PhenoModifier-Gene Detail

Gene "ATP12A"

Found 1 record

Gene information

Gene symbol:

ATP12A

See related:

Ensembl: ENSG00000075673, Gene ID: 479

Additive variants :

Detected

Genetic interaction partners

Confidence	Stringent (ε>0.16 or ε<-0.12)	Intermediate (-0.16≤ε≤-0.08 or 0.08≤ε≤0.16)	Lenient (\|ε\|<0.08)
Positive interactions	DMXL1 MAP3K2 ZDHHC4 TOP1 RCOR1 NF1 MAST2 INPP5E SUB1 TGIF2 ARL1 SLC11A2 SUCLG1 CS RAB6B USP41 RPL37A ARL13B EEF1G RBBP5 RACK1 PDCD6IP ASH1L PPM1G DOT1L ELOF1 AIRE SRPK2 GET4 ALG6 XPR1 IPO8 LETM1 CHPT1 TEAD4 WDR6 DNM1L RPS24 ZMPSTE24 WDR59 EP400 BCAT1 VRK1 MECOM MORF4L1 H2AFX EEF1A2 CACNA1D USP33 ANPEP PHB2 RPL35 DMGDH ARL9 KTI12 DYNC2H1 PUS1 TPT1 GCLC LTA4H BIN3 PPP6R3 TRAPPC6A ZFP42 RRAGA PPAT SDHB ALDH1L2 CYB5R1 GGPS1 TAPT1 PPIL6 SLC11A2 XPO5 AVL9 COQ7 PRKG2 SH3YL1 SORT1 TRMT10B PPTC7 RPL7 GAPDH LIPT2 CCNA2 AP3D1 OPLAH AP3S2 ERCC8 STX2 HLTF MGAM2 RCE1 VAMP2 NKTR RPSA SLC26A11 SIRT2 EEF2 CYCS HCFC2 TMED9 PHGDH HGH1 IDO1 ALLC RWDD1 SLC25A4 RPL23 PHGDH SLC25A3 ZDHHC18 ABHD5 GPX7 show allhide
Negative interactions	BECN2 CHMP5 STAM2 VPS35 VPS13D ARHGAP11A ARHGAP29 PIF1 VPS29 KIFC2 ATG3 PGAP1 KATNA1 RAB5B PPP2R5C PRDX1 ELOVL1 PPCDC CRLS1 GEN1 RAD52 TIPRL TMEM165 DICER1 RPL24 RPL14 SLC47A2 RAB7A TGFBRAP1 UBR3 VPS8 VPS41 SIGMAR1 HAGHL MTFMT CSNK2A2 RBM34 BBOX1 SNAPC4 YEATS4 PMS1 NIT1 AMPD1 ASF1A ABCD3 CHMP3 VAPB DDX11 DOHH GOLPH3L AZIN2 NEK1 TSSK3 ARL14 CHTF18 FAF1 CLCN2 RPS16 BRSK1 ZFP42 SC5D PSMA4 IDH3B WIPI2 ELOVL1 CRAT RPS29 PDHA2 PXMP2 SFXN1 RPS7 STK39 LSM7 VRK1 FKBP1A RPS4X EPS15 AMD1 RPL17-C18orf32 STX16-NPEPL1 RNASEH2A MRI1 PGRMC2 OSBP RAB5B SRM PPP6C CWF19L1 FAU AGXT RPS10 LENG8 CHMP1A TARBP1 SLC15A4 SNX8 RPL9 ATP10B CHAC1 CANX CCNA2 RAD51 RPL22L1 PTRH1 HEMK1 VPS26B BRSK1 PPIP5K1 POMT2 SLC12A8 TOMM70 ONECUT1 UBA3 RPS6 SHMT2 SEL1L KDM4A MYO15B PFKFB2 HGS MSH2 GLIPR2 FAU METTL18 UBE2D3 DRG2 PPME1 FIGNL2 SRR VAC14 OSGEPL1 GRK7 USP17L30 IMMP2L HSPA4L IDH2 ANKZF1 RIT1 PGLS SGPP2 RPL27 RPS16 ATG7 TSR3 BTF3L4 XPNPEP3 NAALAD2 ELP3 PLAA MOV10 OVCA2 TTC37 PPM1B CCNA2 OLA1 AK4 CCDC25 ASNS TCP11L2 RPL36 CDC25B WDR26 TRMT12 CHKA PDPK1 PLD1 DBT FBP1 NEDD8 UBXN7 PIGG POMT2 PGLS RASA2 MOGAT3 PTPRN2 ISYNA1 HAAO GK5 ETFA show allhide

Modifier statisitcs

Record:

Disorder:

Vriant:

Reference:

Effect type:

Pleiotropy(1)

Modifier effect:

Altered the contributing organ(1)

Detail：

Variant 1:

ATP12A:c.2512-683C>T

Gene:

ATP12A

Genomic location:

dbSNP ID:

rs61948108

Target disease:

Cystic fibrosis(DOID_1485)

Effect type:

Pleiotropy

Modifier effect:

Altered the contributing organ

Evidence:

P=3.83×10(-10)

Effect:

The associated modifier loci colocalized with expression quantitative trait loci in the pancreas

Reference:

PMID30807572

Title:

Genetic association and transcriptome integration identify contributing genes and tissues at cystic fibrosis modifier loci.

Species studied:

Human

Abstract:

Cystic Fibrosis (CF) exhibits morbidity in several organs, including progressive lung disease in all patients and intestinal obstruction at birth (meconium ileus) in ~15%. Individuals with the same causal CFTR mutations show variable disease presentation which is partly attributed to modifier genes. With >6,500 participants from the International CF Gene Modifier Consortium, genome-wide association investigation identified a new modifier locus for meconium ileus encompassing ATP12A on chromosome 13 (min p = 3.83x10(-10)); replicated loci encompassing SLC6A14 on chromosome X and SLC26A9 on chromosome 1, (min p<2.2x10(-16), 2.81x10(-11), respectively); and replicated a suggestive locus on chromosome 7 near PRSS1 (min p = 2.55x10(-7)). PRSS1 is exclusively expressed in the exocrine pancreas and was previously associated with non-CF pancreatitis with functional characterization demonstrating impact on PRSS1 gene expression. We thus asked whether the other meconium ileus modifier loci impact gene expression and in which organ. We developed and applied a colocalization framework called the Simple Sum (SS) that integrates regulatory and genetic association information, and also contrasts colocalization evidence across tissues or genes. The associated modifier loci colocalized with expression quantitative trait loci (eQTLs) for ATP12A (p = 3.35x10(-8)), SLC6A14 (p = 1.12x10(-10)) and SLC26A9 (p = 4.48x10(-5)) in the pancreas, even though meconium ileus manifests in the intestine. The meconium ileus susceptibility locus on chromosome X appeared shifted in location from a previously identified locus for CF lung disease severity. Using the SS we integrated the lung disease association locus with eQTLs from nasal epithelia of 63 CF participants and demonstrated evidence of colocalization with airway-specific regulation of SLC6A14 (p = 2.3x10(-4)). Cystic Fibrosis is realizing the promise of personalized medicine, and identification of the contributing organ and understanding of tissue specificity for a gene modifier is essential for the next phase of personalizing therapeutic strategies.