1 Introduction

PhenoExam is an R package and a shiny app that performs:

  • Phenotype and diseases enrichment analysis on a gene set (Phenotype Enrichment Analysis). Using PhenoEnrichGenes function.

  • Measures statistically significant phenotype similarities and detects differential phenotypes between gene sets (Phenotype Comparator). Using RandomComparePheno function.

Phenotypic Similarity between two groups of genes is performed by assessing the statistical significance of the Phenotypic Overlap Ratio (POR) between those (i.e. the number of common enriches phenotypes between the gene sets). Among the gene-phenotype databases within PhenoExam, we find HPO, MGD, and CRISPRbrain. Among the gene-diseases databases within PhenoExam, we find CLINGEN, CTD, CGI, ORPHANET, UNIPROT, PSYGENET and GENOMICS ENGLAND. You can know more about what database or databases are the best choice for your analysis here (Databases within PhenoExamWeb)

In this tutorial, we are going to learn how to install and use PhenoExam. How to do a Phenotype Enrichment Analysis and how compare two genetic diseases with similar symptoms: juvenile Parkinson disease (PD) with 35 genes and early onset dystonia (EOD) with 50 genes from Genomics England PanelApp.

2 How to install PhenoExam

  • If you don’t have devtools package
install.packages("devtools")
library(devtools)
  • To install PhenoExam package you first need some bioconductor packages
if (!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

BiocManager::install("org.Hs.eg.db")
BiocManager::install("clusterProfiler")
BiocManager::install("AnnotationDbi")
  • Install PhenoExam package
install_github("alexcis95/PhenoExam")
library(PhenoExam)
  • The following R packages may be installed during the PhenoExam installation process:

readr, data.table, ggplot2, stats, plotly, ggpubr, dplyr, viridis, parallel, purrr, DT, Hmisc and pheatmap

3 Phenotype Enrichment Analysis

First, we are going to do a phenotype enrichment analysis in Parkinson disease (PD) gene set with 35 genes from Genomics England PanelApp. You can use your own genes. So, we are going to use PhenoEnrichGenes function for this purpose. First, you will need transform the gene symbols in a vector.

# Read file with gene symbols
pdgenes <- fread("Mina/parkinsongenes", header = F)

# get vector with PD genes
pdgenes <- pdgenes$V1

Then we are going to consult the databases that we could use within PhenoExam:

# Read file with gene symbols
getdbnames()
##  [1] "HPO"              "CRB"              "MGD"              "CLINGEN"         
##  [5] "GENOMICS_ENGLAND" "CTD"              "ORPHANET"         "PSYGENET"        
##  [9] "CGI"              "UNIPROT"

Now we can use PhenoEnrichGenes function:

We decided to do the analysis with the PD genes and HPO, MGD, CRB and CTD as databases at the same time. You can do with your genes and selecting the databases that you want.

# Save the db that we want to use in a vector
phedb <- c("HPO", "MGD", "CRB", "CTD")

# Run PhenoEnrichGenes to get the results
parkinsonenrich <- PhenoEnrichGenes(genes= pdgenes, database = phedb)

The results of the analysis is in parkinsonenrich. We have a table that could be interactive and a graph.

# Save the table
tablepark <- parkinsonenrich$htmltabla

# Display the table
 kbl(tablepark[1:25,], escape = F, digits = 1000, align = "c", format = "html", row.names = F) %>%
  kable_material_dark()
term_id term_name source adjust_pvalue genes_associated_in_db gene_overlap overlap_ratio pvalue common_genes
HP:0002067 Bradykinesia HPO 2.164155e-60 97 29 (29/97) 3.565329e-63 PLA2G6, PRKRA, ATP1A3, SYNJ1, LYST, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, RAB39B, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, SLC6A3, VPS35, SNCA, SPR, ATP13A2, TH, SLC39A14, PINK1
HP:0001300 Parkinsonism HPO 2.621777e-51 98 26 (26/98) 4.319238e-54 PLA2G6, PRKRA, ATP1A3, SYNJ1, FBXO7, DNAJC6, DCTN1, C19ORF12, RAB39B, FTL, GBA, GCH1, GRN, WDR45, MAPT, PRKN, PANK2, SLC30A10, SLC6A3, VPS35, SNCA, VPS13A, ATP13A2, TH, SLC39A14, PINK1
HP:0002063 Rigidity HPO 1.976159e-46 144 26 (26/144) 3.255615e-49 PLA2G6, SYNJ1, LYST, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, TUBB4A, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, SLC6A3, VPS35, SNCA, SPR, ATP13A2, TH, PINK1
HP:0001337 Tremor HPO 1.271704e-40 343 28 (28/343) 2.095065e-43 PLA2G6, SYNJ1, LYST, FBXO7, DNAJC6, DCTN1, C19ORF12, TUBB4A, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, OPA3, SPG11, SLC6A3, SNCA, SPR, VPS13A, ATP13A2, TH, SLC39A14, PINK1
HP:0002172 Postural instability HPO 3.861219e-32 59 17 (17/59) 6.361152e-35 PLA2G6, ATP1A3, SYNJ1, FBXO7, CSF1R, DNAJC6, C19ORF12, GBA, PARK7, MAPT, PRKN, LRRK2, SLC30A10, VPS35, SNCA, ATP13A2, PINK1
HP:0000338 Hypomimic face HPO 7.821359e-32 32 15 (15/32) 1.288527e-34 PLA2G6, ATP1A3, SYNJ1, FBXO7, DNAJC6, FTL, GBA, LRRK2, SLC30A10, SLC6A3, VPS35, SNCA, SPR, ATP13A2, SLC39A14
HP:0001332 Dystonia HPO 2.845734e-30 323 23 (23/323) 4.688194e-33 PLA2G6, ATP1A3, SYNJ1, FBXO7, DNAJC6, C19ORF12, TUBB4A, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, VPS35, SNCA, SPR, VPS13A, ATP13A2, PINK1
C0242423 Ramsay Hunt Paralysis Syndrome CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752097 Autosomal Dominant Juvenile Parkinson Disease CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752098 Autosomal Dominant Parkinsonism CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752100 Autosomal Recessive Parkinsonism CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752101 Parkinsonism, Experimental CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752104 Familial Juvenile Parkinsonism CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752105 Parkinsonism, Juvenile CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C1868675 PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE CTD 7.487970e-28 28 13 (13/28) 5.273219e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
HP:0001260 Dysarthria HPO 8.218925e-25 459 22 (22/459) 1.354024e-27 PLA2G6, PRKRA, ATP1A3, SYNJ1, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, RAB39B, TUBB4A, FTL, GBA, MAPT, PANK2, SLC30A10, OPA3, SPG11, SNCA, SPR, VPS13A, ATP13A2
HP:0001347 Hyperreflexia HPO 8.497195e-25 554 23 (23/554) 1.399867e-27 PLA2G6, PRKRA, SYNJ1, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, FTL, GBA, GCH1, GRN, PARK7, MAPT, PRKN, LRRK2, PANK2, OPA3, SPG11, SNCA, SPR, ATP13A2, PINK1
HP:0000726 Dementia HPO 1.386082e-24 150 17 (17/150) 2.283496e-27 FBXO7, DCTN1, C19ORF12, RAB39B, TUBB4A, FTL, GBA, GRN, WDR45, MAPT, LRRK2, PANK2, VPS35, SNCA, VPS13A, ATP13A2, PINK1
HP:0002548 Parkinsonism with favorable response to dopaminergic medication HPO 5.651417e-24 19 11 (11/19) 9.310406e-27 PLA2G6, FBXO7, GBA, GCH1, PARK7, MAPT, LRRK2, VPS35, SNCA, ATP13A2, TH
HP:0000741 Apathy HPO 2.092348e-23 48 13 (13/48) 3.447032e-26 SYNJ1, DNAJC6, DCTN1, GBA, GRN, PARK7, MAPT, PRKN, LRRK2, VPS35, SNCA, ATP13A2, PINK1
HP:0000716 Depressivity HPO 1.158295e-22 313 19 (19/313) 1.908229e-25 PLA2G6, ATP1A3, SYNJ1, CSF1R, DNAJC6, DCTN1, C19ORF12, GBA, GCH1, GRN, PARK7, MAPT, PRKN, LRRK2, PANK2, VPS35, SNCA, ATP13A2, PINK1
HP:0002322 Resting tremor HPO 5.099412e-22 40 12 (12/40) 8.401008e-25 ATP1A3, SYNJ1, DNAJC6, RAB39B, GBA, PARK7, MAPT, LRRK2, OPA3, VPS35, SNCA, PINK1
HP:0001257 Spasticity HPO 6.292195e-22 515 21 (21/515) 1.036605e-24 PLA2G6, SYNJ1, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, TUBB4A, FTL, GBA, PARK7, PRKN, LRRK2, PANK2, OPA3, SPG11, SNCA, SPR, ATP13A2, SLC39A14, PINK1
HP:0002015 Dysphagia HPO 7.397340e-21 311 18 (18/311) 1.218672e-23 PLA2G6, PRKRA, ATP1A3, SYNJ1, FBXO7, C19ORF12, TUBB4A, FTL, GBA, GCH1, MAPT, LRRK2, PANK2, SPG11, VPS35, SNCA, VPS13A, ATP13A2
HP:0100315 Lewy bodies HPO 3.702030e-20 22 10 (10/22) 6.098897e-23 PLA2G6, FBXO7, C19ORF12, RAB39B, GBA, GRN, MAPT, LRRK2, VPS35, SNCA

We observe the interactive table. We get info about the phenotype term id (interactive), term name, the source of the term, a Bonferroni adjust pvalue for enrichment, the number of genes associated with the term in that database (genes_associated_in_db), the number of genes in our gene set that are linked to the term (gene_overlap), the overlap ratio (gene_overlap/genes_associated_in_db), the raw pvalue and the gene symbols of our gene set that linked to the term (interactive).

We can also see on a graph the results:

# Show the graph
parkinsonenrich$graph

Now imagine that you are interesting in getting what are the common genes that are linked to Bradykinesia (HP:0002067) and Lewy bodies (HP:0100315). You can select as many phenotypes terms as you want. You can use findoverlapgenes function.

# set phenotypes in a vector
phenosover <- c("HP:0002067", "HP:0100315")


# get common genes
prueba <- findoverlapgenes(phenosover)

# show
prueba
##  [1] "ADH1C"    "ATXN2"    "ATXN8OS"  "C19ORF12" "DNAJC13"  "EIF4G1"  
##  [7] "FBXO7"    "GBA"      "GIGYF2"   "GLUD2"    "LRRK2"    "MAPT"    
## [13] "NR4A2"    "PLA2G6"   "RAB39B"   "SNCA"     "SNCAIP"   "TBP"     
## [19] "VPS13C"   "VPS35"

4 Comparator Phenotype analysis

PhenoExam can compare the phenotype analysis of two gene sets in order to determine the similarity of phenotypes and find the phenotypic differences that make each gene set unique. In this case we are going to compare between Parkinson genes and Dystonia genes. Two diseases with similar symptoms. First we are going to obtain dystonia genes.

# Read file with gene symbols
dysgenes <- fread("Mina/dystoniagenes", header = F)

# get vector with Dystonia genes
dysgenes <- dysgenes$V1


# Read file with gene symbols
pdgenes <- fread("Mina/parkinsongenes", header = F)

# get vector with PD genes
pdgenes <- pdgenes$V1

We use RandomComparePheno function.

We decided to do the analysis with the PD genes and Dystonia genes and HPO, MGD, CRB and CTD as databases at the same time. We also have to define the number of random test to calculate the scores (nulltestnumber = 50 in our case). You can do with your genes and selecting the databases that you want.

# Save the db that we want to use in a vector
phedb <- c("HPO", "MGD", "CRB", "CTD")

# Run the anaysis
comparareparkdis <- RandomComparePheno(geneset = pdgenes, genesetcompare = dysgenes, database = phedb, nulltestnumber = 50)

First, we get a message with the summary of the analysis:

comparareparkdis$phenomessage
## [1] "Gene set2 and gene set1 shared 1102 phenotypic terms (out of 2313 unique phenotypic terms in both), that yields a Relaxed Phenotypic Overlap Ratio (RPOR) of 0.476 (p < 0.019608). They shared 139 significant phenotypic terms (out of 273 unique significant phenotypic terms in both), that yields a Phenotypic Overlap Ratio (POR) of 0.509 (p < 0.019608). Phenotype relevance association analysis for gene sets (i.e. whether the shared phenotypes are similar in relevance, i.e. in the number of genes associated with them, within each gene set) results in an adjusted R squared of 0.643 ( p < 9.23412724265217e-63) which suggests that an important portion of the common phenotypes are similar in relevance.  The p-values were obtained through randomization of 50 random gene sets.  Gene set 1 and gene set 2 are statistically significantly similar to each other in phenotypic terms."

Once the enrichment phenotypes of a gene set have been determined (i.e phenotypes with p < 0.05 in each gene set), it may be useful to calculate the number of these phenotypes shared between two gene sets (G and G’) to know what ratio of phenotypic terms those gene sets share.

In addition to calculating which enrichment phenotypes share two gene sets, we will be interested in determining whether this is due to the random chance. We can determine whether the Phenotypic Overlap Ratio (POR) is statistically significant by using randomization. To answer the question of whether the phenotypic overlap between G and G’ is significant. i.e. for G and G’, POR (G,G’) is compared with the POR of a random gene set POR (G,R) and POR (G’,R), where R has the same number of genes as G’ or G respectively, all genes are selected at random and all are protein coding. We can calculate the POR for different random gene sets (R1,R2,…,Rm). We can now check how many random gene sets have a higher POR than our test, if the number of higher POR of these random gene sets is less than 5% of the total then p < 0.05 and we could conclude that the number of phenotypes shared between these two gene sets is statistically significant.

Parkinson genes and Dystonia genes get a Phenotypic Overlap Ratio (POR) of 0.511 (p < 0.019608). We get a plot with the 50 randomization values of the POR score:

comparareparkdis$POR

Not this time but sometimes POR is too demanding and valuable information cannot be obtained. In these cases it is useful Relaxed Phenotypic Overlap Ratio (RPOR). RPOR is calculated in a similar way to the POR but with all phenotypes, whether these are enriched or not.

comparareparkdis$RPOR

We can measure the linear regression with the adjusted R square and if it is significant with the pvalue of the regression. If there is no linear relationship there is no consistent pattern of association of phenotypic relevance.

Besides measuring the phenotypic similarities between the two gene sets we can also see in which phenotypes are not similar, that is, which phenotypes make that gene set unique with respect to the other.

We get an interactive plot with the relevant phenotypic terms for each gene set:

comparareparkdis$plotdif

For example, significant only in PD phenotypes include Astrocytosis (MP:0003354), Substantia nigra gliosis (HP:0011960), Neuronal loss in central nervous system (HP:0002529) and Orthostatic hypotension due to autonomic dysfunction (HP:0004926).

  kbl(comparareparkdis$tabledif1, escape = F, digits = 1000, align = "c", format = "html", row.names = F) %>%
  kable_material_dark()
term_id term_name source adjust_pvalue_set1 gene_overlap_set1 overlap_ratio_set1 pvalue_set1 common_genes_set1 adjust_pvalue_set2 gene_overlap_set2 overlap_ratio_set2 pvalue_set2 common_genes_set2
MP:0003354 astrocytosis MGD 5.167872e-12 11 (11/159) 6.668222e-15 ATP13A2, ATP1A3, DCTN1, GBA, GRN, LRRK2, MAPT, SNCA, SPG11, TUBB4A, WDR45 0.06406219 5 (5/159) 7.977857e-05 ATP13A2, ATP1A3, TUBB4A, VAC14, WDR45
HP:0011960 Substantia nigra gliosis HPO 4.149266e-11 6 (6/14) 6.835693e-14 FBXO7, GBA, MAPT, PRKN, LRRK2, SNCA 0.45659961 2 (2/14) 5.899220e-04 FBXO7, PRKN
HP:0002171 Gliosis HPO 2.675056e-10 8 (8/70) 4.407012e-13 PLA2G6, CSF1R, GBA, GRN, MAPT, LRRK2, VPS35, SNCA 1.00000000 2 (2/70) 1.427164e-02 PLA2G6, YY1
HP:0002367 Visual hallucinations HPO 3.724691e-10 6 (6/19) 6.136229e-13 FBXO7, GBA, LRRK2, VPS35, SNCA, ATP13A2 0.85091344 2 (2/19) 1.099371e-03 FBXO7, ATP13A2
MP:0008918 microgliosis MGD 2.260114e-09 8 (8/82) 2.916277e-12 ATP1A3, CSF1R, DCTN1, GRN, LRRK2, MAPT, SLC6A3, VPS35 1.00000000 2 (2/82) 2.204245e-02 ATP1A3, SLC6A3
HP:0003677 Slow progression HPO 7.504334e-09 9 (9/166) 1.236299e-11 FBXO7, DNAJC6, DCTN1, C19ORF12, PARK7, LRRK2, PANK2, SPG11, PINK1 0.05382785 5 (5/166) 6.954502e-05 FBXO7, C19ORF12, HPCA, PANK2, PINK1
HP:0007311 Short stepped shuffling gait HPO 3.855944e-08 5 (5/16) 6.352462e-11 SYNJ1, DNAJC6, DCTN1, GBA, MAPT 1.00000000 1 (1/16) 4.077833e-02 SYNJ1
HP:0001621 Weak voice HPO 1.361549e-07 5 (5/20) 2.243079e-10 SYNJ1, DNAJC6, DCTN1, GBA, MAPT 1.00000000 1 (1/20) 5.071553e-02 SYNJ1
HP:0002359 Frequent falls HPO 1.653869e-07 7 (7/92) 2.724660e-10 C19ORF12, GBA, MAPT, LRRK2, PANK2, VPS35, SNCA 0.07363034 4 (4/92) 9.512964e-05 ADAR, C19ORF12, FA2H, PANK2
HP:0002366 Abnormal lower motor neuron morphology HPO 2.943525e-07 5 (5/23) 4.849300e-10 DCTN1, C19ORF12, GRN, MAPT, SPG11 1.00000000 2 (2/23) 1.615798e-03 CHMP2B, C19ORF12
MP:0002083 premature death MGD 9.267314e-07 17 (17/1591) 1.195783e-09 ATP1A3, CSF1R, GBA, GRN, LYST, MAPT, OPA3, PINK1, PLA2G6, PRKN, PRKRA, SLC30A10, SLC6A3, SNCA, SPR, TH, TUBB4A 0.06398095 14 (14/1591) 7.967739e-05 ATM, ATP1A3, GNAO1, HTRA2, PINK1, PLA2G6, PRKN, PRKRA, SLC30A10, SLC6A3, SPR, TH, TOR1A, TUBB4A
HP:0005340 Spastic/hyperactive bladder HPO 1.158382e-06 4 (4/10) 1.908372e-09 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
HP:0003581 Adult onset HPO 2.004468e-06 7 (7/131) 3.302254e-09 CSF1R, DCTN1, GBA, PARK7, MAPT, PRKN, SPG11 0.28663212 4 (4/131) 3.703257e-04 CP, CHMP2B, PRKN, APTX
MP:0001262 decreased body weight MGD 3.632875e-06 17 (17/1739) 4.687580e-09 ATP1A3, CSF1R, DNAJC6, GBA, GRN, MAPT, OPA3, PANK2, PINK1, PRKN, PRKRA, SLC30A10, SLC39A14, SLC6A3, SNCA, SPR, TH 0.16567417 14 (14/1739) 2.063190e-04 ATM, ATP1A3, ATP7B, GNAO1, HTRA2, PANK2, PINK1, PRKN, PRKRA, SLC30A10, SLC6A3, SPR, TH, TOR1A
HP:0000012 Urinary urgency HPO 3.744327e-06 5 (5/37) 6.168579e-09 GBA, MAPT, SPG11, SNCA, PINK1 1.00000000 2 (2/37) 4.155953e-03 FA2H, PINK1
HP:0002529 Neuronal loss in central nervous system HPO 3.744327e-06 5 (5/37) 6.168579e-09 PLA2G6, CSF1R, GBA, GRN, MAPT 0.09320640 3 (3/37) 1.204217e-04 PLA2G6, CHMP2B, VAC14
HP:0031908 Micrographia HPO 5.493213e-06 4 (4/14) 9.049774e-09 FTL, GBA, MAPT, SNCA 1.00000000 1 (1/14) 3.577157e-02 FTL
HP:0002375 Hypokinesia HPO 6.403886e-06 5 (5/41) 1.055006e-08 GBA, SLC6A3, SNCA, ATP13A2, TH 0.12694231 3 (3/41) 1.640082e-04 SLC6A3, ATP13A2, TH
HP:0002300 Mutism HPO 7.259829e-06 5 (5/42) 1.196018e-08 ATP1A3, CSF1R, FTL, GRN, MAPT 0.13645749 3 (3/42) 1.763017e-04 ATP1A3, CHMP2B, FTL
HP:0002120 Cerebral cortical atrophy HPO 7.406272e-06 8 (8/249) 1.220144e-08 GBA, GRN, LRRK2, SPG11, VPS35, SNCA, VPS13A, ATP13A2 0.35498487 5 (5/249) 4.586368e-04 CHMP2B, BCAP31, FA2H, VPS13A, ATP13A2
HP:0000744 Low frustration tolerance HPO 7.481093e-06 4 (4/15) 1.232470e-08 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
HP:0004926 Orthostatic hypotension due to autonomic dysfunction HPO 9.961937e-06 4 (4/16) 1.641176e-08 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
MP:0004250 tau protein deposits MGD 1.277138e-05 4 (4/15) 1.647920e-08 GRN, LRRK2, MAPT, PRKN 1.00000000 1 (1/15) 4.111704e-02 PRKN
MP:0002882 abnormal neuron morphology MGD 1.842608e-05 7 (7/162) 2.377559e-08 ATP13A2, GBA, LRRK2, MAPT, PRKN, SLC6A3, SPG11 0.06998084 5 (5/162) 8.714925e-05 ATP13A2, CP, PRKN, SLC6A3, TOR1A
MP:0005405 axon degeneration MGD 2.257746e-05 6 (6/96) 2.913220e-08 OPA3, PLA2G6, SNCA, SPG11, TUBB4A, WDR45 0.11904719 4 (4/96) 1.482530e-04 NKX6-2, PLA2G6, TUBB4A, WDR45
MP:0001473 reduced long term potentiation MGD 3.137726e-05 7 (7/175) 4.048679e-08 GRN, MAPT, PINK1, SLC6A3, SNCA, VPS35, WDR45 1.00000000 3 (3/175) 1.287093e-02 PINK1, SLC6A3, WDR45
HP:0002145 Frontotemporal dementia HPO 3.254893e-05 4 (4/21) 5.362263e-08 PLA2G6, DCTN1, GRN, MAPT 1.00000000 2 (2/21) 1.345633e-03 PLA2G6, CHMP2B
HP:0001824 Weight loss HPO 5.075602e-05 7 (7/209) 8.361782e-08 DCTN1, GBA, LRRK2, PANK2, VPS35, SNCA, VPS13A 1.00000000 4 (4/209) 2.104805e-03 ATM, ATP7B, PANK2, VPS13A
HP:0002014 Diarrhea HPO 6.157985e-05 7 (7/215) 1.014495e-07 SYNJ1, DNAJC6, PARK7, PRKN, LRRK2, SNCA, PINK1 1.00000000 4 (4/215) 2.332318e-03 SYNJ1, HTRA2, PRKN, PINK1
HP:0002465 Poor speech HPO 6.356087e-05 7 (7/216) 1.047131e-07 CSF1R, RAB39B, TUBB4A, GRN, WDR45, MAPT, SLC39A14 0.18477524 5 (5/216) 2.387277e-04 CHMP2B, DLAT, TUBB4A, WDR45, WDR73
MP:0008842 lipofuscinosis MGD 6.778025e-05 4 (4/22) 8.745838e-08 ATP13A2, GBA, GRN, LRRK2 1.00000000 1 (1/22) 5.973349e-02 ATP13A2
HP:0000514 Slow saccadic eye movements HPO 8.078192e-05 4 (4/26) 1.330839e-07 FBXO7, MAPT, SNCA, ATP13A2 1.00000000 2 (2/26) 2.065333e-03 FBXO7, ATP13A2
MP:0004077 abnormal striatum morphology MGD 8.324571e-05 5 (5/60) 1.074138e-07 GBA, LRRK2, PARK7, SLC6A3, SNCA 1.00000000 1 (1/60) 1.547789e-01 SLC6A3
HP:0000505 Visual impairment HPO 9.000025e-05 8 (8/344) 1.482706e-07 PLA2G6, SYNJ1, LYST, CSF1R, TUBB4A, GRN, OPA3, SPG11 1.00000000 4 (4/344) 1.210311e-02 PLA2G6, SYNJ1, MECR, TUBB4A
MP:0001463 abnormal spatial learning MGD 9.913875e-05 7 (7/207) 1.279210e-07 ATP13A2, ATP1A3, GRN, MAPT, PRKN, SLC6A3, VPS35 0.21993112 5 (5/207) 2.738868e-04 ATP13A2, ATP1A3, FA2H, PRKN, SLC6A3
MP:0010069 increased serotonin level MGD 1.881477e-04 4 (4/28) 2.427713e-07 PARK7, PRKN, SLC6A3, TH 0.05139906 3 (3/28) 6.400880e-05 PRKN, SLC6A3, TH
HP:0012450 Chronic constipation HPO 2.480203e-04 4 (4/34) 4.086001e-07 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
MP:0001263 weight loss MGD 2.700510e-04 8 (8/358) 3.484529e-07 LYST, PARK7, PLA2G6, SLC6A3, SNCA, SPG11, TH, TUBB4A 1.00000000 5 (5/358) 3.156075e-03 PLA2G6, SLC6A3, TH, TOR1A, TUBB4A
MP:0003172 abnormal lysosome physiology MGD 3.286138e-04 4 (4/32) 4.240178e-07 ATP13A2, LYST, SLC6A3, SPG11 1.00000000 2 (2/32) 3.597070e-03 ATP13A2, SLC6A3
HP:0000511 Vertical supranuclear gaze palsy HPO 3.976936e-04 3 (3/10) 6.551789e-07 DCTN1, MAPT, ATP13A2 1.00000000 1 (1/10) 2.568110e-02 ATP13A2
MP:0002797 increased thigmotaxis MGD 4.285353e-04 5 (5/83) 5.529488e-07 ATP1A3, GRN, PRKN, SLC6A3, TH 0.06763386 4 (4/83) 8.422647e-05 ATP1A3, PRKN, SLC6A3, TH
MP:0003633 abnormal nervous system physiology MGD 4.384678e-04 6 (6/158) 5.657649e-07 GRN, MAPT, PINK1, SLC6A3, SNCA, TH 0.06217769 5 (5/158) 7.743175e-05 CSTB, GNAO1, PINK1, SLC6A3, TH
MP:0005404 abnormal axon morphology MGD 8.528080e-04 6 (6/177) 1.100397e-06 LRRK2, MAPT, PLA2G6, SLC6A3, SNCA, TUBB4A 0.10615682 5 (5/177) 1.322003e-04 FA2H, PLA2G6, SLC6A3, TUBB4A, XK
HP:0000719 Inappropriate behavior HPO 9.442960e-04 3 (3/13) 1.555677e-06 DCTN1, GRN, MAPT 1.00000000 1 (1/13) 3.325859e-02 CHMP2B
HP:0006892 Frontotemporal cerebral atrophy HPO 9.442960e-04 3 (3/13) 1.555677e-06 PLA2G6, GRN, MAPT 0.39202168 2 (2/13) 5.064880e-04 PLA2G6, CHMP2B
HP:0008969 Leg muscle stiffness HPO 9.442960e-04 3 (3/13) 1.555677e-06 SYNJ1, DNAJC6, ATP13A2 0.39202168 2 (2/13) 5.064880e-04 SYNJ1, ATP13A2
MP:0001906 increased dopamine level MGD 1.008767e-03 4 (4/42) 1.301634e-06 PARK7, PRKN, SLC6A3, SNCA 1.00000000 2 (2/42) 6.134030e-03 PRKN, SLC6A3
C0752347 Lewy Body Disease CTD 1.108378e-03 3 (3/22) 7.805477e-06 GBA, SNCA, TH 1.00000000 1 (1/22) 5.457532e-02 TH
MP:0013219 abnormal substantia nigra pars compacta morphology MGD 1.498919e-03 3 (3/13) 1.934089e-06 PARK7, PRKN, SLC6A3 0.46988718 2 (2/13) 5.851646e-04 PRKN, SLC6A3
HP:0002186 Apraxia HPO 1.909359e-03 4 (4/56) 3.145566e-06 PLA2G6, CSF1R, GRN, MAPT 0.32117645 3 (3/56) 4.149567e-04 PLA2G6, CHMP2B, SLC2A1
HP:0002380 Fasciculations HPO 2.199892e-03 4 (4/58) 3.624204e-06 DCTN1, GRN, MAPT, SPG11 1.00000000 1 (1/58) 1.402255e-01 CHMP2B
MP:0011451 increased susceptibility to dopaminergic neuron neurotoxicity MGD 2.378253e-03 3 (3/15) 3.068714e-06 GRN, PARK7, SLC6A3 1.00000000 1 (1/15) 4.111704e-02 SLC6A3
C0751263 Learning Disturbance CTD 2.607477e-03 3 (3/29) 1.836251e-05 MAPT, PRKN, TH 0.62219049 2 (2/29) 2.469010e-03 PRKN, TH
C0751265 Learning Disabilities CTD 2.607477e-03 3 (3/29) 1.836251e-05 MAPT, PRKN, TH 0.62219049 2 (2/29) 2.469010e-03 PRKN, TH
HP:0003587 Insidious onset HPO 2.677466e-03 3 (3/18) 4.410982e-06 GBA, MAPT, SNCA 1.00000000 0 1 1.000000e+00 1
HP:0100753 Schizophrenia HPO 3.479008e-03 4 (4/65) 5.731480e-06 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
MP:0005059 lysosomal protein accumulation MGD 3.544789e-03 3 (3/17) 4.573921e-06 ATP13A2, DCTN1, LYST 1.00000000 1 (1/17) 4.647257e-02 ATP13A2
MP:0010149 abnormal synaptic dopamine release MGD 3.544789e-03 3 (3/17) 4.573921e-06 LRRK2, SLC6A3, SNCA 1.00000000 1 (1/17) 4.647257e-02 SLC6A3
HP:0002185 Neurofibrillary tangles HPO 4.347711e-03 3 (3/21) 7.162622e-06 PLA2G6, GRN, MAPT 1.00000000 1 (1/21) 5.318403e-02 PLA2G6
HP:0000011 Neurogenic bladder HPO 5.774902e-03 3 (3/23) 9.513841e-06 FBXO7, SNCA, ATP13A2 1.00000000 2 (2/23) 1.615798e-03 FBXO7, ATP13A2
MP:0010047 axonal spheroids MGD 6.896090e-03 3 (3/21) 8.898181e-06 CSF1R, PLA2G6, WDR45 1.00000000 2 (2/21) 1.553103e-03 PLA2G6, WDR45
MP:0000160 kyphosis MGD 7.021403e-03 6 (6/255) 9.059875e-06 GBA, PINK1, PLA2G6, PRKN, SLC6A3, SNCA 1.00000000 4 (4/255) 5.548724e-03 PINK1, PLA2G6, PRKN, SLC6A3
C0025261 Memory Disorders CTD 8.657155e-03 3 (3/43) 6.096588e-05 MAPT, PRKN, SLC6A3 1.00000000 2 (2/43) 5.368125e-03 PRKN, SLC6A3
MP:0003461 abnormal response to novel object MGD 8.894255e-03 4 (4/72) 1.147646e-05 ATP13A2, ATP1A3, GRN, SLC6A3 0.85826274 3 (3/72) 1.068820e-03 ATP13A2, ATP1A3, SLC6A3
MP:0000753 paralysis MGD 9.920034e-03 4 (4/74) 1.280004e-05 ATP1A3, DCTN1, GBA, PRKRA 0.92921499 3 (3/74) 1.157179e-03 ATP1A3, HTRA2, PRKRA
HP:0000709 Psychosis HPO 1.062070e-02 4 (4/86) 1.749704e-05 GRN, MAPT, PANK2, VPS13A 0.05660324 4 (4/86) 7.313081e-05 CHMP2B, PANK2, DCAF17, VPS13A
MP:0008260 abnormal autophagy MGD 1.103045e-02 4 (4/76) 1.423284e-05 LRRK2, PRKN, SLC6A3, SPG11 1.00000000 2 (2/76) 1.911761e-02 PRKN, SLC6A3
MP:0001905 abnormal dopamine level MGD 1.186177e-02 3 (3/25) 1.530551e-05 LRRK2, PARK7, PRKN 1.00000000 2 (2/25) 2.202948e-03 PNKD, PRKN
MP:0011448 decreased dopaminergic neuron number MGD 1.186177e-02 3 (3/25) 1.530551e-05 PRKN, SLC6A3, SNCA 1.00000000 2 (2/25) 2.202948e-03 PRKN, SLC6A3
MP:0004811 abnormal neuron physiology MGD 1.416199e-02 5 (5/169) 1.827354e-05 ATP1A3, GRN, PINK1, SLC6A3, SNCA 1.00000000 4 (4/169) 1.260374e-03 ATP1A3, PINK1, SLC6A3, TOR1A
HP:0002344 Progressive neurologic deterioration HPO 1.451191e-02 3 (3/31) 2.390759e-05 SYNJ1, GBA, GCH1 1.00000000 2 (2/31) 2.930638e-03 SYNJ1, GCH1
C3160718 PARKINSON DISEASE, LATE-ONSET CTD 1.565477e-02 2 (2/9) 1.102448e-04 GBA, MAPT 1.00000000 0 1 1.000000e+00 1
HP:0002483 Bulbar signs HPO 1.599319e-02 3 (3/32) 2.634793e-05 GBA, SPG11, SLC39A14 1.00000000 1 (1/32) 7.992571e-02 CHMP2B
MP:0001399 hyperactivity MGD 1.793752e-02 8 (8/631) 2.314519e-05 ATP1A3, LRRK2, MAPT, PLA2G6, SLC6A3, SNCA, TH, WDR45 0.26618898 8 (8/631) 3.314931e-04 ATP1A3, CSTB, GNAO1, PLA2G6, SLC6A3, TH, TOR1A, WDR45
MP:0009454 impaired contextual conditioning behavior MGD 2.451814e-02 4 (4/93) 3.163631e-05 ATP1A3, GRN, MAPT, WDR45 1.00000000 2 (2/93) 2.784945e-02 ATP1A3, WDR45
MP:0004768 abnormal axonal transport MGD 2.534121e-02 3 (3/32) 3.269833e-05 MAPT, PRKN, SLC6A3 1.00000000 2 (2/32) 3.597070e-03 PRKN, SLC6A3
HP:0002354 Memory impairment HPO 2.701166e-02 4 (4/109) 4.450026e-05 CSF1R, GRN, MAPT, VPS13A 0.14192397 4 (4/109) 1.833643e-04 CP, CHMP2B, PRRT2, VPS13A
MP:0008571 abnormal synaptic bouton morphology MGD 2.783798e-02 3 (3/33) 3.591998e-05 MAPT, PLA2G6, SLC6A3 1.00000000 2 (2/33) 3.822329e-03 PLA2G6, SLC6A3
C0030569 Secondary Parkinson Disease CTD 2.860412e-02 2 (2/12) 2.014374e-04 PRKN, ATP13A2 0.10397955 2 (2/12) 4.126172e-04 PRKN, ATP13A2
C0751414 Parkinson Disease, Secondary Vascular CTD 2.860412e-02 2 (2/12) 2.014374e-04 PRKN, ATP13A2 0.10397955 2 (2/12) 4.126172e-04 PRKN, ATP13A2
C0751415 Atherosclerotic Parkinsonism CTD 2.860412e-02 2 (2/12) 2.014374e-04 PRKN, ATP13A2 0.10397955 2 (2/12) 4.126172e-04 PRKN, ATP13A2
MP:0002062 abnormal associative learning MGD 3.330495e-02 3 (3/35) 4.297413e-05 MAPT, SLC6A3, TH 1.00000000 2 (2/35) 4.292055e-03 SLC6A3, TH
HP:0010526 Dysgraphia HPO 3.398914e-02 3 (3/41) 5.599528e-05 GRN, MAPT, VPS13A 1.00000000 2 (2/41) 5.083204e-03 CHMP2B, VPS13A
HP:0000666 Horizontal nystagmus HPO 3.655811e-02 3 (3/42) 6.022753e-05 GBA, GCH1, ATP13A2 0.13645749 3 (3/42) 1.763017e-04 GCH1, FA2H, ATP13A2
MP:0001732 postnatal growth retardation MGD 3.769868e-02 9 (9/915) 4.864345e-05 CSF1R, MAPT, OPA3, PANK2, PRKRA, SLC39A14, SLC6A3, SPR, SYNJ1 1.00000000 8 (8/915) 3.599002e-03 ATM, ATP7B, HTRA2, PANK2, PRKRA, SLC6A3, SPR, SYNJ1
HP:0002518 Abnormality of the periventricular white matter HPO 3.925104e-02 3 (3/43) 6.466399e-05 CSF1R, SPG11, ATP13A2 1.00000000 2 (2/43) 5.579251e-03 FA2H, ATP13A2
C0013386 Dyskinesia, Drug-Induced CTD 4.535392e-02 2 (2/15) 3.193938e-04 GCH1, TH 0.16461597 2 (2/15) 6.532380e-04 GCH1, TH

On the other hand, we found significant only phenotypes in EOD such as Writer’s cramp (HP:0002356), Hypoplasia of the corpus callosum (HP:0002079), Acanthocytosis (HP:0001927), Microcephaly (HP:0000252), Intellectual disability, mild (HP:0001256) and Hyperactive deep tendon reflexes (HP:0006801).

  kbl(comparareparkdis$tabledif2, escape = F, digits = 1000, align = "c", format = "html", row.names = F) %>%
  kable_material_dark()
term_id term_name source adjust_pvalue_set1 gene_overlap_set1 overlap_ratio_set1 pvalue_set1 common_genes_set1 adjust_pvalue_set2 gene_overlap_set2 overlap_ratio_set2 pvalue_set2 common_genes_set2
HP:0002356 Writer’s cramp HPO 0.23026017 2 (2/16) 3.793413e-04 FTL, GCH1 1.368500e-09 6 (6/16) 1.768087e-12 SGCE, TOR1A, FTL, GCH1, PRRT2, THAP1
HP:0002355 Difficulty walking HPO 0.49533007 4 (4/233) 8.160298e-04 SYNJ1, C19ORF12, SLC30A10, ATP13A2 1.232727e-08 11 (11/233) 1.592670e-11 ADAR, ADCY5, ATP7B, SYNJ1, C19ORF12, NKX6-2, HPCA, FA2H, SLC30A10, COASY, ATP13A2
C0393598 Idiopathic familial dystonia CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0743332 Focal Dystonia CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752197 Adult-Onset Dystonias CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752198 Adult-Onset Idiopathic Focal Dystonias CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752199 Adult-Onset Idiopathic Torsion Dystonias CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752200 Autosomal Dominant Familial Dystonia CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752201 Autosomal Recessive Familial Dystonia CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752202 Childhood Onset Dystonias CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752203 Dystonia, Primary CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752205 Dystonia, Secondary CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752206 Dystonias, Sporadic CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752207 Familial Dystonia CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C0752208 Pseudodystonia CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
C4316810 Writer’s Cramp CTD 1.00000000 1 (1/7) 1.241245e-02 PRKRA 3.261744e-07 4 (4/7) 1.294343e-09 TOR1A, PRKRA, KMT2B, THAP1
HP:0003593 Infantile onset HPO 0.08134444 6 (6/444) 1.340106e-04 PLA2G6, GCH1, SLC6A3, SPR, TH, PINK1 8.319794e-07 12 (12/444) 1.074909e-09 ADAR, PLA2G6, PNKD, DLAT, NKX6-2, GCH1, WDR73, SLC2A1, SLC6A3, SPR, TH, PINK1
HP:0003829 Incomplete penetrance HPO 1.00000000 2 (2/147) 2.923934e-02 ATP1A3, LRRK2 3.027666e-06 8 (8/147) 3.911713e-09 ATP1A3, SGCE, KMT2B, TOR1A, PRRT2, THAP1, SLC2A1, ANO3
HP:0002487 Hyperkinetic movements HPO 0.61654294 2 (2/26) 1.015721e-03 GCH1, SLC6A3 4.705514e-06 5 (5/26) 6.079476e-09 PNKD, GCH1, GNAO1, PRRT2, SLC6A3
HP:0000722 Obsessive-compulsive behavior HPO 1.00000000 2 (2/61) 5.495815e-03 GCH1, PANK2 8.686896e-06 6 (6/61) 1.122338e-08 SGCE, TOR1A, GCH1, PANK2, COASY, XK
HP:0002079 Hypoplasia of the corpus callosum HPO 1.00000000 3 (3/385) 3.240602e-02 SYNJ1, SPG11, ATP13A2 3.556739e-05 10 (10/385) 4.595270e-08 ADAR, SYNJ1, NKX6-2, GNAO1, HTRA2, WDR73, FA2H, COASY, ATP13A2, YY1
HP:0002059 Cerebral atrophy HPO 0.12320539 5 (5/302) 2.029743e-04 PLA2G6, SYNJ1, GBA, WDR45, SLC39A14 5.642872e-05 9 (9/302) 7.290532e-08 PLA2G6, SYNJ1, BCAP31, NKX6-2, GNAO1, HTRA2, WDR45, WDR73, SLC2A1
HP:0001270 Motor delay HPO 0.06080187 6 (6/421) 1.001678e-04 PRKRA, ATP1A3, TUBB4A, GBA, SPR, TH 8.198510e-05 10 (10/421) 1.059239e-07 ADCY5, PRKRA, ATP1A3, KMT2B, MECR, TUBB4A, NKX6-2, WDR73, SPR, TH
HP:0000252 Microcephaly HPO 1.00000000 5 (5/939) 2.633182e-02 SYNJ1, TUBB4A, GBA, SLC30A10, SPR 4.167811e-04 13 (13/939) 5.384769e-07 ADAR, SYNJ1, KMT2B, DLAT, BCAP31, TUBB4A, GNAO1, WDR73, SERAC1, SLC30A10, SLC2A1, COASY, SPR
MP:0002183 gliosis MGD 0.05824165 4 (4/116) 7.515052e-05 ATP13A2, SNCA, TH, VPS13A 6.586710e-04 6 (6/116) 8.202628e-07 ATP13A2, HTRA2, TH, TOR1A, VAC14, VPS13A
HP:0011968 Feeding difficulties HPO 0.09184094 6 (6/454) 1.513030e-04 PLA2G6, SYNJ1, GBA, SLC6A3, VPS13A, TH 1.716224e-03 9 (9/454) 2.217343e-06 PLA2G6, SYNJ1, WDR73, SERAC1, HPCA, SLC6A3, VPS13A, TH, YY1
MP:0003908 decreased stereotypic behavior MGD 0.12833623 2 (2/10) 1.655951e-04 PINK1, TH 1.950689e-03 3 (3/10) 2.429252e-06 PINK1, SGCE, TH
HP:0002307 Drooling HPO 0.34109807 3 (3/89) 5.619408e-04 ATP1A3, RAB39B, VPS13A 2.626055e-03 5 (5/89) 3.392836e-06 ATP1A3, ATP7B, DLAT, VAC14, VPS13A
HP:0001927 Acanthocytosis HPO 0.12722312 2 (2/12) 2.095933e-04 PANK2, VPS13A 2.762602e-03 3 (3/12) 3.569253e-06 PANK2, VPS13A, XK
HP:0003621 Juvenile onset HPO 1.00000000 2 (2/94) 1.264447e-02 PANK2, SPG11 3.439108e-03 5 (5/94) 4.443292e-06 ADCY5, SGCE, HPCA, APTX, PANK2
HP:0045084 Limb myoclonus HPO 1.00000000 1 (1/14) 2.516688e-02 MAPT 4.554134e-03 3 (3/14) 5.883895e-06 SGCE, TOR1A, SLC2A1
HP:0012075 Personality disorder HPO 1.00000000 0 1 1.000000e+00 1 4.554134e-03 3 (3/14) 5.883895e-06 SGCE, TOR1A, XK
HP:0001256 Intellectual disability, mild HPO 1.00000000 1 (1/271) 3.914781e-01 TH 4.677822e-03 7 (7/271) 6.043698e-06 ADAR, DLAT, PRRT2, DCAF17, SLC2A1, TH, YY1
HP:0002061 Lower limb spasticity HPO 1.00000000 2 (2/48) 3.438049e-03 FBXO7, SPG11 5.576861e-03 4 (4/48) 7.205247e-06 FBXO7, FA2H, PRRT2, SLC2A1
HP:0002078 Truncal ataxia HPO 1.00000000 2 (2/48) 3.438049e-03 ATP1A3, SLC30A10 5.576861e-03 4 (4/48) 7.205247e-06 ATP1A3, NKX6-2, APTX, SLC30A10
HP:0025401 Staring gaze HPO 1.00000000 1 (1/15) 2.694078e-02 SYNJ1 5.682250e-03 3 (3/15) 7.341409e-06 SYNJ1, PNKD, PRRT2
C0020796 Profound Mental Retardation CTD 0.27332602 3 (3/139) 1.924831e-03 TH, PRKRA, RAB39B 6.835074e-03 5 (5/139) 2.712331e-05 SLC2A1, TH, YY1, PRKRA, PRRT2
C0917816 Mental deficiency CTD 0.27332602 3 (3/139) 1.924831e-03 TH, PRKRA, RAB39B 6.835074e-03 5 (5/139) 2.712331e-05 SLC2A1, TH, YY1, PRKRA, PRRT2
HP:0000486 Strabismus HPO 1.00000000 5 (5/696) 8.050861e-03 PLA2G6, LYST, RAB39B, GBA, ATP13A2 7.688084e-03 10 (10/696) 9.932925e-06 PLA2G6, ATM, BCAP31, NKX6-2, GNAO1, WDR73, FA2H, SLC2A1, ATP13A2, YY1
MP:0001409 increased stereotypic behavior MGD 1.00000000 2 (2/51) 4.461779e-03 SLC6A3, TH 9.822370e-03 4 (4/51) 1.223209e-05 HTRA2, SLC6A3, TH, TOR1A
HP:0003324 Generalized muscle weakness HPO 0.77333113 3 (3/118) 1.274022e-03 PLA2G6, DCTN1, ATP13A2 1.046131e-02 5 (5/118) 1.351591e-05 PLA2G6, PNKD, CHMP2B, PRRT2, ATP13A2
HP:0001290 Generalized hypotonia HPO 1.00000000 6 (6/933) 6.202366e-03 PLA2G6, ATP1A3, SYNJ1, CSF1R, C19ORF12, TH 1.661605e-02 11 (11/933) 2.146776e-05 PLA2G6, ATP1A3, SYNJ1, SGCE, C19ORF12, TOR1A, NKX6-2, GNAO1, HTRA2, SERAC1, TH
HP:0001344 Absent speech HPO 1.00000000 2 (2/227) 6.389926e-02 WDR45, SLC6A3 2.008011e-02 6 (6/227) 2.594330e-05 GNAO1, WDR45, SERAC1, SLC2A1, SLC6A3, YY1
HP:0007002 Motor axonal neuropathy HPO 1.00000000 1 (1/25) 4.450817e-02 C19ORF12 2.820236e-02 3 (3/25) 3.643716e-05 C19ORF12, COASY, XK
HP:0002131 Episodic ataxia HPO 1.00000000 1 (1/26) 4.624787e-02 ATP1A3 3.182264e-02 3 (3/26) 4.111452e-05 ATP1A3, GNAO1, SLC2A1
HP:0006801 Hyperactive deep tendon reflexes HPO 1.00000000 1 (1/30) 5.317594e-02 C19ORF12 4.932993e-02 3 (3/30) 6.373376e-05 C19ORF12, PRRT2, SLC2A1
HP:0006957 Loss of ability to walk HPO 1.00000000 1 (1/30) 5.317594e-02 MAPT 4.932993e-02 3 (3/30) 6.373376e-05 ADAR, FA2H, VAC14 
prueba <- comparareparkdis$tabledif2