SNPMiner Trials by Shray Alag


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Report for SNP rs4869676

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 Clinical Relevance of miR-142-3p as Potential Biomarker of Synaptopathy in Multiple Sclerosis

Inflammatory synaptopathy is a prominent pathogenic mechanism in multiple sclerosis (MS) and in its mouse model, which can cause excitotoxic damage by long-lasting excessive synaptic excitation and, consequentially, drives disease progression by leading to motor and cognitive deficits. As synaptopathy occurs early during the disease course and is potentially reversible, it represents an appealing therapeutic target in MS. Although reliable biomarkers of MS synaptopathy are still missing, recent researches highlighted miR-142-3p as a possible candidate. Indeed, miR-142-3p has been described to promote the IL-1beta-dependent synaptopathy by downregulating GLAST/EAAT1, a crucial glial transporter involved in glutamate homeostasis. Furthermore, mir-142-3p has been suggested as a putative negative MS prognostic factor and a target of current MS disease modifying therapies. The hypothesis of this study is that miR-142-3p represents a good biomarker for excitotoxic synaptopathy to predict MS course, and, possibly, treatment efficacy at individual level, including both pharmacological strategies and non-pharmacological interventions, like therapeutic transcranial magnetic stimulation (TMS) to ameliorate MS spasticity. To this aim, the role of miR-142-3p in MS synaptopathy, its potential impact on the efficacy of disease-modifying treatments currently used in MS therapy as well as the influence of genetic variants (SNPs) of miR-142-3p and GLAST/EAAT1 coding genes on the responsiveness to therapeutic TMS, will be further investigated in the study. By validating miR-142-3p as potential biomarker of synaptopathy, it is expect to improve MS prognosis and personalized therapies. Patients with MS, who will undergo neurological assessment, conventional brain MRI scan, and CSF and blood withdrawal for diagnostic and clinical reasons at the Neurology Unit of IRCCS INM-Neuromed will be enrolled in the study. Neurophysiological, biochemical and genetic parameters together with lower limb spasticity will be evaluated. Subjects, who will undergo blood sampling and/or lumbar puncture for clinical suspicions, later on not confirmed, will be recruited as control group. A subgroup of MS patients showing lower limb spasticity will be included in a two-week repetitive TMS stimulation protocol (iTBS) to correlate the patient responsiveness to this non-pharmacological treatment with MS-significant SNPs of both miR-142-3p and GLAST/EAAT1 coding genes.

NCT03999788 Multiple Sclerosis Spasticity Procedure: lumbar puncture and blood withdrawal Procedure: Intermittent theta burst stimulation (iTBS) therapeutic protocol for spasticity
MeSH: Muscle Spasticity Multiple Sclerosis Sclerosis
HPO: Spasticity

The following SNPs in MIR142 gene coding for miR-142-3p: rs550842646, rs377637047, rs562696473, rs529802001, rs547987105, rs573562920, rs544684689 and rs549927573, and in SLC1A3 gene coding for GLAST/EAAT1: rs137852620, rs2032892, rs2562582, rs4869675, rs4869676, rs2269272, rs2269273, rs1049522, rs1049524 and rs2731886, will be analyzed.

Primary Outcomes

Description: Quantification of CSF levels of miR-142-3p by qPCR analysis. Relative quantification will be performed by 2^(-ddCt) method.

Measure: CSF concentration of miR-142-3p

Time: T0 (enrollment); MS patients vs Control subjects

Description: Quantification of CSF inflammatory molecules (TNF, IL-1β, IL-6, IL-17, IFN-γ, IL1ra, IL-22, IL-2, IL-2ra, IL-10, IL-4, IL-5, IL-13, IL-12p40, IL-8) by Luminex multiplex assays; neurofilaments, beta amyloid, tau proteins and growth factors (like NGF, PDGF and BDNF) by Luminex multiplex assays. Data will be expressed as pg/ml.

Measure: CSF concentration of soluble molecules

Time: T0 (enrollment); MS patients vs Control subjects

Description: Clinical disability will be certified by a qualified neurologist through the Progression Index (PI) calculated as EDSS combined with disease duration (EDSS/disease duration). Disease duration is estimated as the number of years from onset to the most recent assessment of disability and EDSS scale ranging from 0 to 10 in 0.5 unit increments that represent higher levels of disability.

Measure: Clinical disability assessment by Progression Index calculation for correlation analysis with CSF-miR-142-3p levels

Time: Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up

Description: The Multiple Sclerosis Functional Composite (MSFC) is a three-part composite clinical measure. Three variables were recommended as primary measures: Timed 25-Foot walk; 9-Hole Peg Test; and Paced Auditory Serial Addition Test (PASAT- 3"). The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each patient at each time point. There are 3 components: the average scores from the four trials on the 9-HPT; the average scores of two 25-Foot Timed Walk trials; the number correct from the PASAT-3. The scores for these three dimensions are combined to create a single score that can be used to detect change over time. This is done by creating Z-scores for each component. MSFC Score = {Zarm, average + Zleg, average + Zcognitive} / 3.0 (Where Zxxx =Z-score) Increased scores represent deterioration in the 9-HPT and the 25-Foot Timed Walk, whereas decreased scores represent deterioration in the PASAT-3.

Measure: Clinical disability assessment by MSFC calculation for correlation analysis with CSF-miR-142-3p levels

Time: Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up

Description: By conventional MRI (1.5 Tesla) the following parameters will be evaluated: dual-echo proton density, FLAIR, T1-WI, T2-WI, and contrast-enhanced T1-WI after intravenous gadolinium (Gd) infusion (0.2 ml/kg). A new Gd+ lesion is defined as a typical area of hyperintense signal on postcontrast T1-WI. A new or newly enlarging lesion on T2-WI is defined as a rounded or oval lesion arising from an area previously considered as normal appearing brain tissue and/or showing an identifiable increase in size from a previously stable-appearing lesion. An active scan is defined as showing any new, enlarging or recurrent lesion(s) on postcontrast T1- and T2-WI.

Measure: Neuroradiological assessment for correlation analysis with CSF-miR-142-3p levels

Time: Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up

Description: To assess synaptic excitability by SICI, ICF and LICI, motor thresholds will be calculated at rest as the lowest stimulus intensity able to evoke MEPs of about 50uV in 5 out of 10 consecutive trials (cts), and during a slight voluntary contraction of the target muscle (20-30% of the max voluntary contraction) as the lowest intensity able to evoke MEPs > 100uV in 5 out of 10 cts. The mean peak-to-peak amplitude of the conditioned MEP (cMEP), at each interstimulus interval (ISI), will be expressed as a percentage of the mean peak-to-peak amplitude of the test MEP (tMEP). PAS-induced LTP-like plasticity will be expressed as changes of the average MEPs size at each time point after PAS compared to the average baseline MEPs size. Before PAS, 25 MEPs, evoked by single TMS pulses over the APB motor hot spot set at an intensity to obtain MEPs size of about 1mV peak-to-peak, will be collected. The same stimulus intensity will be used to obtain 25 MEPs 0', 30' and 60' after PAS.

Measure: Neurophysiological assessments for correlation analysis with CSF-miR-142-3p levels

Time: Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up

Description: To investigate miR-142-3p association with synaptopathy-driven disease progression (measured in terms of clinical or radiological changes and TMS variables), multivariable generalized linear models (GLM) will be applied considering miR level in the CSF as an independent variable adjusting for demographical, clinical, neuroradiological, neurophysiological, biochemical factors and treatments. In the case of unsuccessful identification, Principal Component Analysis (PCA) will be performed to evaluate the miR contribution with other molecules in the CSF (as cytokines, chemokines, growth factors, neurofilaments, beta amyloid and tau protein) to synaptopathy-driven disease progression to reduce the number of variable examined and increase the power of multivariate analysis. Statistical correlations will be repeated on the identified PCA components including miR-142-3p as part of the component. The significance level is established at p<0.05.

Measure: Statistical correlation of miR-142-3p levels in MS CSF with disease and neurophysiological parameters

Time: T0 (enrollment), T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months).

Secondary Outcomes

Description: miR-142-3p levels in the CSF will be assessed at T0, as reported above. The responsiveness to the DMT, who MS patients underwent as part of their clinical routine, will be evaluated according to clinical and neuroradiological parameters considered in the primary outcomes. Changes in such parameters will be evaluated at different time points during a six-year follow-up (T12-T0; T24-T0, T24-T12, etc). Both univariable and multivariable approaches and stratification of patients based on DMT treatment will be performed.The significance level is established at p<0.05.

Measure: Statistical correlation of miR-142-3p levels in MS CSF with patient's responsiveness to disease modifying therapies (DMTs).

Time: Time Frame: T0 (enrollment); Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up

Description: Genetic screening will be performed on peripheral blood withdrawn from MS patients at T0. The following SNPs in MIR142 gene coding for miR-142-3p: rs550842646, rs377637047, rs562696473, rs529802001, rs547987105, rs573562920, rs544684689 and rs549927573, and in SLC1A3 gene coding for GLAST/EAAT1: rs137852620, rs2032892, rs2562582, rs4869675, rs4869676, rs2269272, rs2269273, rs1049522, rs1049524 and rs2731886, will be analyzed. Univariable and multivariable correlations of minor allele presence of each screened SNP with clinical, neuroradiological and neurophysiological parameters, detected in the primary outcomes (T0, T12, T24, T36, T48, T60, T72), will allow the identification of SNPs relevant to disease progression. The significance level is established at p<0.05.

Measure: Genotyping of SNPs in SLC1A3 and MIR-142 genes for correlation analysis with disease parameters

Time: Time Frame: T0 (enrollment); Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up

Description: Lower limb spasticity will be evaluated in all recruited MS patients at T0 and during 6-year-follow-up. A subgroup of MS patients with lower-limb spastic symptoms and carrying SNPs in in SLC1A3 and MIR-142 genes relevant to disease progression will undergo therapeutic iTBS protocol daily for two weeks (interventional substudy) and spasticity will be assessed also immediately before the beginning (W0) and after 2 weeks at the end of the protocol (W2). The H/M amplitude ratio of the Soleus H reflex will be evaluated by EMG recordings as an index of spinal excitability. Compound motor action potentials (cMAPs) and H reflex will be evoked by electrical stimulation of the tibial nerve. The maximum amplitudes of the H reflex (H) and CMAP (M) potentials will be measured from peak to peak and H/M ratio was calculated by dividing the maximal amplitude of H wave by that of M wave.

Measure: Lower limb spasticity assessment by H/M amplitude ratio for the therapeutic TMS substudy

Time: Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up; Changes from the starting day (W0) to the end of the 2-week iTBS protocol (W2).

Description: Lower limb spasticity will be evaluated in all recruited MS patients at T0 and during 6-year-follow-up. A subgroup of MS patients with lower-limb spastic symptoms and carrying SNPs in in SLC1A3 and MIR-142 genes relevant to disease progression will undergo therapeutic iTBS protocol daily for two weeks (interventional substudy) and spasticity will be assessed also immediately before the beginning (W0) and after 2 weeks at the end of the protocol (W2). The Modified Ashworth Scale (MAS) assesses resistance during passive soft-tissue stretching ranging from 0 to 4 score.

Measure: Lower limb spasticity assessment by MAS score for the therapeutic TMS substudy

Time: Changes from T0 (enrollment) to T12 (12 months), T24 (24 months), T36 (36 months), T48 (48 months), T60 (60 months) and T72 (72 months) of follow-up; Changes from the starting day (W0) to the end of the 2-week iTBS protocol (W2).

Description: Minor allele presence of each screened SNP in SLC1A3 and MIR-142, identified at T0 as relevant to disease progression (see above), will be correlated with changes in spasticity parameters (the H/M amplitude ratio of the Soleus H reflex and MAS score) upon the iTBS treatment (W2-W0). The significance level is established at p<0.05.

Measure: Statistical correlation of response to iTBS treatment with MS-significant SNPs of both SLC1A3 and MIR-142.

Time: T0 (enrollment); Changes from the starting day (W0) to the end of the 2-week iTBS protocol (W2).


HPO Nodes


Spasticity
Genes 1056
NUS1 ARX PLAA L1CAM CLPB FBXO7 WDR45 NACC1 ALS2 CYP27A1 ATXN3 GFM2 OPA1 ARL6IP1 GPHN CTC1 SNORD118 MFSD2A KANK1 EML1 AMPD2 NDUFV2 TREX1 FGFR1 POLR1C SQSTM1 LMNB1 GABRA2 AP5Z1 NDUFAF4 PON2 YWHAG IRF2BPL WDR4 GRIN1 OPTN HMGCL PNPLA6 PSAP SCN3A CACNA1G DNAJC6 DSTYK OTUD6B TRAK1 WDR73 GNAO1 RAB27A MAN1B1 RARS1 ERLIN2 PGAP1 TREX1 ERCC4 CRLF1 DENND5A GABRG2 AIFM1 SPG7 SDHA KIF5A GBA2 L1CAM DHCR24 CACNA1G NUBPL TYROBP FUS NPC2 TMEM67 GPHN GRIA4 CYB5A ERCC6 ERCC5 GBA SPG7 ISCA2 RNASEH2C PRSS12 CNTNAP2 PNPLA8 PEX5 HTT RAB3GAP2 OPA1 UCHL1 LIPT2 ARX NEFL TNIK NDUFS1 PCLO VPS53 KIF11 COASY RAB3GAP1 LAMB1 ATP13A2 SLC17A5 HLA-DQB1 C12ORF65 BCL11B ATXN3 ATL1 RAB11B REPS1 NOTCH3 LINS1 NSUN2 GPT2 GBE1 WDR73 RLIM ALDH18A1 CHP1 KDM5B B3GALNT2 NDUFAF2 DYNC1I2 TTR AGTPBP1 PODXL ATRX AP4E1 ACP2 VAMP1 PEX13 HPRT1 SCYL1 ZC3H14 PEX12 GJC2 EDC3 ECHS1 CTSD FMN2 PRRT2 GPT2 HSPD1 B4GALNT1 PDHX SDHAF1 GTF2I SLC25A22 AASS ATP6V0A2 NDE1 KIF2A TUBA1A SLC6A5 MPLKIP MAPT ERCC2 GABBR2 RUSC2 MOCS1 EZR PAFAH1B1 BCS1L C19ORF12 ND4 SOX4 SPG11 SDHA ANG CC2D1A ALDH18A1 EXOSC8 MED17 AFG3L2 KCNJ6 PRKN CACNA1B SLC2A1 PEX10 AP4M1 HNRNPA1 ATXN10 CFAP410 ATAD3A FLRT1 UFM1 GAN PNPLA6 SPG11 FA2H C9ORF72 CAPN1 MARS1 NDUFAF5 SMPD1 PANK2 CLP1 NDUFB8 CHCHD10 GJC2 AARS1 TRAK1 CCT5 SYNGAP1 ZFR ARL6IP1 COX15 INPP5K PLP1 WWOX NEXMIF RAB3GAP2 DDHD1 GABRB2 GUF1 PSAP KCNA2 C12ORF4 RERE L1CAM NDUFA12 PFN1 ALDH18A1 CTNNB1 ATXN8 KMT2B SETX PNPLA6 SIGMAR1 FTL GLRA1 EZH2 EED STN1 DAO LIAS GABRB2 UCHL1 BSCL2 GTF2E2 PIGA POLR3A NUS1 RNASEH2A FGF12 FBXO7 ARX LRRK2 TRAPPC9 MTFMT TPK1 EEF1A2 OSTM1 RTN2 ERCC2 NTRK2 SOX10 TRIM8 PEX3 HEPACAM C12ORF65 ERBB4 SPATA5 CAMK2A ENTPD1 SLC2A1 SLC30A10 SPG21 NEK1 ERCC5 FOXRED1 ATAD3A TRNK ATP6 WASHC4 MARS2 CLTC ERCC3 SLC1A2 TBCD RNASEH2B EPM2A SYNJ1 TRNF NEFH DLD ABCC8 ATXN2 AIMP1 REEP2 DHDDS KCNA1 KLC2 SON REEP1 RTTN ERCC2 SLC2A1 SCN8A NAGA KCNA2 SLC25A15 PEX6 UBQLN2 ASPA IREB2 ATRX RFC2 PLA2G6 MCCC1 NDUFS3 CLCN4 PLA2G6 REEP2 SUMF1 TARDBP TBC1D20 NDUFS4 PTS ATP6AP2 SIK1 ERLIN1 L1CAM DDHD1 MFN2 POLR3B NHLRC1 VPS13C CYB5R3 RPGRIP1L PRPS1 PSAP GFAP WDR62 FA2H ARSA ADAT3 COG2 ERCC3 MACF1 GBE1 TAF2 SCN2A ARF1 SLC25A12 PQBP1 PLP1 INPP5K ANK3 NUP214 TFG PHGDH IDUA DNM1 ALS2 AP4B1 UBAP1 PIGC PANK2 COLGALT1 CC2D2A ARX RANBP2 PUM1 ATXN2 RNASEH2A ARX GBA2 ELN CLCN4 COL4A2 BOLA3 EIF2B3 MATR3 SLC39A14 SNCA EDNRB NEFH NT5C2 MICOS13 ZNF592 IKBKG ANXA11 ATP6 SLC25A22 BICD2 FIG4 ROGDI VAPB ACAT1 NTRK2 PRDM8 HTT C19ORF12 TIMM50 ATXN8 MRE11 TAF1 JAM3 TOE1 HTRA2 NKX6-2 CRADD GRIN2B MFF CYFIP2 DDX3X EPRS1 ALG11 WDR48 AMPD2 SLC33A1 GBA SNX14 TFG SLC13A5 ATP7A CLIP1 RARS2 CPT1C TDP1 ND3 CASK ATP6V1A AP3B2 PON1 TELO2 MRPS34 HLA-DRB1 AFG3L2 ARX PRNP TAF1 KCNJ6 KIF1C EPHA4 ARV1 MECP2 DCTN1 ERLIN1 ALS2 ARSA PAX3 GRM1 POLA1 GJA1 HSPD1 UBA5 GSS ADAM22 SLC13A5 SPG11 UFC1 PAX3 POLR3B LIPT1 ERCC3 CARS2 NARS2 PQBP1 PEX11B CLIC2 TOE1 ATXN7 PPARGC1A OCLN RNASEH2B FTL ST3GAL3 CYP2U1 HCN1 TAF15 MECP2 GRIN1 STUB1 KIF5A TYROBP NT5C2 ERCC5 ACP5 WARS2 OPA1 ARX DNAJC19 SUCLA2 GABRA5 ADAR RAB3GAP1 PEX14 KCNQ2 ALS2 TECR TANGO2 SDHA PEX1 ADD3 TRNK CHMP1A VAMP1 RNASET2 PNKP XPA RAB3GAP2 SDHB ERLIN2 DARS2 KIF1A CNKSR2 FA2H SOX2 UNC80 PET100 ATP2B3 NIPA1 CCDC88C STAMBP SYNJ1 DDHD2 VPS11 CASK TBP GRIN2B NTNG1 ATP6V1A GBA VPS13D LMAN2L XPC PMPCB RTN2 SELENOI GTPBP2 GATAD2B RANBP2 ALS2 GTF2H5 AMACR ND5 STXBP1 CSF1R SYNE1 PDCD1 TUBG1 EIF2S3 BCOR ALDH3A2 COX15 FUS WDR26 PMPCA ERCC4 PARS2 WASHC5 SLC16A2 KDM5C LAGE3 MCCC2 CLTC TCTN2 BSCL2 WWOX SCN3A ATXN8OS SOD1 SURF1 PGAP1 KCNA4 TMEM231 KIDINS220 STXBP1 SLC19A3 CTNNA2 UBA5 KCNA1 TRIT1 CLPB SURF1 L2HGDH MTO1 TRNP TBCD DNMT1 BCS1L RAD50 SPART ITM2B PRUNE1 CASK TUSC3 TPRKB ATP6V1E1 SLC2A1 CDKL5 FAR1 MAG ND2 SDHA L1CAM GLRX5 MECP2 GCDH SURF1 L1CAM IFIH1 GLRX5 CDKL5 SDHD CYP7B1 LINGO1 CLIP2 GPAA1 DHCR24 UBTF SCN1B CLP1 PARS2 FARS2 DEGS1 SERAC1 RAB18 WWOX WDR45B NDUFS2 NIPA1 IFIH1 PPP3CA NSUN2 TBL2 BSCL2 STXBP1 TRMT5 ADAR SIGMAR1 ATP6V1A RARS1 MTFMT GALC ENTPD1 HSD17B10 PPT1 FRRS1L PHGDH SIL1 HACE1 IBA57 FXN FUCA1 SLC39A14 TTC19 AUH PSEN1 MED23 TSEN2 SPTBN2 B4GAT1 DDHD2 ALDH18A1 COASY VCP SPG11 GJC2 AGA CACNA1D NAA10 SACS ATP13A2 ASPA DCPS METTL23 TRAPPC12 BCL11B IBA57 MTPAP DHPS SLC52A2 XPA SNCA CSF1R PCDH12 PEX6 PSAT1 PHACTR1 SPR RSRC1 BSCL2 SLC30A10 HUWE1 SLC25A15 VWA3B THOC2 SCYL1 GAD1 TREM2 PNPLA6 POLR3A GLYCTK RFT1 B4GALNT1 BCOR AP4S1 ARSA OSGEP TACO1 ELOVL4 MRPS22 WASHC4 PFN1 PRDM8 CACNA1G GAN PINK1 MECR FARS2 CAPN1 NDUFA6 USP8 GPAA1 COPB2 CYB5R3 SDHAF1 AARS2 PSAP VPS37A TREM2 ARX ATXN1 ARSI NSD1 HSD17B4 NKX6-2 ANKLE2 TMTC3 CNTNAP1 REEP1 CLIC2 NDUFA13 CIT ISCA1 KLC2 PLP1 SLC1A4 APC TIMM8A GJA1 KIDINS220 PSAT1 RPIA ACER3 SIL1 TBCE C19ORF12 TECPR2 PANK2 CNPY3 TUBB3 CKAP2L ERLIN2 TBCE POLG COX10 KIF1A PHGDH FBXO31 PON3 MTPAP DCX GLE1 LMNB1 WARS2 DARS1 FRRS1L ANK3 AP1S2 PLA2G6 ZC4H2 ALDH18A1 MTHFS HSPD1 SCN2A GRIK2 DYNC1H1 NUP62 HACE1 SLC13A5 ZFYVE26 PRPH BAZ1B NDUFA4 TRNW COA8 ECHS1 AFG3L2 ND6 PRPH GM2A MED25 TARS1 TSEN54 OPA3 TRNV ERCC2 SPAST SPG7 UBA5 ANG SLC2A1 NDUFAF3 MAPK8IP3 ATRX EIF2B2 GDAP2 GBA SIX6 SACS FOXG1 TIMM50 IBA57 PIGQ CCT5 GLT8D1 NADK2 CCDC88C GTF2IRD1 PGAP1 NECAP1 PEX16 PANK2 CRBN POMGNT1 ARG1 NDST1 KRAS SOD1 NDUFS7 MECP2 AUTS2 LYRM7 ARNT2 ZFYVE26 RNF113A ALG11 ARSA AIMP1 MECP2 AP4B1 FOXG1 NAGA ROGDI HPRT1 PIGP NADK2 TP53RK EZH2 CACNA1E CYFIP2 PYCR2 GRIN2D WDR45 MICOS13 ATP6 NEUROD2 MCCC1 HNMT FUCA1 SLC18A2 NPC1 GLB1 NDUFS2 KIF1C KCNT1 CPT1C EIF2B1 KDM5C ATXN3 ABHD12 L2HGDH ALDH3A2 AP4S1 PARK7 IDUA AP4E1 CCNF SDHD DNM1L SLC1A2 WASHC5 SLC2A1 FLNA TARDBP PDHA1 SLC45A1 C19ORF12 AP5Z1 TSEN54 AP1S2 PEX26 PNP MARS2 STXBP1 DARS2 SETBP1 EXOSC3 RETREG1 ADSL SLC2A3 NALCN ARG1 DNAJC6 CYP2U1 ZFYVE27 TUBB4A RAB18 POLR3A PIGN UNC13A NDUFA13 OPHN1 EARS2 RPS6KA3 PEX3 SUZ12 EIF2B5 HMGCL GLRB NDUFA2 AARS1 KY OTUD6B DHDDS GBA2 KIF1A ARX COL4A1 TRNL1 ATXN8OS ASNS TUBB3 TSEN15 VPS13C SPART HEPACAM KATNB1 EIF2B4 HIKESHI SLC19A3 OCLN GM2A CYP7B1 DDX3X PPP1R15B ABCD1 EXOSC9 RTTN CYP27A1 PLA2G6 COG2 NDUFAF6 SOX10 TRNW PLCB1 PEX2 SETBP1 NDE1 ATXN3 DCTN1 RNU4ATAC CHMP2B MCCC2 ATP6AP2 ATP13A2 AFG3L2 SYNE1 TXN2 MED25 STUB1 GNAO1 NDUFA10 SPAST NDUFV2 MLC1 AMPD2 NDUFAF5 LIMK1 NUP62 NDUFV1 ITM2B SLC2A1 BEAN1 SEPSECS SLC35A2 TRNL1 CACNA1A CTNNB1 MCOLN1 TBC1D20 MBOAT7 SPG21 AP4M1 ND1 LIPT1 ATM FDX2 GRIA3 TRNI KCNA1 VCP PEX7 CACNA1D OPA1 ZNF335 SPTAN1 TBK1 SCO2 SLC33A1 SPTBN2 PPP3CA KIF5C CNOT1 NDUFA9 OPA3 RNASEH2C ATAD1 SLC6A8 PRNP PEX16 SZT2 MYO5A DSTYK TPI1 TUFM FRMPD4 ACTL6B SAMHD1 DDB2 PEX19 ELP2 SARS1 TCF20 MECP2 ALS2 AUH GJB1 ATL1 GFM1 KCNB1 MAN2B1 TBC1D23 VPS11 DNMT1 HTRA1 MAG NDUFS4 GCDH IKBKG SAMHD1 NDUFS8 ELOVL4 MOCS2 IARS1