate treatment. For simplicity, the authors use the term "expressing cells" to mean the number of leaf cells (of 671) with peak expression greater than background (2000 intensity units) and at least 10% of the maximum expression in that embryo. Quantitative expression data for all cells are located here: ftp://caltech.wormbase.org/pub/wormbase/datasets-published/murray2012/

• Primary Identifier: Expr13954
• Pattern: A fosmid-based alr-1 translational reporter is expressed in TRNs but not FLP neurons.

• Primary Identifier: Expr9887
• Reporter Gene: [alr-1p::praja::gfp] transcriptional fusion. The alr-1p::praja::gfp plasmid TU#998 was made in two steps: first the ApaI/KpnI praja fragment from mec-18p::praja::gfp (24) replaced the ApaI/KpnI fragment of pPD95.75. Second, the SalI/BamHI alr-1p fragment from TU#905 was inserted in the first construct. --precise ends.
• Pattern: alr-1p::praja::gfp is expressed in the PLM touch receptor neurons at all developmental stages (L1, mid larvae, adult stage).

• Primary Identifier: Chronogram152
• Remark: Original chronogram file: chronogram.1157.xml
• Reporter Gene: [R08B4.2:gfp] transcriptional fusion.

• Primary Identifier: Chronogram899
• Remark: Original chronogram file: chronogram.1945.xml
• Reporter Gene: [R08B4.2:gfp] transcriptional fusion.

• Primary Identifier: Expr1023590
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr2027550
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

• Primary Identifier: Expr1155202
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr1040231
• Pattern: Tiling arrays expression graphs

15 GO Annotation

39 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00044330
• Start: 11121871
• End: 11125620
• Strand: -1

15 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 3750

1 Sequence Ontology Term

• Name: gene

6 Strains

• WBStrain00035327
• WBStrain00031133
• WBStrain00035325
• WBStrain00035326
• WBStrain00031140
• WBStrain00031476

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrX_11125621..11126632
• Length (nt): 1012
• Chromosome Location: X: 11125621-11126632
• Organism: Caenorhabditis elegans