SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01739231

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Safety, Reactogenicity, Tolerability, Immunogenicity and Efficacy of Live Attenuated ETEC ACE527 Vaccine Administered Alone or With a Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Volunteers

This is a research study about an experimental (investigational) oral ETEC vaccine (ACE527). ACE527 is a live attenuated vaccine that is being made to prevent disease from enterotoxigenic Escherichia coli (ETEC), which causes watery diarrhea, largely in children living in developing countries and in travelers to those countries. This research study is also testing an investigational adjuvant called dmLT. An adjuvant is something that is added to a vaccine to make it work better. The purpose of this study is two-fold. First, Part A aims to find out if the vaccine by itself or the vaccine combined with the adjuvant is safe, tolerable, and initiates an immune response. Second, Part B aims to find out if the vaccine by itself or the vaccine combined with the adjuvant prevents diarrheal disease when challenged with ETEC H10407. About 60 healthy adults, ages 18-50, will participate in Part A, and they will be required to stay in the research facility for several nights for the first dose, but will not be required to stay overnight for the second and third doses. Participants will be assigned to receive either the vaccine alone, the vaccine with adjuvant, or placebo by mouth. Study procedures include: stool samples, blood samples, and documentation of side effects. Participants will be involved in study related procedures for about 8 months. Interested volunteers from Part A will along with volunteers who were never vaccinated in Part A will return to participate in Part B. These volunteers will be required to stay overnight in the research facility for several nights after challenge, after which they will be treated with antibiotics and sent home. Study procedures include stool samples, blood samples, and documentation of infection with ETEC H10407. If the vaccine with/without adjuvant is effective, the volunteers should not development diarrhea, but if the vaccine with/without adjuvant is not effective, the volunteers will have diarrhea for a few days.

NCT01739231 Diarrhea
MeSH: Diarrhea
HPO: Diarrhea

4 Interventions

Name: ACE527

Description: 3x10^9 cfu ACE527 vaccine strain. Comprised of three genetically attenuated and engineered strains of E. coli, with antigen profiles covering a wide range of ETEC surface colonization factor antigens (CFA/I, CFA/II [CS1, CS2, CS3] and CFA/IV [CS5, CS6]) and also expressing LTB, the inactive subunit of LT (ETEC heat labile toxin). The constituent strains of ACE527 were: ACAM2025: a live, attenuated, CFA/I, LTB positive strain ACAM2022: a live, attenuated, CS5, CS6, LTB positive strain, and ACAM2027: a live, attenuated, CS1, CS2, CS3, LTB positive strain.

Type: Biological

ACE527 alone ACE527 plus dmLT

Name: dmLT

Description: A derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine (13). These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.

Type: Biological

ACE527 plus dmLT

Name: CeraVacx placebo

Description: CeraVacx® is used to neutralize gastric acidity upon ingestion of vaccine. It was also used as the placebo in this study. CeraVacx® was prepared from the commercial product (Cera Products, Inc.); 9.5 grams were added to sterile water for each dose and mixed. Each dose contained 7 grams of rice syrup, 2 grams of sodium bicarbonate, and 0.5 grams of trisodium citrate.

Type: Biological

Control: Part A and B

Name: H10407 challenge strain

Description: Approximately 2 x 10^7 cfu of the fully virulent ETEC strain. Previously administered to 91 volunteers at this challenge dose by the CIR clinical team over the previous 4 years in conjunction with other Phase 1/2b trials.

Type: Biological

ACE527 alone ACE527 plus dmLT Control: Part A and B Control: Part B only


Primary Outcomes

Description: Unsolicited adverse events were collected throughout Part A of the study, were graded for severity, and assessed for relationship to vaccine. Withdrawal from the study due to adverse event was determined at the discretion of the study staff.

Measure: Part A: Number of Serious Adverse Events and Adverse Events Leading to Withdrawal

Time: up to 1 month after last vaccination (3 months)

Description: Unsolicited adverse events were collected throughout Part A of the study, were graded for severity, and assessed for relationship to vaccine. Generally, mild severity is discomfort with no disruption of normal daily activities and relieved with or without symptomatic treatment; moderate severity is discomfort sufficient to reduce or affect normal daily activity somewhat and only partially relieved with symptomatic treatment; and severe is discomfort sufficient to reduce or affect normal daily activity considerably; prevents regular activities, and not relieved with symptomatic treatment. Additional description of severity for diarrhea, body temperature, and vomiting is described in the protocol.

Measure: Part A: Number of Participants Experiencing Unsolicited Adverse Events, by Severity and Relationship to Vaccination

Time: up to 1 month after last vaccination (3 months)

Description: Solicited reactions were collected 1 week after each vaccination.

Measure: Part A: Number of Solicited Reactions

Time: up to 1 week after each vaccination (at 0, 1, and 2 months)

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Pre all vaccinations; day 3 post-vaccination 1 and 2; day 7 post all vaccinations; 4 weeks post-vaccination 3

Description: Defined as a four-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

Measure: Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Defined as a 2.5-fold rise or greater in geometric mean titer.

Measure: Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

Time: Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

Measure: Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

Time: Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

Description: Severe diarrhea was defined as >800 grams of grade 3-5 stools passed over the 120-hour observation period. For episodes starting at or before 120 hours post-challenge, volunteers were followed to resolution and the total stool output weight was considered in determining whether a specific volunteer met the primary definition of severe diarrhea. The end of a diarrheal episode occurred when a volunteer did not pass any grade 3-5 stool in a 24-hour period. Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Number and Percentage of Subjects Experiencing Severe Diarrhea Following H10407 Challenge Strain

Time: 5 days

Secondary Outcomes

Measure: Part A: Number of Participants Shedding E. Coli on Qualification Plate

Time: Pre- and day 7 post-all vaccinations; and Day 3 post-vaccinations 1 and 2; and 4 weeks post vaccination 3

Measure: Part A: Number of Participants With Positive Shedding Results for ACE527

Time: Pre- and day 7 post-all vaccinations; and Day 3 post-vaccinations 1 and 2; and 4 weeks post vaccination 3

Measure: Number of Participants Shedding Vaccine Strains Included in ACE527

Time: 3 days after the first and second vaccinations

Description: Defined as mild, moderate, or severe diarrhea, specifically: Mild diarrhea: 2 or 3grade 3-5 stools totaling 200 g - 400 g, or 1 grade 3-5 stool of >300 g Moderate diarrhea: 4-5 grade 3-5 stools totaling >200 g or 401 - 800g Severe diarrhea: > 800g grade 3-5 stool(s) Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Number and Percentage of Subjects Experiencing Diarrhea of Any Severity

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Mean Total Weight of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Median Total Weight of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Mean Number of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Median Number of Grade 3-5 Stools Passed Per Volunteer

Time: 5 days

Description: Solicited reactions were generally graded as mild if there was discomfort, but no disruption of normal daily activities; moderate if if discomfort was sufficient to affect normal daily activity and partially relieved with symptomatic treatment; severe if discomfort was sufficient to affect normal daily activity considerably, prevent regular activity, and not relieved with symptomatic treatment.

Measure: Part B: Number of Subjects Experiencing Solicited Reactions Graded as Moderate or Severe

Time: 1 week

Description: When asking about adverse events, subjects were asked whether their illness resulting from ETEC would have reduced their daily activity because of their illness if they had been vacationing or traveling on business.

Measure: Part B: Number and Percentage of Subjects Who Would Have Reduced Daily Activity

Time: 5 days

Description: Defined as mild, moderate, or severe diarrhea, specifically: Mild diarrhea: 2 or 3grade 3-5 stools totaling 200 g - 400 g, or 1 grade 3-5 stool of >300 g Moderate diarrhea: 4-5 grade 3-5 stools totaling >200 g or 401 - 800g Severe diarrhea: > 800g grade 3-5 stool(s) Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

Measure: Part B: Mean Time to Onset of Diarrhea Among Subjects Who Had Diarrhea

Time: 5 days

Measure: Part B: Quantity of H10407 Per Gram of Stool on Day 2 Post-challenge

Time: 2 days after vaccination

Measure: Part B: Number of Subjects Requiring Early Antibiotic Treatment and Intravenous (IV) Fluids

Time: 5 days

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 R192G

LT(R192G/L211A), or dmLT, is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. --- R192G ---



HPO Nodes


HPO:
Diarrhea
Genes 251
CDKN1A HEXB PCSK1 CDKN1B IL10RA CDKN2A CDKN2B CDKN2C MYD88 SCN11A TMPRSS15 ERCC2 SAMD9 ATP7A PLVAP RNF168 GALT MAOA RIPK1 ATRX HLA-B MYO5B ACAT1 AVP B2M CYP27A1 RNF113A NAGLU CD109 MC2R AKR1D1 BLNK GATA6 CD55 ITGA6 ACTG2 TCIRG1 HMBS SRP54 NBN MCM6 DAXX IKZF1 NCF4 SLC46A1 HMGCL DBH ATP8B1 TSHR HMGCS2 NHLRC2 ITGA2 ITGA2B ACVRL1 PTEN ADA HNF4A NSUN2 ITGB3 ITGB4 DDC GDNF TTR GINS1 GFI1 MEFV STAR NAGS NLRC4 STAT1 ABCB4 MEN1 BLM JAK3 PHKB DES SAA1 BMPR1A AP1S1 STX3 FBP1 ICOS ANTXR2 PTPRC OTULIN GLA BRCA1 BRCA2 CLCNKB CIITA COG6 CCDC47 BTD KCNJ1 AGA PIK3R1 ABCC8 BTK KCNJ11 UCP2 RECQL4 HPS1 IL21 SCN9A SCNN1A SCNN1B SCNN1G PKP1 SERPING1 ACSF3 AK2 CYP7B1 ALG8 ALAD NR3C2 ADAM17 C5 PLEC NME1 ALDOB COG4 GNS DNASE1L3 SDHD OPLAH GP1BA GP1BB DNMT3B PMM2 FOXP3 MPI TLK2 KRAS MPV17 RAG1 RAG2 EFL1 HNF1A SEMA3C TCF3 SLC26A3 KIF23 ITCH CARMIL2 HYOU1 WAS WIPF1 TCN2 NRTN POLA1 SGSH RRM2B POLG ARX SLC19A2 HGSNAT APC ELP1 AIRE CASP8 SI SLC39A4 RFX6 CHD7 CPOX TXNRD2 RET LCK CPT1A IDS SLC7A7 ECE1 IDUA TYMP LCT SKIV2L CR2 SP110 RFX5 RFXAP ZAP70 PALB2 EDN3 EDNRB MLYCD SLC5A1 TFRC TTC7A IFNGR1 RMRP LIG4 SEMA3D HSD3B7 CD3D PIGT LIPA SLC9A3 CD247 PPP2R5D SLC10A2 SPINT2 SLC12A1 SLC12A3 CD19 EGFR DCLRE1C SUGCT GUCY2C TREH RFXANK ETHE1 IGHM TTC37 MRAP IL21R SAR1B IGKC NAXD CD40LG TNFRSF13C LRRC8A ABCB11 ELANE TNFRSF13B SMARCD2 CD79A CD79B CLMP ALG3 CTLA4 IGLL1 GREM1 HADH LRBA TNFRSF1A IKBKB ENG IL2RA EPCAM IL2RG G6PC NNT PALLD NEUROG3 TP53 DGAT1 MVK IL7R SMAD4 MGME1 SON