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Report for Clinical Trial NCT01739231

Developed by Shray Alag, 2020.
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 352
PCSK1 MPV17 SON AK2 CYP27A1 HNF1A ERCC2 BTK LIG4 STX3 PALLD TCIRG1 RNF168 TYMP GREM1 ANTXR2 IGKC GINS1 RFX5 TERT PTEN PKP1 WIPF1 SLC25A13 RFXANK TYMP HYOU1 HLA-B CPT1A ENG FBP1 SERPING1 BMPR1A TGFB1 MAOA SDHD ACTG2 HMGCL CD55 TREH IDS STAT4 CDKN2B TLK2 PMM2 WAS BMPR1A DNAJC6 C5 AP1S1 SCNN1B CD247 CDKN2C TSHR BMPR1A GFI1 NBN ITGA2 ENG HSD3B7 NAXD RFXANK IFNGR1 NOD2 SUGCT NOD2 HEXB IL21R RFXAP TTC7A SLC39A4 IL2RB DDC CYP7B1 STAT1 ABCC8 ANTXR2 RIPK1 OPLAH RECQL4 SLC9A3 SMAD4 PHKB RAG2 LCT ALG8 MLYCD SLC7A7 ALDOB SLC19A2 MYD88 CCDC47 GLA IDUA GP1BA SI BRCA2 BTD SERPING1 CPOX NEUROG3 IL10RA CIITA SEMA3C ABCB4 ADA PLVAP UCHL1 SAMD9 SCNN1G ALAD WNT2B CIITA TNFRSF1A IL7R LCK ICOS MEN1 RET MEFV PARK7 NAGLU PIGT RAG2 COG4 SCNN1A IGHM SLC46A1 PLEC ETHE1 PTPRC LIG4 TP53 BLM ACAT1 SLC10A2 MC2R RFX5 RAG2 ITCH DNASE1L3 CFH EGFR IL2RG COG6 CYP11B2 TTR PODXL SLC39A4 ELP1 HTRA2 RNF113A ACSF3 HGSNAT CD3E ADA ATP7A TCF3 MEN1 MYO5B ACADM SLC26A3 AVP SEMA3D ZAP70 TSHR SAR1B IGHM AGA TCN2 CDKN2A NBN POLG MCM6 ADAM17 DGAT1 DES ECE1 TTC37 CD247 NAGS CFHR1 SLC7A7 NRTN BLNK TXNRD2 BLNK CR2 ATP8B1 ITGB4 RAG1 SNCA TTC37 ARX GNS SERPING1 CD79B RAG1 GP1BB VPS13C CD79A TFRC EFL1 NNT UCP2 SRP54 NLRC4 FOXP3 RET LRBA KIF1B CD3D MYO5B CYP27A1 KRAS TNFRSF13B C1R LIPA DCLRE1C DBH DCLRE1C SKIV2L PRKN LRRC8A ICOS NSUN2 CTLA4 CARMIL2 ITGB3 IL7R LIPA GATA6 HMBS SMAD4 EDNRB TTC7A SKIV2L JAK3 G6PC IL2RG CASP8 RFX6 RAG1 PINK1 CLMP IGLL1 HPS1 ITGA2B IL21 SPP1 TNFRSF13C JAK3 ABCB11 CD79A IL7R IL6 CDKN1A GALT BRCA1 EPCAM POLA1 CD19 CFHR3 CR2 STAT1 CD3D FOXP3 SPINT2 GDNF AIRE GUCY2C NHLRC2 AKR1D1 WAS MPI DCLRE1C IL2RA IKBKB KCNJ1 SGSH SP110 SAR1B MVK IKZF1 ATRX SAA1 SMAD4 STAR DAXX MRAP SLC12A3 BTK POLG MVK EDN3 CD109 OTULIN HNF4A SLC5A1 NCF4 COG4 RAG1 PIK3R1 SLC46A1 CDKN1B CHD7 SLC12A1 MGME1 HADH SMARCD2 B2M C1QA CD40LG BTK TMPRSS15 LRRK2 ZAP70 APC CD79B TTR ALG3 NR3C2 RECQL4 ITGA6 RAG2 SMAD4 IRAK1 RFXAP ACSF3 ELANE BMPR1A KCNJ11 IL2RG PALB2 SCN11A ACVRL1 ADA PIK3R1 MGME1 SCN9A MVK HMGCS2 CLCNKB CDKN1B SLC25A13 NEUROG3 RMRP RRM2B KIF23 ETHE1 DNMT3B PPP2R5D