WormMine: Gene WBGene00020490

• WormBase Gene ID: WBGene00020490
• Gene Name: tmc-1
• Sequence Name: T13G4.3
• Brief Description: tmc-1 encodes a multipass transmembrane protein; TMC-1 functions specifically as a sodium-sensitive channel that is required for salt taste chemosensation in the ASH neurons and for high salt avoidance behavior; when expressed in other neurons, TMC-1 is sufficient to generate a salt response in vivo, and when expressed in mammalian cells, TMC-1 generates a predominantly cationic current activated by high extracellular sodium but not other cations or uncharged small molecules; tmc-1 is expressed in sensory neurons, including the ASH, ADF, ASE, ADL, AQR, PQR, URX, and PHA neurons and also at lower frequency in AWC, AFD, and BAG; in ASH, TMC-1 localizes to the cell soma as well as the sensory cilium.
• Organism: Caenorhabditis elegans
• Automated Description: Enables sodium channel activity. Involved in detection of stimulus involved in sensory perception; monoatomic ion transmembrane transport; and sensory perception of chemical stimulus. Located in neuronal cell body; non-motile cilium; and plasma membrane. Expressed in body wall musculature; neurons; and in male. Human ortholog(s) of this gene implicated in autosomal dominant nonsyndromic deafness 36; autosomal recessive nonsyndromic deafness 7; and sensorineural hearing loss. Is an ortholog of human TMC3 (transmembrane channel like 3).
• Biotype: SO:0001217
• Genetic Position: X :-18.4825±
• Length (nt): 14968

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00020490

Genomics

2 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:T13G4.3.2	T13G4.3.2	4493	X: 1162207-1177174
Transcript:T13G4.3.1	T13G4.3.1	4359	X: 1163159-1177172

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:T13G4.3	T13G4.3	3858	X: 1163233-1163313

3 RNAi Result

• WBRNAi00053286
• WBRNAi00017899
• WBRNAi00018692

278 Allele

• gk963725
• WBVar01757194
• WBVar01757195
• WBVar01757196
• WBVar00240945
• otn11598
• WBVar01690045
• WBVar01600431
• WBVar00246244
• WBVar00074735
• WBVar00074734
• WBVar00074733
• WBVar00074732
• WBVar00074737
• WBVar00074736
• WBVar01979175
• WBVar01979174
• WBVar01979173
• WBVar01979172
• WBVar02026612
• WBVar01824097
• gk867596
• gk621716
• gk761274
• gk312745
• gk374959
• gk374958
• gk557371
• gk860251
• gk340220

1 Chromosome

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

1 Chromosome Location

• Feature . Primary Identifier: WBGene00020490
• Start: 1162207
• End: 1177174
• 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_1177175..1180283
• Length (nt): 3109
• Chromosome Location: X: 1177175-1180283
• Organism: Caenorhabditis elegans

143 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 expressed in neuronal cells, by analyzingfluorescence-activated cell sorted (FACS) neurons.	DESeq. False discovry rate (FDR) < 0.1.	WBPaper00048988:neuron_expressed
	Genes significantly enriched (> 2x, FDR < 5%) in a particular cell-type versus a reference sample of all cells at the same stage.	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:A-class-motor-neurons_larva_enriched
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
	mRNAs that showed decreased expression in 1 cell mebryo comparing to in oocyte, according to RNAseq analysis.	Gaussian error propagation. As cutoff for the up-regulated genes authors used log2 fold change > 1 and P < 0.05 and as cutoff for the down-regulated genes authors used log2 fold change < -1 and P < 0.05.	WBPaper00045420:fertilization_downregulated_transcript
	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 that showed significantly increased expression after animals were treated with 50uM Rifampicin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin_upregulated
	Transcripts that showed significantly increased expression after animals were treated with 100uM Rapamycin and 50mM Metformin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Metformin_upregulated
	Transcripts that showed significantly decreased expression at 5-days-post L4 adult N2 hermaphrodites comparing to 1-day-post L4 adult N2 hermaphrodites.	DESeq2, fold change > 2, FDR < 0.05	WBPaper00065835:Day5_vs_Day1_downregulated
	Genes with expression level regulated by genotype (N2 vs CB4856) and age at old adults stage (214 hours at 24 centigrade).	For model 2, authors used 100 permutations to estimate the FDR threshold. Per permutation, genotypes and ages were independently randomly distributed, keeping the among-gene structure intact. Then for each spot (23,232) on the array, model 2 was tested. The obtained P-values were used to estimate a threshold for each of the explanatory factors. Authors also used a genome-wide threshold of -log10 P-value = 2, which resembles an FDR of 0.072 and 0.060 for marker and the interaction age-marker for the developing worms and FDR of 0.050 and 0.065 for marker and age-marker for the aging worms. For the physiological age effect, authors used a log10 P-value = 8 in developing worms (0.012 FDR) and -log10 P-value = 6 (0.032 FDR).	WBPaper00040858:eQTL_age_regulated_aging
	Genes with expression level regulated by genotype (N2 vs CB4856) and age at L3 larva and Late reproduction stage (96 hours at 24 centigrade).	For model 2, authors used 100 permutations to estimate the FDR threshold. Per permutation, genotypes and ages were independently randomly distributed, keeping the among-gene structure intact. Then for each spot (23,232) on the array, model 2 was tested. The obtained P-values were used to estimate a threshold for each of the explanatory factors. Authors also used a genome-wide threshold of -log10 P-value = 2, which resembles an FDR of 0.072 and 0.060 for marker and the interaction age-marker for the developing worms and FDR of 0.050 and 0.065 for marker and age-marker for the aging worms. For the physiological age effect, authors used a log10 P-value = 8 in developing worms (0.012 FDR) and -log10 P-value = 6 (0.032 FDR).	WBPaper00040858:eQTL_age_regulated_developing
	Genes with expression level regulated by genotype (N2 vs CB4856) at old adults stage (214 hours at 24 centigrade).	For model 2, authors used 100 permutations to estimate the FDR threshold. Per permutation, genotypes and ages were independently randomly distributed, keeping the among-gene structure intact. Then for each spot (23,232) on the array, model 2 was tested. The obtained P-values were used to estimate a threshold for each of the explanatory factors. Authors also used a genome-wide threshold of -log10 P-value = 2, which resembles an FDR of 0.072 and 0.060 for marker and the interaction age-marker for the developing worms and FDR of 0.050 and 0.065 for marker and age-marker for the aging worms. For the physiological age effect, authors used a log10 P-value = 8 in developing worms (0.012 FDR) and -log10 P-value = 6 (0.032 FDR).	WBPaper00040858:eQTL_regulated_aging
	Genes with expression level regulated by genotype (N2 vs CB4856) at L3 larva and Late reproduction stage (96 hours at 24 centigrade).	For model 2, authors used 100 permutations to estimate the FDR threshold. Per permutation, genotypes and ages were independently randomly distributed, keeping the among-gene structure intact. Then for each spot (23,232) on the array, model 2 was tested. The obtained P-values were used to estimate a threshold for each of the explanatory factors. Authors also used a genome-wide threshold of -log10 P-value = 2, which resembles an FDR of 0.072 and 0.060 for marker and the interaction age-marker for the developing worms and FDR of 0.050 and 0.065 for marker and age-marker for the aging worms. For the physiological age effect, authors used a log10 P-value = 8 in developing worms (0.012 FDR) and -log10 P-value = 6 (0.032 FDR).	WBPaper00040858:eQTL_regulated_developing
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva daf-16(mu86);glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_daf-16(mu86);glp-1(e2141)
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_glp-1(e2141)
	Transcripts that showed significantly increased expression after four-day-old young adult worms were placed on NGM plates seeded with OP50 in the presence 5% Agaro-oligosaccharides(AGO) for 24 h, comparing to animals grown in the absence of AGO.	Fold change > 2.	WBPaper00064306:Agaro-oligosaccharides_upregulated
	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
	Transcripts that showed significantly increased expression in alg-1(gk214), comparing to in N2.	DESeq2, Fold change > 1.5.	WBPaper00051404:alg-1(gk214)_upregulated
	Transcripts that showed significantly decreased expression in N2 animals exposed to 0.1mM Paraquat from hatching to reaching adult stage.	DESeq2 version 1.22.2, p < 0.05	WBPaper00064716:paraquat_downregulated
	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 xrep-4(lax137).	DESeq2. Genes were selected if their p value < 0.01.	WBPaper00066062:xrep-4(lax137)_upregulated
Reduced humidity (98% relative humidity).	Genes that were down-regulated after one day exposure to reduced humidity (98% relative humidity) according to microarray analysis.	Multiple hypothesis testing with the Benjamini-Hochberg correction was applied on calculated p-values. A change in the expression level was considered to be significant if the adjusted p-value was less than 0.001.	WBPaper00044578:reduced-humidity_downregulated_microarray
	Transcripts that showed significantly increased expression in hpk-1(pk1393) comparing to in N2 at adult day 2.	DESeq 2, fold change > 2, FDR < 0.05.	WBPaper00065581:hpk-1(pk1393)_upregulated
	Transcripts that showed significantly increased expression in hda-1(ne4752[3xFLAG-Degron-HDA-1]) in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:hda-1(ne4752)_upregulated
	Transcripts that showed significantly altered expression at URX, AQR, and PQR neurons in camt-1(ok515) animals comparing to in wild type AX1888-1 strain.	RNA-seq data were mapped using PRAGUI - a Python 3-based pipeline for RNA-seq data analysis.	WBPaper00061902:camt-1(ok515)_regulated_URX-AQR-PQR
	Transcripts that showed significantly increased expression in wdr-23(mac32) embryos from parents fed with E. coliHB101, comparing to N2 embryos parents fed with E. coli HB101.	DESeq2, Fold Change > 2 or < 0.5.	WBPaper00059566:wdr-23(mac32)_upregulated
	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

13 Expression Patterns

• Primary Identifier: Expr2035560
• 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: Expr10754
• Pattern: Expression of tmc-1 was observed in a small number of neurons, including the ASH neurons. Expression was also seen in other sensory neurons, including the ADF, ASE, ADL, AQR, PQR, URX and PHA cells, and at lower frequency, AWC, AFD and BAG.
• Subcellular Localization: The TMC-1::mCherry translational fusion was localized to the cell body as well as the sensory cilia.

• Primary Identifier: Expr12266
• Pattern: In addition to the reported expression pattern (Expr9873, Expr10754), tmc-1 was expressed in body wall muscles, which is promoted by intronic DNA. The 3.6-kb promoter drives the expression in the reported ventral cord and head sensory neurons as-well-as SIBD, SIBV, ALA, AVH head neurons and I1, MC-pharyngeal neurons, and the PHC neurons in the tail.

• Primary Identifier: Expr15539
• Pattern: tmc-1 is expressed in the high-threshold mechanosensor, ALA. Previous research has identified C. elegans tmc-1 gene to be expressed in different tissues such as the body wall muscles and neuronal tissue including sensory neurons, cholinergic ventral cord neurons, and pharyngeal neurons (Chatzigeorgiou et al., 2013; Kratsios et al., 2011; Tang et al., 2020; Zhang et al., 2015). To further investigate the role of TMC-1 in mechanosensory neurons, we firstly generated a new transcriptional reporter line for the endogenous C. elegans tmc-1 promoter (4kb upstream of the start of the tmc-1 gene) driving the red fluorescent protein mKate2 (ljEx1221 [Ptmc-1(4kb)::mKate2]). We confirmed previous results that tmc-1 is expressed in ALA (Zhang et al., 2015) using a reporter strain carrying an ALA neuron marker (ljEx463 [Pida-1::GFP]).

• Primary Identifier: Expr14345
• Pattern: Consistent with previous reports (Chatzigeorgiou et al., 2013; Zhang et al., 2015), we detected the expression of TMC-1 in a wide range of amphid and phasmid neurons as well as body wall muscle cells. Importantly, TMC-1 is also expressed in HSN neurons as indicated by the co-localization of Ptmc-1::mCherry and Pegl-6::GFP, which has been previously reported to label HSN neurons (Ringstad and Horvitz, 2008). However, no TMC-1 expression was detected in vulval muscles using our TMC-1 transcriptional reporter line.

• Primary Identifier: Expr14346
• Pattern: We inserted an in-frame gfp cassette into the endogenous tmc-1 locus using the CRISPR/Cas9 knockin method (Li et al., 2015). Using this approach, we observed TMC-1 expression in vulval muscles as well as several head neurons and body wall muscles.

• Primary Identifier: Expr9873
• Pattern: T13G4.3 is expressed in cholinergic motor neurons of the ventral nerve cord.

• Primary Identifier: Expr16376
• Pattern: tmc-1 is expressed in PHC neurons in both sexes.

• Primary Identifier: Expr1038931
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr1156873
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2017421
• 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: Expr14347
• Subcellular Localization: As the GFP signal is relatively weak in our single copy GFP insertion tmc-1::GFP line, we performed GFP staining to investigate the subcellular localization of TMC-1 protein. Our staining results suggested that a large portion of TMC-1 proteins might be expressed on the plasma membrane.

• Primary Identifier: Expr1017893
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

15 GO Annotation

13 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00020490
• Start: 1162207
• End: 1177174
• Strand: 1

15 Ontology Annotations

2 Regulates Expr Cluster

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly decreased expression in tmc-1(rg1003) comparing to in N2.	DESeq2. The genes with a fold change >= 2 and a false discovery rate (FDR) < 0.05 in a comparison were identified as significant DEGs.	WBPaper00065746:tmc-1(rg1003)_downregulated
	Transcripts that showed significantly increased expression in tmc-1(rg1003) comparing to in N2.	DESeq2. The genes with a fold change >= 2 and a false discovery rate (FDR) < 0.05 in a comparison were identified as significant DEGs.	WBPaper00065746:tmc-1(rg1003)_upregulated

1 Sequence

• Length: 14968

1 Sequence Ontology Term