Piezo1 (piezo-type mechanosensitive ion channel component 1) - Rat Genome Database

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Gene: Piezo1 (piezo-type mechanosensitive ion channel component 1) Rattus norvegicus
Analyze
Symbol: Piezo1
Name: piezo-type mechanosensitive ion channel component 1
RGD ID: 1308822
Description: Predicted to enable identical protein binding activity and mechanosensitive monoatomic cation channel activity. Predicted to be involved in several processes, including cellular response to mechanical stimulus; positive regulation of cell-cell adhesion mediated by integrin; and positive regulation of myotube differentiation. Predicted to act upstream of or within monoatomic cation transmembrane transport. Predicted to be located in cuticular plate and stereocilium. Predicted to be active in endoplasmic reticulum and plasma membrane. Human ortholog(s) of this gene implicated in dehydrated hereditary stomatocytosis 1 and hereditary lymphedema. Orthologous to human PIEZO1 (piezo type mechanosensitive ion channel component 1 (Er blood group)); INTERACTS WITH (+)-schisandrin B; acetamide; bisphenol A.
Type: protein-coding
RefSeq Status: PROVISIONAL
Previously known as: Fam38a; family with sequence similarity 38, member A; LOC361430; membrane protein induced by beta-amyloid treatment; Mib
RGD Orthologs
Human
Mouse
Chinchilla
Bonobo
Dog
Squirrel
Pig
Green Monkey
Naked Mole-Rat
Alliance Orthologs
More Info more info ...
Latest Assembly: mRatBN7.2 - mRatBN7.2 Assembly
Position:
Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCr81967,453,120 - 67,515,347 (-)NCBIGRCr8
mRatBN7.21950,544,580 - 50,606,812 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1950,544,582 - 50,606,501 (-)EnsemblmRatBN7.2 Ensembl
UTH_Rnor_SHR_Utx1957,339,473 - 57,401,301 (-)NCBIRnor_SHRUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01958,019,509 - 58,081,421 (-)NCBIRnor_SHRSPUTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01960,238,096 - 60,299,923 (-)NCBIRnor_WKYUTH_Rnor_WKY_Bbb_1.0
Rnor_6.01955,305,494 - 55,367,680 (-)NCBIRnor6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1955,305,496 - 55,367,353 (-)EnsemblRnor6.0rn6Rnor6.0
Rnor_5.01966,014,939 - 66,075,869 (-)NCBIRnor5.0Rnor_5.0rn5Rnor5.0
RGSC_v3.41952,770,967 - 52,834,347 (-)NCBIRGSC3.4RGSC_v3.4rn4RGSC3.4
RGSC_v3.11952,776,154 - 52,852,837 (-)NCBI
Celera1949,784,059 - 49,845,831 (-)NCBICelera
Cytogenetic Map19q12NCBI
JBrowse: View Region in Genome Browser (JBrowse)
Model


Gene-Chemical Interaction Annotations     Click to see Annotation Detail View
Gene Ontology Annotations     Click to see Annotation Detail View

Cellular Component

Molecular Function

References

References - curated
# Reference Title Reference Citation
1. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Gaudet P, etal., Brief Bioinform. 2011 Sep;12(5):449-62. doi: 10.1093/bib/bbr042. Epub 2011 Aug 27.
2. OMIM Disease Annotation Pipeline OMIM Disease Annotation Pipeline
3. ClinVar Automated Import and Annotation Pipeline RGD automated import pipeline for ClinVar variants, variant-to-disease annotations and gene-to-disease annotations
4. Data Import for Chemical-Gene Interactions RGD automated import pipeline for gene-chemical interactions
Additional References at PubMed
PMID:8889548   PMID:16854388   PMID:20016066   PMID:20813920   PMID:22343900   PMID:26390154   PMID:27756599   PMID:29176668   PMID:29261642   PMID:29469092   PMID:29735991   PMID:30004235  
PMID:30948157   PMID:31727906   PMID:33649312   PMID:33839418   PMID:33910401   PMID:34031557   PMID:34359915   PMID:34548087   PMID:34818570   PMID:35219748   PMID:35318857   PMID:35619555  
PMID:35952898   PMID:35988445   PMID:36181398   PMID:36361825   PMID:36461169   PMID:37184045   PMID:37247618   PMID:37420255   PMID:37651768   PMID:38048221   PMID:38235590   PMID:38271270  
PMID:38401846   PMID:39328029  


Genomics

Comparative Map Data
Piezo1
(Rattus norvegicus - Norway rat)
Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCr81967,453,120 - 67,515,347 (-)NCBIGRCr8
mRatBN7.21950,544,580 - 50,606,812 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1950,544,582 - 50,606,501 (-)EnsemblmRatBN7.2 Ensembl
UTH_Rnor_SHR_Utx1957,339,473 - 57,401,301 (-)NCBIRnor_SHRUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01958,019,509 - 58,081,421 (-)NCBIRnor_SHRSPUTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01960,238,096 - 60,299,923 (-)NCBIRnor_WKYUTH_Rnor_WKY_Bbb_1.0
Rnor_6.01955,305,494 - 55,367,680 (-)NCBIRnor6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1955,305,496 - 55,367,353 (-)EnsemblRnor6.0rn6Rnor6.0
Rnor_5.01966,014,939 - 66,075,869 (-)NCBIRnor5.0Rnor_5.0rn5Rnor5.0
RGSC_v3.41952,770,967 - 52,834,347 (-)NCBIRGSC3.4RGSC_v3.4rn4RGSC3.4
RGSC_v3.11952,776,154 - 52,852,837 (-)NCBI
Celera1949,784,059 - 49,845,831 (-)NCBICelera
Cytogenetic Map19q12NCBI
PIEZO1
(Homo sapiens - human)
Human AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCh381688,715,338 - 88,785,220 (-)NCBIGRCh38GRCh38hg38GRCh38
GRCh38.p14 Ensembl1688,715,338 - 88,785,220 (-)EnsemblGRCh38hg38GRCh38
GRCh371688,781,746 - 88,851,628 (-)NCBIGRCh37GRCh37hg19GRCh37
Build 361687,309,247 - 87,351,726 (-)NCBINCBI36Build 36hg18NCBI36
Build 341687,309,255 - 87,330,160NCBI
Celera1673,852,958 - 73,920,009 (-)NCBICelera
Cytogenetic Map16q24.3NCBI
HuRef1674,477,633 - 74,549,500 (-)NCBIHuRef
CHM1_11690,193,016 - 90,262,540 (-)NCBICHM1_1
T2T-CHM13v2.01694,785,806 - 94,856,736 (-)NCBIT2T-CHM13v2.0
Piezo1
(Mus musculus - house mouse)
Mouse AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCm398123,208,437 - 123,278,068 (-)NCBIGRCm39GRCm39mm39
GRCm39 Ensembl8123,208,437 - 123,278,068 (-)EnsemblGRCm39 Ensembl
GRCm388122,481,698 - 122,551,329 (-)NCBIGRCm38GRCm38mm10GRCm38
GRCm38.p6 Ensembl8122,481,698 - 122,551,329 (-)EnsemblGRCm38mm10GRCm38
MGSCv378125,005,598 - 125,075,229 (-)NCBIGRCm37MGSCv37mm9NCBIm37
MGSCv368125,372,380 - 125,437,419 (-)NCBIMGSCv36mm8
Celera8126,710,730 - 126,780,760 (-)NCBICelera
Cytogenetic Map8E1NCBI
cM Map871.31NCBI
Piezo1
(Chinchilla lanigera - long-tailed chinchilla)
Chinchilla AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
ChiLan1.0 EnsemblNW_0049555412,618,438 - 2,643,771 (-)EnsemblChiLan1.0
ChiLan1.0NW_0049555412,618,167 - 2,655,349 (-)NCBIChiLan1.0ChiLan1.0
PIEZO1
(Pan paniscus - bonobo/pygmy chimpanzee)
Bonobo AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
NHGRI_mPanPan1-v21898,488,560 - 98,558,324 (-)NCBINHGRI_mPanPan1-v2
NHGRI_mPanPan116104,400,502 - 104,470,495 (-)NCBINHGRI_mPanPan1
Mhudiblu_PPA_v01669,428,461 - 69,498,454 (-)NCBIMhudiblu_PPA_v0Mhudiblu_PPA_v0panPan3
PanPan1.11689,088,323 - 89,143,463 (-)NCBIpanpan1.1PanPan1.1panPan2
PanPan1.1 Ensembl1689,088,323 - 89,125,068 (-)Ensemblpanpan1.1panPan2
PIEZO1
(Canis lupus familiaris - dog)
Dog AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
CanFam3.1564,584,153 - 64,640,423 (+)NCBICanFam3.1CanFam3.1canFam3CanFam3.1
CanFam3.1 Ensembl564,570,035 - 64,640,375 (+)EnsemblCanFam3.1canFam3CanFam3.1
Dog10K_Boxer_Tasha564,595,638 - 64,651,743 (+)NCBIDog10K_Boxer_Tasha
ROS_Cfam_1.0564,804,439 - 64,860,493 (+)NCBIROS_Cfam_1.0
ROS_Cfam_1.0 Ensembl564,804,155 - 64,860,483 (+)EnsemblROS_Cfam_1.0 Ensembl
UMICH_Zoey_3.1564,830,683 - 64,886,668 (+)NCBIUMICH_Zoey_3.1
UNSW_CanFamBas_1.0564,662,209 - 64,718,234 (+)NCBIUNSW_CanFamBas_1.0
UU_Cfam_GSD_1.0565,068,355 - 65,124,410 (+)NCBIUU_Cfam_GSD_1.0
Piezo1
(Ictidomys tridecemlineatus - thirteen-lined ground squirrel)
Squirrel AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
HiC_Itri_2NW_02440934925,178,700 - 25,226,974 (+)NCBIHiC_Itri_2
SpeTri2.0 EnsemblNW_004936641932,577 - 980,233 (+)EnsemblSpeTri2.0SpeTri2.0 Ensembl
SpeTri2.0NW_004936641932,291 - 980,440 (+)NCBISpeTri2.0SpeTri2.0SpeTri2.0
PIEZO1
(Sus scrofa - pig)
Pig AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
Sscrofa11.1 Ensembl6914,709 - 967,111 (+)EnsemblSscrofa11.1susScr11Sscrofa11.1
Sscrofa11.16914,480 - 967,113 (+)NCBISscrofa11.1Sscrofa11.1susScr11Sscrofa11.1
Sscrofa10.2654,610,402 - 54,612,349 (-)NCBISscrofa10.2Sscrofa10.2susScr3
PIEZO1
(Chlorocebus sabaeus - green monkey)
Green Monkey AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
ChlSab1.1574,100,675 - 74,167,194 (-)NCBIChlSab1.1ChlSab1.1chlSab2
ChlSab1.1 Ensembl574,100,929 - 74,134,167 (-)EnsemblChlSab1.1ChlSab1.1 EnsemblchlSab2
Vero_WHO_p1.0NW_0236660471,512,166 - 1,579,247 (+)NCBIVero_WHO_p1.0Vero_WHO_p1.0
Piezo1
(Heterocephalus glaber - naked mole-rat)
Naked Mole-Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
HetGla_female_1.0 EnsemblNW_004624746821,726 - 871,481 (+)EnsemblHetGla_female_1.0HetGla_female_1.0 EnsemblhetGla2
HetGla 1.0NW_004624746821,651 - 871,481 (+)NCBIHetGla_female_1.0HetGla 1.0hetGla2

Variants

.
Variants in Piezo1
273 total Variants
miRNA Target Status

Predicted Target Of
Summary Value
Count of predictions:89
Count of miRNA genes:72
Interacting mature miRNAs:83
Transcripts:ENSRNOT00000058332
Prediction methods:Miranda, Rnahybrid, Targetscan
Result types:miRGate_prediction

The detailed report is available here: Full Report CSV TAB Printer

miRNA Target Status data imported from miRGate (http://mirgate.bioinfo.cnio.es/).
For more information about miRGate, see PMID:25858286 or access the full paper here.


QTLs in Region (mRatBN7.2)
The following QTLs overlap with this region.    Full Report CSV TAB Printer Gviewer
RGD IDSymbolNameLODP ValueTraitSub TraitChrStartStopSpecies
2313395Anxrr26Anxiety related response QTL 26aggression-related behavior trait (VT:0015014)tameness/aggressiveness composite score (CMO:0002136)194997648153225766Rat
1578764Stresp19Stress response QTL 193.60.001blood renin amount (VT:0003349)plasma renin activity level (CMO:0000116)191563020157337602Rat
61350Bp32Blood pressure QTL 320.012arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)192048357557337602Rat
5135224Leukc1Leukocyte quantity QTL 1eosinophil quantity (VT:0002602)blood eosinophil count (CMO:0000033)194434021455283277Rat
724546Kidm3Kidney mass QTL 33.1kidney mass (VT:0002707)calculated kidney weight (CMO:0000160)192932249057337602Rat
7411549Bw130Body weight QTL 13050.001body mass (VT:0001259)body weight gain (CMO:0000420)191545586057337602Rat
1358200Insglur2Insulin/glucose ratio QTL 24.1blood glucose amount (VT:0000188)serum glucose level (CMO:0000543)193383821455283146Rat
724566Uae12Urinary albumin excretion QTL 125urine albumin amount (VT:0002871)urine albumin level (CMO:0000130)19218792756457239Rat
1331737Uae29Urinary albumin excretion QTL 295.5urine albumin amount (VT:0002871)urine albumin level (CMO:0000130)19409615555283277Rat
2298478Eau8Experimental allergic uveoretinitis QTL 80.0163uvea integrity trait (VT:0010551)experimental autoimmune uveitis score (CMO:0001504)191715443357337602Rat

Markers in Region
RH131577  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21950,544,232 - 50,544,563 (+)MAPPERmRatBN7.2
Rnor_6.01955,305,147 - 55,305,477NCBIRnor6.0
Rnor_5.01966,014,592 - 66,014,922UniSTSRnor5.0
RGSC_v3.41952,770,620 - 52,770,950UniSTSRGSC3.4
Celera1949,783,712 - 49,784,042UniSTS
RH 3.4 Map19701.3UniSTS
Cytogenetic Map19q12UniSTS
RH141716  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21950,544,757 - 50,544,940 (+)MAPPERmRatBN7.2
Rnor_6.01955,305,672 - 55,305,854NCBIRnor6.0
Rnor_5.01966,015,117 - 66,015,299UniSTSRnor5.0
RGSC_v3.41952,771,145 - 52,771,327UniSTSRGSC3.4
Celera1949,784,237 - 49,784,419UniSTS
RH 3.4 Map19698.5UniSTS
Cytogenetic Map19q12UniSTS
MARC_12079-12080:1004624307:1  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21950,554,920 - 50,555,531 (+)MAPPERmRatBN7.2
Rnor_6.01955,315,834 - 55,316,444NCBIRnor6.0
Rnor_5.01966,025,279 - 66,025,889UniSTSRnor5.0
RGSC_v3.41952,781,307 - 52,781,917UniSTSRGSC3.4
Celera1949,794,236 - 49,794,846UniSTS
Cytogenetic Map19q12UniSTS


Expression

RNA-SEQ Expression

alimentary part of gastrointestinal system
appendage
circulatory system
ectoderm
endocrine system
endoderm
exocrine system
hemolymphoid system
hepatobiliary system
integumental system
mesenchyme
mesoderm
nervous system
renal system
reproductive system
respiratory system
9 11 49 113 91 90 59 25 59 6 218 97 93 45 60 31

Sequence


Ensembl Acc Id: ENSRNOT00000091139   ⟹   ENSRNOP00000069995
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 Ensembl1950,544,582 - 50,606,501 (-)Ensembl
Rnor_6.0 Ensembl1955,305,496 - 55,367,353 (-)Ensembl
Ensembl Acc Id: ENSRNOT00000105150   ⟹   ENSRNOP00000077382
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 Ensembl1950,544,582 - 50,606,501 (-)Ensembl
RefSeq Acc Id: NM_001077200   ⟹   NP_001070668
RefSeq Status: PROVISIONAL
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81967,453,120 - 67,515,037 (-)NCBI
mRatBN7.21950,544,580 - 50,606,501 (-)NCBI
Rnor_6.01955,305,494 - 55,367,353 (-)NCBI
Rnor_5.01966,014,939 - 66,075,869 (-)NCBI
RGSC_v3.41952,770,967 - 52,834,347 (-)RGD
Celera1949,784,059 - 49,845,831 (-)RGD
Sequence:
RefSeq Acc Id: XM_008772626   ⟹   XP_008770848
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81967,453,138 - 67,515,334 (-)NCBI
mRatBN7.21950,544,580 - 50,606,803 (-)NCBI
Rnor_6.01955,305,494 - 55,367,680 (-)NCBI
Sequence:
RefSeq Acc Id: XM_008772627   ⟹   XP_008770849
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81967,453,138 - 67,515,334 (-)NCBI
mRatBN7.21950,544,580 - 50,606,803 (-)NCBI
Rnor_6.01955,305,494 - 55,367,680 (-)NCBI
Sequence:
RefSeq Acc Id: XM_017601325   ⟹   XP_017456814
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81967,453,138 - 67,479,525 (-)NCBI
mRatBN7.21950,544,580 - 50,570,977 (-)NCBI
Rnor_6.01955,305,494 - 55,360,135 (-)NCBI
Sequence:
RefSeq Acc Id: XM_039097875   ⟹   XP_038953803
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81967,453,138 - 67,482,250 (-)NCBI
mRatBN7.21950,544,580 - 50,573,720 (-)NCBI
RefSeq Acc Id: XM_063278152   ⟹   XP_063134222
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81967,458,302 - 67,515,347 (-)NCBI
RefSeq Acc Id: NP_001070668   ⟸   NM_001077200
- UniProtKB: Q0KL00 (UniProtKB/Swiss-Prot)
- Sequence:
RefSeq Acc Id: XP_008770849   ⟸   XM_008772627
- Peptide Label: isoform X2
- UniProtKB: A0A8I5Y135 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: XP_008770848   ⟸   XM_008772626
- Peptide Label: isoform X1
- UniProtKB: A0A0G2JWS3 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: XP_017456814   ⟸   XM_017601325
- Peptide Label: isoform X3
- Sequence:
Ensembl Acc Id: ENSRNOP00000069995   ⟸   ENSRNOT00000091139
RefSeq Acc Id: XP_038953803   ⟸   XM_039097875
- Peptide Label: isoform X3
Ensembl Acc Id: ENSRNOP00000077382   ⟸   ENSRNOT00000105150
RefSeq Acc Id: XP_063134222   ⟸   XM_063278152
- Peptide Label: isoform X4
Protein Domains
PIEZO   Piezo non-specific cation channel R-Ras-binding

Protein Structures
Name Modeler Protein Id AA Range Protein Structure
AF-Q0KL00-F1-model_v2 AlphaFold Q0KL00 1-2535 view protein structure

Transcriptome

eQTL   View at Phenogen
WGCNA   View at Phenogen
Tissue/Strain Expression   View at Phenogen

Promoters
RGD ID:13701209
Promoter ID:EPDNEW_R11733
Type:single initiation site
Name:Piezo1_1
Description:piezo-type mechanosensitive ion channel component 1
SO ACC ID:SO:0000170
Source:EPDNEW (Eukaryotic Promoter Database, http://epd.vital-it.ch/)
Experiment Methods:Single-end sequencing.
Position:
Rat AssemblyChrPosition (strand)Source
Rnor_6.01955,367,347 - 55,367,407EPDNEW

Additional Information

Database Acc Id Source(s)
AGR Gene RGD:1308822 AgrOrtholog
BioCyc Gene G2FUF-5393 BioCyc
Ensembl Genes ENSRNOG00000056786 Ensembl, UniProtKB/TrEMBL
Ensembl Transcript ENSRNOT00000091139.2 UniProtKB/TrEMBL
  ENSRNOT00000105150.1 UniProtKB/TrEMBL
InterPro Piezo UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  Piezo_dom UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  Piezo_RRas-bd_dom UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
KEGG Report rno:361430 UniProtKB/Swiss-Prot
NCBI Gene 361430 ENTREZGENE
PANTHER PIEZO-TYPE MECHANOSENSITIVE ION CHANNEL COMPONENT UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  PIEZO-TYPE MECHANOSENSITIVE ION CHANNEL HOMOLOG UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
Pfam PIEZO UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  Piezo_RRas_bdg UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
PhenoGen Piezo1 PhenoGen
RatGTEx ENSRNOG00000056786 RatGTEx
UniProt A0A0G2JWS3 ENTREZGENE, UniProtKB/TrEMBL
  A0A8I5Y135 ENTREZGENE, UniProtKB/TrEMBL
  PIEZ1_RAT UniProtKB/Swiss-Prot, ENTREZGENE


Nomenclature History
Date Current Symbol Current Name Previous Symbol Previous Name Description Reference Status
2012-07-16 Piezo1  piezo-type mechanosensitive ion channel component 1  Fam38a  family with sequence similarity 38, member A  Nomenclature updated to reflect human and mouse nomenclature 1299863 APPROVED
2008-04-30 Fam38a  family with sequence similarity 38, member A   Fam38a_predicted  family with sequence similarity 38, member A (predicted)  'predicted' is removed 2292626 APPROVED
2005-01-12 Fam38a_predicted  family with sequence similarity 38, member A (predicted)      Symbol and Name status set to approved 70820 APPROVED