KLHL38 (8q24.13), C8ORFK36, sydänexpressio , PR intervalliassosiaatio

https://www.ncbi.nlm.nih.gov/gene/340359

Also known as C8ORFK36

Expression Biased expression in heart (RPKM 17.1) and esophagus (RPKM 1.0) See more

Orthologs mouse all

 

1. Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations.  Sano M, et al. Hum Mol Genet, 2014 Dec 15. PMID 25055868Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models.
2. Update on the Kelch-like (KLHL) gene family. Dhanoa BS, et al. Hum Genomics, 2013 May

1. NM_001081675.3 → NP_001075144.2  kelch-like protein 38
   See identical proteins and their annotated locations for NP_001075144.2
   
   
   

   ORIGIN      
           1 mdeesldgll fkdhdfssdl lrqlnslrqs riltdvsica gareipchrn vlassspyfr
          61 amfcssfrek seakvqlkgi dpptldqivs yvytgeahia tdnvlpvmea asmlqfpklf
         121 eacssylqsq lapsnclgmi rlseilscet lkkkareval tsfpevaasa dlkelcalel
         181 rdylgddglc geeekvfeal mvwikhdlqa rkrymqelfk qvrlqyihpa ffhhfianda
         241 llqsspacqi iletakrqmf slcgttvpdc klllhvpprn syqdflillg grkdsqqttr
         301 dvllyskqtg qwqslaklpt rlykasaitl hrsiyvlggm avssgrslvs hnvyifslkl
         361 nqwrlgepml varyshrsta hknfifsigg igegqelmgs merydsicnv wesmasmpvg
         421 vlhpavavkd qrlylfgged imqnpvrliq vyhisrnswf kmetrmiknv capavvlger
         481 ivivggytrr ilaydpqsnk fvkcadmkdr rmhhgatvmg nklyvtggrr lttdcnieds
         541 asfdcydpet dtwtsqgqlp hklfdhaclt lqciprtsgl p
   //

    LxxLL
   Status: VALIDATED

   Conserved Domains (7) summary

   smart00612
   Location:480 → 521

   Kelch; Kelch domain

   PHA03098
   Location:30 → 560

   PHA03098; kelch-like protein; Provisional

   sd00038
   Location:373 → 417

   Kelch; KELCH repeat [structural motif]

   pfam00651
   Location:24 → 128

   BTB; BTB/POZ domain

   pfam01344
   Location:510 → 560

   Kelch_1; Kelch motif

   pfam07707
   Location:136 → 237

   BACK; BTB And C-terminal Kelch

   pfam13964
   Location:281 → 321

   Kelch_6; Kelch motif