kegg_reason

1,449 entries from KEGG pathway database with variants from ClinVar/dbSNP/OMIM/COSMIC, featuring reasoning traces for mechanistic variant-to-disease prediction across 37 unique diseases.

Usage

from datasets import load_dataset

dataset = load_dataset("weicaijaden/kegg_reason")
example = dataset["train"][0]
print(example)

Downloads last month: 30

question stringclasses 185 values	answer stringclasses 37 values	reasoning stringlengths 1.64k 3.03k	reference_sequence stringlengths 4k 4.07k	variant_sequence stringlengths 4k 4.26k
Chromosome Number: 4 Network Definition of the pathway: (PDE11A,PDE8B) // cAMP -> (PRKAR1A+PRKACA) -> (NR5A1,NR4A1,SP1,PBX1,CREB) => (STAR,CYP11B1) -> Cortisol Genes in the pathway: PDE11A; phosphodiesterase 11A \| PDE8B; phosphodiesterase 8B \| PRKAR1A; protein kinase cAMP-dependent type I regulatory subunit alpha \| P...	cushing syndrome	Step 1: The C>T variant in PDE11A likely results in a missense or nonsense mutation that alters the protein structure or creates a premature stop codon. Step 2: PDE11A encodes phosphodiesterase 11A, an enzyme responsible for hydrolyzing cyclic adenosine monophosphate (cAMP) to its inactive form 5'-AMP. Step 3: Loss of ...	ACTTTATGCTTCCCTACTGCCCTAATTTAGGCCCTGTCATCTCTCACCTGGACAGCCTCCTCACTTAGCTCTCTGTCATCACTCTCTCTACAGTTTCTGCTGCCAGTTTTATTTTTCTAACAGAAAGATCTGATTATACCTCACCTCTTCCCCCACCTACAGCTTTGAAATCATCATGTCTTTCCATTAAACATAAGTTCAAATTCTAGGTCTACTATTATATTCCCTTCAAACTCTAGCCCACCCATCTTCCAAAATTTATTTCCTACCACATCTCTCCCTTCCCAAAATATATCATATTCTTACATCCTTCAGAGCTT...	ACTTTATGCTTCCCTACTGCCCTAATTTAGGCCCTGTCATCTCTCACCTGGACAGCCTCCTCACTTAGCTCTCTGTCATCACTCTCTCTACAGTTTCTGCTGCCAGTTTTATTTTTCTAACAGAAAGATCTGATTATACCTCACCTCTTCCCCCACCTACAGCTTTGAAATCATCATGTCTTTCCATTAAACATAAGTTCAAATTCTAGGTCTACTATTATATTCCCTTCAAACTCTAGCCCACCCATCTTCCAAAATTTATTTCCTACCACATCTCTCCCTTCCCAAAATATATCATATTCTTACATCCTTCAGAGCTT...
Chromosome Number: 4 Network Definition of the pathway: SNCA* // TH -> L-Dopa Genes in the pathway: SNCA; synuclein alpha \| TH; tyrosine hydroxylase Given this context, what is the biological effect of this SNCA allele, specifically what disease does this contribute to?	parkinson's disease	Step 1: The variant KEGG_1163 is an A>G substitution at position 89828155 on chromosome 4, which is located within the SNCA gene encoding alpha-synuclein protein. Step 2: This nucleotide change likely results in a missense mutation, altering an amino acid in the alpha-synuclein protein sequence, potentially affecting i...	TATTGCACATGCTGAAATCACCATGTCCTTACTGCCTAGCAACATTTCCCATAGTTTTCTGTGGAACACTAGTTTCATTCAACCCTAGTAACTAATGAAGAAAGTTTTCAATAATCAAAAAGTTTGAATAACCCTGATTTTAACTATGTAATGCAAATTTCTTTACTGTAGGACATCTCAGATTCCTTAATACGCTAAAGAGAAAATAAAGTATACAAAGTCTCCCAACATTGTACAATGTTAGAAACTTAAGATTGTGAGCCACTGTCCTTCAGAAAACATTTTATAAAATGTCTAATTGTACAAACTTCAGTCTCTCT...	TATTGCACATGCTGAAATCACCATGTCCTTACTGCCTAGCAACATTTCCCATAGTTTTCTGTGGAACACTAGTTTCATTCAACCCTAGTAACTAATGAAGAAAGTTTTCAATAATCAAAAAGTTTGAATAACCCTGATTTTAACTATGTAATGCAAATTTCTTTACTGTAGGACATCTCAGATTCCTTAATACGCTAAAGAGAAAATAAAGTATACAAAGTCTCCCAACATTGTACAATGTTAGAAACTTAAGATTGTGAGCCACTGTCCTTCAGAAAACATTTTATAAAATGTCTAATTGTACAAACTTCAGTCTCTCT...
Chromosome Number: 5 Network Definition of the pathway: PINK1 -> PRKN -> (CISD1,CISD2,FAF2,FKBP8,TOMM70,HK1) // SQSTM1* // LC3 Genes in the pathway: PINK1; PTEN induced kinase 1 \| PRKN; parkin RBR E3 ubiquitin protein ligase \| CISD1; CDGSH iron sulfur domain 1 \| CISD2; CDGSH iron sulfur domain 2 \| FAF2; Fas associated ...	amyotrophic lateral sclerosis	Step 1: The variant KEGG_1426 is a T to TT change (duplication) at position 179836493 on chromosome 5, occurring in the SQSTM1 gene which encodes the p62/sequestosome 1 protein. Step 2: This duplication causes a frameshift mutation, likely resulting in a premature stop codon and truncated p62 protein or nonsense-mediat...	GAGGGAAGGTCAGCAGATAAACAAGTGAACAAAGGTCTCTGGTTTTCCTAGGCAGAGGACCCTGCGGCCTTCCGCAGCGTTTGTGTCCCTGGGTACTTGAGATTAGGGAGTGGTGATGACTCTTAAGGAGCATGCTGCCTTCAAGCATCTGTTTAACAAAGCACATCTTGCACCGCCCTTAATCCATTTAACCCTGAGTGGACACAGCACATGTTTCAGAGAGCACGGGGTTGGGGGTAAGGTCACAGATCAACAGGATAAGAATTTTTCTTAGTACAGAACAAAATGAAAAGTCTCCCATGTCTACTTCTTTCCACACA...	GAGGGAAGGTCAGCAGATAAACAAGTGAACAAAGGTCTCTGGTTTTCCTAGGCAGAGGACCCTGCGGCCTTCCGCAGCGTTTGTGTCCCTGGGTACTTGAGATTAGGGAGTGGTGATGACTCTTAAGGAGCATGCTGCCTTCAAGCATCTGTTTAACAAAGCACATCTTGCACCGCCCTTAATCCATTTAACCCTGAGTGGACACAGCACATGTTTCAGAGAGCACGGGGTTGGGGGTAAGGTCACAGATCAACAGGATAAGAATTTTTCTTAGTACAGAACAAAATGAAAAGTCTCCCATGTCTACTTCTTTCCACACA...
Chromosome Number: 1 Network Definition of the pathway: TARDBP* -\| CxI -> Q Genes in the pathway: TARDBP; TAR DNA binding protein \| ND1; NADH dehydrogenase, subunit 1 (complex I) \| ND2; MTND2 \| ND3; NADH dehydrogenase, subunit 3 (complex I) \| ND4; NADH dehydrogenase, subunit 4 (complex I) \| ND5; NADH dehydrogenase, sub...	amyotrophic lateral sclerosis	Step 1: The variant KEGG_189 is a G>A substitution at position 11022300 on chromosome 1, occurring in the TARDBP gene which encodes the TAR DNA-binding protein (TDP-43). Step 2: This mutation likely results in a missense variant that alters the amino acid sequence of TDP-43, potentially affecting its structure and func...	GGTACGTCTACTTTTTAATGGTTCACTGCTATCCAAGGCGAATGATTTTGTTATATCCCTTACCTTAATGTTTTTTTCATTGTTCATAACATATTTCTGAGTTTTTTTCTTCCTTTTGATTTGATCAGCAAAGCCAAGATGAGCCTTTGAGAAGCAGAAAAGTGTTTGTGGGGCGCTGTACAGAGGACATGACTGAGGATGAGCTGCGGGAGTTCTTCTCTCAGTACGGGGATGTGATGGATGTCTTCATCCCCAAGCCATTCAGGGCCTTTGCCTTTGTTACATTTGCAGATGATCAGGTATTTTTCTCCTTAACGATA...	GGTACGTCTACTTTTTAATGGTTCACTGCTATCCAAGGCGAATGATTTTGTTATATCCCTTACCTTAATGTTTTTTTCATTGTTCATAACATATTTCTGAGTTTTTTTCTTCCTTTTGATTTGATCAGCAAAGCCAAGATGAGCCTTTGAGAAGCAGAAAAGTGTTTGTGGGGCGCTGTACAGAGGACATGACTGAGGATGAGCTGCGGGAGTTCTTCTCTCAGTACGGGGATGTGATGGATGTCTTCATCCCCAAGCCATTCAGGGCCTTTGCCTTTGTTACATTTGCAGATGATCAGGTATTTTTCTCCTTAACGATA...
Chromosome Number: 20 Network Definition of the pathway: GNAS* -> ADCY -> cAMP -> PKA -> CREB -> ACTH Genes in the pathway: GNAS; GNAS complex locus \| ADCY1; adenylate cyclase 1 \| ADCY2; adenylate cyclase 2 \| ADCY3; adenylate cyclase 3 \| ADCY4; adenylate cyclase 4 \| ADCY5; adenylate cyclase 5 \| ADCY6; adenylate cyclase...	cushing syndrome	Step 1: The variant KEGG_272 is an A>C substitution at position 58909540 on chromosome 20, which is located in the GNAS gene that encodes the alpha subunit of the stimulatory G protein (Gsα). Step 2: GNAS mutations can affect the GTPase activity of the Gsα protein, potentially leading to a constitutively active protein...	AGGGAGACCCAGTTTCGTTAATTAACAGTAGCTTAGCCAGATTGTTGAATTTTGTCGGGTTTCGTTTTCTCTCTCAAATCATTTAGAAGTTTTTGGGGTTTTTTTAAGCAACACTTAATTACTCCTGAAACTTTGTCTGAAAACGCACCATTTGTATAGATCATGAAAAGTTTTAAGGAAACTCAGAGAAAAAGAGAACAACGCAGCTTAAAACTTTTAAAATGTCCTCCCTCACCCGTGGCTCAAACAGCCCTGCATCTGCCGTGGCCGGCACGTTTCTGGTTGAACTGCCTTTATGTTAAAGTTCAGATACTGGTAGT...	AGGGAGACCCAGTTTCGTTAATTAACAGTAGCTTAGCCAGATTGTTGAATTTTGTCGGGTTTCGTTTTCTCTCTCAAATCATTTAGAAGTTTTTGGGGTTTTTTTAAGCAACACTTAATTACTCCTGAAACTTTGTCTGAAAACGCACCATTTGTATAGATCATGAAAAGTTTTAAGGAAACTCAGAGAAAAAGAGAACAACGCAGCTTAAAACTTTTAAAATGTCCTCCCTCACCCGTGGCTCAAACAGCCCTGCATCTGCCGTGGCCGGCACGTTTCTGGTTGAACTGCCTTTATGTTAAAGTTCAGATACTGGTAGT...
Chromosome Number: 1 Network Definition of the pathway: PINK1* // (HTRA2,TRAP1) // CYCS == APAF1 -> CASP9 -> CASP3 Genes in the pathway: PINK1; PTEN induced kinase 1 \| HTRA2; HtrA serine peptidase 2 \| TRAP1; TNF receptor associated protein 1 \| CYCS; cytochrome c, somatic \| APAF1; apoptotic peptidase activating factor 1...	parkinson's disease	Step 1: The variant is a duplication (AGTTAG>AGTTAGTTAG) in the PINK1 gene, which encodes PTEN-induced kinase 1, a mitochondrial serine/threonine-protein kinase. Step 2: This duplication likely results in the insertion of two amino acids (serine and leucine) in the protein sequence, potentially disrupting the protein's...	CCCTGGCTGGTGATCGCAGATTTTGGCTGCTGCCTGGCTGATGAGAGCATCGGCCTGCAGTTGCCCTTCAGCAGCTGGTACGTGGATCGGGGCGGAAACGGCTGTCTGATGGCCCCAGAGGTGAGTCCCGAGTGTGTCATGCGCCATCGGCAGCCCTTCCCCCACATGTCCACTGAATGCAGGAGACTCGATGCCTTGTGATAACCCAACACCTCCATCTTTTCTGACCCATAATTTGGCACAAGTTCCTTCCCTGCCACTTTGCTTTCCTCCGGCGTTCCCTCATGTTCCAGGAGAATGCAAGTCCTGTCACATAAACC...	CCCTGGCTGGTGATCGCAGATTTTGGCTGCTGCCTGGCTGATGAGAGCATCGGCCTGCAGTTGCCCTTCAGCAGCTGGTACGTGGATCGGGGCGGAAACGGCTGTCTGATGGCCCCAGAGGTGAGTCCCGAGTGTGTCATGCGCCATCGGCAGCCCTTCCCCCACATGTCCACTGAATGCAGGAGACTCGATGCCTTGTGATAACCCAACACCTCCATCTTTTCTGACCCATAATTTGGCACAAGTTCCTTCCCTGCCACTTTGCTTTCCTCCGGCGTTCCCTCATGTTCCAGGAGAATGCAAGTCCTGTCACATAAACC...
Chromosome Number: 19 Network Definition of the pathway: Ca2+(extracellular) -- CACNA1A* -> Ca2+ Genes in the pathway: CACNA1A; calcium voltage-gated channel subunit alpha1 A Given this context, what is the biological effect of this CACNA1A allele, specifically what disease does this contribute to?	spinocerebellar ataxia	Step 1: The variant is an A>T substitution at position 13257473 on chromosome 19, occurring in the CACNA1A gene. Step 2: CACNA1A encodes the alpha-1A subunit of the P/Q-type voltage-gated calcium channel, which is highly expressed in cerebellar neurons. Step 3: This channel regulates calcium influx into neurons, contro...	AAAACTTGCACTGACATTTCCCCATTATTGCATGGCTAATACAAACATGGGAAGTGGGTACTATCAATGGCCTCACTTTGCAGATCACCAAAATAGAGGCTTAGAAAGGTTAAACCACTTGCCTGAGGTGACACAGCTACCGAGTGTGCCAAATCAAATTGAAGCCTAATCCTTCTTCCCCTTCCTCCCTCCCTCGCTCCCTCCCTCCTTCCTTCCTTCCTCCCTCCTTCCTTCCCTCCCTCCCTCCTTCTCTCCCTCCCTCCTTCCCTCCCTCCCTCCTTCCCTCCCTCCTTCCCTCCCTCCTTTCCTTCCTTCCTCCC...	AAAACTTGCACTGACATTTCCCCATTATTGCATGGCTAATACAAACATGGGAAGTGGGTACTATCAATGGCCTCACTTTGCAGATCACCAAAATAGAGGCTTAGAAAGGTTAAACCACTTGCCTGAGGTGACACAGCTACCGAGTGTGCCAAATCAAATTGAAGCCTAATCCTTCTTCCCCTTCCTCCCTCCCTCGCTCCCTCCCTCCTTCCTTCCTTCCTCCCTCCTTCCTTCCCTCCCTCCCTCCTTCTCTCCCTCCCTCCTTCCCTCCCTCCCTCCTTCCCTCCCTCCTTCCCTCCCTCCTTTCCTTCCTTCCTCCC...
Chromosome Number: 20 Network Definition of the pathway: PRNP* -\| VGCC(N,L-type) -> Ca2+ Genes in the pathway: PRNP; prion protein \| CACNA1B; calcium voltage-gated channel subunit alpha1 B \| CACNA1C; calcium voltage-gated channel subunit alpha1 C \| CACNA1D; calcium voltage-gated channel subunit alpha1 D \| CACNA1F; calc...	creutzfeldt-jakob disease	Step 1: The T>C mutation at position 4699812 on chromosome 20 occurs in the PRNP gene, which encodes the prion protein (PrP). Step 2: This mutation likely alters the amino acid sequence of the prion protein, affecting its three-dimensional structure and stability. Step 3: The structural change promotes misfolding of th...	TGATGGAAGCACCGAATAAGATGGTCATGTTGGAAAAATTGAGAAGCTGAGGTGCTTAGCATTGATTTTCAAGGTAGAGCTACTGAGATTTGCTGATAGATCCAATGTATGCTGGGAGAGAAAATTCAGTCACTCTAGAGCATTGGCTGGATTTGTCACCCATTGCAGCGAATGGAGAAGGTGCTGACATAAAAGCCCTTTAGACTGAAAGCTACTGACTGAGGGGATGGTGCCCTAGTTTGATTTCCTGGGGTGTATGAGTAGCAGGGAGGCCAAGAGCTGGGCCTCACGAGATTGTGGGGACTACATCAGGGAAGCAG...	TGATGGAAGCACCGAATAAGATGGTCATGTTGGAAAAATTGAGAAGCTGAGGTGCTTAGCATTGATTTTCAAGGTAGAGCTACTGAGATTTGCTGATAGATCCAATGTATGCTGGGAGAGAAAATTCAGTCACTCTAGAGCATTGGCTGGATTTGTCACCCATTGCAGCGAATGGAGAAGGTGCTGACATAAAAGCCCTTTAGACTGAAAGCTACTGACTGAGGGGATGGTGCCCTAGTTTGATTTCCTGGGGTGTATGAGTAGCAGGGAGGCCAAGAGCTGGGCCTCACGAGATTGTGGGGACTACATCAGGGAAGCAG...
Chromosome Number: 6 Network Definition of the pathway: PRKN* // BAX -> CYCS == APAF1 -> CASP9 -> CASP3 Genes in the pathway: PRKN; parkin RBR E3 ubiquitin protein ligase \| BAX; BCL2 associated X, apoptosis regulator \| CYCS; cytochrome c, somatic \| APAF1; apoptotic peptidase activating factor 1 \| CASP9; caspase 9 \| CAS...	parkinson's disease	Step 1: The G>T substitution at position 161785819 on chromosome 6 occurs in the PRKN gene, which encodes Parkin, an E3 ubiquitin ligase. Step 2: This mutation likely alters a critical amino acid in the Parkin protein, disrupting its three-dimensional structure and compromising its E3 ubiquitin ligase activity. Step 3:...	TAACATATATTATGTGAATCTTAGTTTTAAAAATCATTGCATTATTGGTAGATATGCTTAAAAGTGAGTATCATAATTTACAAAGTCAACAAAGAAATTAATTTATTCCATTTGGATCTTTTTATCATTTGGAGGTATATTTTTCAGCTATAATTGACATTAAAACTAAATCTTGAAATAAATTGAACTTAAAACCTCACCATTGAGTCAAGGTATCCCATAGTTTCAAATTAAGTTTTGAAGAATTAATGAAACATATTTAGTCACATTGCAGTCATTTATACATAGAGAGAGATAGGAACTTTTACTTCACTCCAGGT...	TAACATATATTATGTGAATCTTAGTTTTAAAAATCATTGCATTATTGGTAGATATGCTTAAAAGTGAGTATCATAATTTACAAAGTCAACAAAGAAATTAATTTATTCCATTTGGATCTTTTTATCATTTGGAGGTATATTTTTCAGCTATAATTGACATTAAAACTAAATCTTGAAATAAATTGAACTTAAAACCTCACCATTGAGTCAAGGTATCCCATAGTTTCAAATTAAGTTTTGAAGAATTAATGAAACATATTTAGTCACATTGCAGTCATTTATACATAGAGAGAGATAGGAACTTTTACTTCACTCCAGGT...
Chromosome Number: 14 Network Definition of the pathway: PSEN1* -\| ERN1 -> XBP1 Genes in the pathway: PSEN1; presenilin 1 \| ERN1; endoplasmic reticulum to nucleus signaling 1 \| XBP1; X-box binding protein 1 Given this context, what is the biological effect of this PSEN1 allele, specifically what disease does this cont...	alzheimer's disease	Step 1: The variant KEGG_995 represents a G>C substitution at position 73198093 on chromosome 14, occurring within the PSEN1 gene that encodes presenilin 1 protein. Step 2: Presenilin 1 is a catalytic subunit of the gamma-secretase complex, which cleaves amyloid precursor protein (APP) and is critical for proper APP pr...	ATTCTCGGCTCCATTTTTACAAGATTTCAAGATTTAATTTGTCAAAAAAGTTCTGAAATTTTCAAAGCAAAAGCAATTTTAATTTAATTGCTCTAAAAAATAAGCAGATTTATCATTTAGCAATTCTTTAAGGGAGAGTGTATCATAAAACTGAAATAGTACTGAATGTGGCAGAATCAAACAAGTTGAAAATCTCATCACTTCAGAGCAGGGCAGACTTCTCATTCAAACAAATTGAGGTAGAAGTGGTGAGAGTAGAGATTTCTTTGTGTATGTGTGTTTTATTACTGTACTATATTATATTATAGTTCTATATATAC...	ATTCTCGGCTCCATTTTTACAAGATTTCAAGATTTAATTTGTCAAAAAAGTTCTGAAATTTTCAAAGCAAAAGCAATTTTAATTTAATTGCTCTAAAAAATAAGCAGATTTATCATTTAGCAATTCTTTAAGGGAGAGTGTATCATAAAACTGAAATAGTACTGAATGTGGCAGAATCAAACAAGTTGAAAATCTCATCACTTCAGAGCAGGGCAGACTTCTCATTCAAACAAATTGAGGTAGAAGTGGTGAGAGTAGAGATTTCTTTGTGTATGTGTGTTTTATTACTGTACTATATTATATTATAGTTCTATATATAC...
Chromosome Number: 4 Network Definition of the pathway: SNCA* -\| CxI -> Q Genes in the pathway: SNCA; synuclein alpha \| ND1; NADH dehydrogenase, subunit 1 (complex I) \| ND2; MTND2 \| ND3; NADH dehydrogenase, subunit 3 (complex I) \| ND4; NADH dehydrogenase, subunit 4 (complex I) \| ND5; NADH dehydrogenase, subunit 5 (comp...	parkinson's disease	Step 1: The variant KEGG_1166 is an A>C substitution at position 89828155 on chromosome 4, occurring in the SNCA gene which encodes alpha-synuclein protein. Step 2: This mutation likely results in a missense variant that changes an amino acid in the alpha-synuclein protein, potentially affecting its structure and funct...	TATTGCACATGCTGAAATCACCATGTCCTTACTGCCTAGCAACATTTCCCATAGTTTTCTGTGGAACACTAGTTTCATTCAACCCTAGTAACTAATGAAGAAAGTTTTCAATAATCAAAAAGTTTGAATAACCCTGATTTTAACTATGTAATGCAAATTTCTTTACTGTAGGACATCTCAGATTCCTTAATACGCTAAAGAGAAAATAAAGTATACAAAGTCTCCCAACATTGTACAATGTTAGAAACTTAAGATTGTGAGCCACTGTCCTTCAGAAAACATTTTATAAAATGTCTAATTGTACAAACTTCAGTCTCTCT...	TATTGCACATGCTGAAATCACCATGTCCTTACTGCCTAGCAACATTTCCCATAGTTTTCTGTGGAACACTAGTTTCATTCAACCCTAGTAACTAATGAAGAAAGTTTTCAATAATCAAAAAGTTTGAATAACCCTGATTTTAACTATGTAATGCAAATTTCTTTACTGTAGGACATCTCAGATTCCTTAATACGCTAAAGAGAAAATAAAGTATACAAAGTCTCCCAACATTGTACAATGTTAGAAACTTAAGATTGTGAGCCACTGTCCTTCAGAAAACATTTTATAAAATGTCTAATTGTACAAACTTCAGTCTCTCT...
Chromosome Number: 21 Network Definition of the pathway: APP* -> Abeta -\| 26S Genes in the pathway: APP; amyloid beta precursor protein \| PSMA6; proteasome 20S subunit alpha 6 \| PSMA2; proteasome 20S subunit alpha 2 \| PSMA4; proteasome 20S subunit alpha 4 \| PSMA7; proteasome 20S subunit alpha 7 \| PSMA8; proteasome 20S ...	alzheimer's disease	Step 1: The C>G mutation at position 25891783 on chromosome 21 occurs in the APP gene, which encodes the amyloid precursor protein. Step 2: This mutation likely alters the proteolytic processing of APP, potentially affecting the cleavage sites for β-secretase (BACE1) and γ-secretase. Step 3: Altered APP processing lead...	TTGCAGTGAGCGGAGATCATGCCACTGCACTCCAGCCTGGGTGAAAGAGCAAGACTCCATCTCAAAAAACAAAGAAACAACAACAACAAAAGAAAACAACAAAACCATGAAAAAAACCAAAACAACAACAGCAGCAAAAAAGGGGTCTTGAATTACTCAAGTATGAAGACATCTTTATTTGCTCAAATATGGAATTAAATTTTTTTAAAAATTAATTTGAGCAGAAATGAAATAAGCTGATACTAATGAAAACCTATCTTACACTGTTTTGAGGGACATAAGCTTAGATACTATCACAAAAGGTGCAATGGCCAAACATG...	TTGCAGTGAGCGGAGATCATGCCACTGCACTCCAGCCTGGGTGAAAGAGCAAGACTCCATCTCAAAAAACAAAGAAACAACAACAACAAAAGAAAACAACAAAACCATGAAAAAAACCAAAACAACAACAGCAGCAAAAAAGGGGTCTTGAATTACTCAAGTATGAAGACATCTTTATTTGCTCAAATATGGAATTAAATTTTTTTAAAAATTAATTTGAGCAGAAATGAAATAAGCTGATACTAATGAAAACCTATCTTACACTGTTTTGAGGGACATAAGCTTAGATACTATCACAAAAGGTGCAATGGCCAAACATG...
Chromosome Number: 1 Network Definition of the pathway: DJ1* // (DAXX+ASK1) -> JNK Genes in the pathway: PARK7; Parkinsonism associated deglycase \| DAXX; death domain associated protein \| MAP3K5; mitogen-activated protein kinase kinase kinase 5 \| MAPK8; mitogen-activated protein kinase 8 \| MAPK9; mitogen-activated prot...	parkinson's disease	Step 1: The T>C variant at position 7984980 on chromosome 1 occurs in the PARK7 gene, which encodes the DJ-1 protein (Parkinsonism associated deglycase). Step 2: DJ-1 normally functions as a multifunctional protein with roles in oxidative stress response, acting as a peroxiredoxin-like peroxidase that scavenges hydroge...	GCAGTGGCTTGGTTTCTAATGACAGTAAGACAAGTTCCTATAGCCATTGTTAATCTCCTTGGAAAAGAAATGAACACTGTGTGGTTTCAGAAGCTCATTAATATAGCAGAAGCACTCTGCTTCTGTTTGAAGGGAGGTTTTCAGATGAATTTTTCTGCGTGTTCATTGAACAGACGTTTCCTAAGCTCCTCCTTAGTGCCTGGCACTGGGAACAGAAGAAGGAAGAAGAGAAAGCTGTGCCCTCAGGGTGTTCTCAGGTCCGCACTGAGCGGTGGTGACCAGAGCCACCCGCCTGCCTGCGTGGCCGGTGCATCAGGATA...	GCAGTGGCTTGGTTTCTAATGACAGTAAGACAAGTTCCTATAGCCATTGTTAATCTCCTTGGAAAAGAAATGAACACTGTGTGGTTTCAGAAGCTCATTAATATAGCAGAAGCACTCTGCTTCTGTTTGAAGGGAGGTTTTCAGATGAATTTTTCTGCGTGTTCATTGAACAGACGTTTCCTAAGCTCCTCCTTAGTGCCTGGCACTGGGAACAGAAGAAGGAAGAAGAGAAAGCTGTGCCCTCAGGGTGTTCTCAGGTCCGCACTGAGCGGTGGTGACCAGAGCCACCCGCCTGCCTGCGTGGCCGGTGCATCAGGATA...
Chromosome Number: 1 Network Definition of the pathway: DJ1* // BCL2L1 // BAX Genes in the pathway: PARK7; Parkinsonism associated deglycase \| BCL2L1; BCL2 like 1 \| BAX; BCL2 associated X, apoptosis regulator Given this context, what is the biological effect of this PARK7 allele, specifically what disease does this co...	parkinson's disease	Step 1: The G>A substitution at position 7962862 on chromosome 1 occurs in the PARK7 gene (also known as DJ-1), likely resulting in a cysteine to tyrosine amino acid change at position 106 (C106Y) in the DJ-1 protein. Step 2: Cysteine 106 is a highly conserved residue in the DJ-1 protein and functions as a critical oxi...	TAGCGTTGGCAGAGTTCTGTAGGGTGACTATAGTTAACAGTAATCTGTTGTATATTTTAAAATGTTATTATTGAAGAGAGTAACTGGAATGTTCCCAGTATAAAGACAAATGTTTAAGGTGATAGAGATCTCATTTACCCTGATTTAATCATTACACATTATATGAAAGTATCAAAATACCACATGTACCCAGAAAACACATACGTCTCTTACATATCAATAAATACAACTTGAGATTATGATGTAAATACATCTGACCAACTTGGTACTTATTAGACTTATGTGCGCAGCACTGCTCTAGTCCTGTGGGTGCAGCAGCA...	TAGCGTTGGCAGAGTTCTGTAGGGTGACTATAGTTAACAGTAATCTGTTGTATATTTTAAAATGTTATTATTGAAGAGAGTAACTGGAATGTTCCCAGTATAAAGACAAATGTTTAAGGTGATAGAGATCTCATTTACCCTGATTTAATCATTACACATTATATGAAAGTATCAAAATACCACATGTACCCAGAAAACACATACGTCTCTTACATATCAATAAATACAACTTGAGATTATGATGTAAATACATCTGACCAACTTGGTACTTATTAGACTTATGTGCGCAGCACTGCTCTAGTCCTGTGGGTGCAGCAGCA...
Chromosome Number: 12 Network Definition of the pathway: KRAS* -> RALGDS -> RAL Genes in the pathway: KRAS; KRAS proto-oncogene, GTPase \| RALGDS; ral guanine nucleotide dissociation stimulator \| RALA; RAS like proto-oncogene A \| RALB; RAS like proto-oncogene B Given this context, what is the biological effect of this ...	colorectal cancer	Step 1: The variant KEGG_529 is a C>G substitution at position 25245349 on chromosome 12, which is located in the KRAS gene. Step 2: This mutation likely occurs in codon 12 of KRAS, resulting in a glycine to valine amino acid substitution (G12V), a common oncogenic mutation. Step 3: The G12V mutation impairs the intrin...	GTCAGTTTCAAAGTTCACAGGTAACCAATGCTTCCCAGAGTCAAGTCTTCTGGTTTGGCAGAAATCATAAGCAGAGTTATAGGTTTAAGTTTATAAACTTTTTCAGCCTTCCGCCCAAATAAAGGCTTAACTGTTAGCTTTATTTCTTCAACATTTATATTGCATTTTAACAATCATTAGCAAAAGGTTTCCTAACCCACTTTATCACATTCATGACGTCATGCTGTATATACTCATATAGCACTCATGACCTCTGATTGGAAACAAAGTGTAATGGAATTTCTCAGATTTTCAGGGAAGACAGACAGCATTTCCAGTAA...	GTCAGTTTCAAAGTTCACAGGTAACCAATGCTTCCCAGAGTCAAGTCTTCTGGTTTGGCAGAAATCATAAGCAGAGTTATAGGTTTAAGTTTATAAACTTTTTCAGCCTTCCGCCCAAATAAAGGCTTAACTGTTAGCTTTATTTCTTCAACATTTATATTGCATTTTAACAATCATTAGCAAAAGGTTTCCTAACCCACTTTATCACATTCATGACGTCATGCTGTATATACTCATATAGCACTCATGACCTCTGATTGGAAACAAAGTGTAATGGAATTTCTCAGATTTTCAGGGAAGACAGACAGCATTTCCAGTAA...
Chromosome Number: 2 Network Definition of the pathway: TG+(Iodide+Tyr) -- TPO* // TG+(MIT,DIT) -- TPO* // TG+(T3,T4) Genes in the pathway: TG; thyroglobulin \| TPO; thyroid peroxidase Given this context, what is the biological effect of this TPO allele, specifically what disease does this contribute to?	thyroid dyshormonogenesis	Step 1: The variant KEGG_1326 is a duplication of a cytosine (C) nucleotide in the TPO gene, resulting in an insertion of an additional C in a string of seven C nucleotides. Step 2: This insertion causes a frameshift mutation, altering the reading frame of the TPO gene downstream of position 1503975. Step 3: The frames...	GGGCAGAAGCTGCTCCAAGGGAACTCCCCGAGAGGGATGCAGGGATGTGTTGGCAGCTGCCATTCCCATTCTGAGGACCCCATTGCACATCCCAGGGGATGGAGAGAAAATGGGCTTGTAGCGTTCATGGGTGATGACTTTGATTTTTCACACGATCATGATGGAAACACTCCCTACCCCAGAGGCGGCTGCAGATGCCTTCACACAGCTCTGGTGCTCCACAGCTCTGCATAACGGGATGCAGGAGGGGCTGGTTCCAGGGGCAGCTTTAGCCAAGAAAGACCTTCTAGGTTTAACAGCCTTGACATGGTTACCTGTAC...	GGGCAGAAGCTGCTCCAAGGGAACTCCCCGAGAGGGATGCAGGGATGTGTTGGCAGCTGCCATTCCCATTCTGAGGACCCCATTGCACATCCCAGGGGATGGAGAGAAAATGGGCTTGTAGCGTTCATGGGTGATGACTTTGATTTTTCACACGATCATGATGGAAACACTCCCTACCCCAGAGGCGGCTGCAGATGCCTTCACACAGCTCTGGTGCTCCACAGCTCTGCATAACGGGATGCAGGAGGGGCTGGTTCCAGGGGCAGCTTTAGCCAAGAAAGACCTTCTAGGTTTAACAGCCTTGACATGGTTACCTGTAC...
Chromosome Number: 9 Network Definition of the pathway: CDKN2A* // (CCND+CDK4/6) -> RB1 // E2F Genes in the pathway: CDKN2A; cyclin dependent kinase inhibitor 2A \| CCND1; cyclin D1 \| CCND2; cyclin D2 \| CCND3; cyclin D3 \| CDK4; cyclin dependent kinase 4 \| CDK6; cyclin dependent kinase 6 \| RB1; RB transcriptional corepre...	pancreatic ductal adenocarcinoma	Step 1: The variant is an A>T substitution at position 21970989 on chromosome 9, occurring in the CDKN2A gene. Step 2: CDKN2A encodes multiple tumor suppressor proteins through alternative reading frames, most notably p16INK4a and p14ARF. Step 3: The p16INK4a protein functions as a cyclin-dependent kinase inhibitor tha...	CCGTAGCTTGCATTAGATTCTCCGACCACTCTTTAGCTTCTCCTCCTATTCACACTTCATATTTACCCATTGCATTGGTTTTATAAACTCGCTCTCTGAAAATAGATTGTTATCTTCCTTAACGTCTGTTTCCCAGGTCGGGCAAGATAGCTTGGGACTGTAATCCCAGTACTTTAGGAGGAGGAGGGGGGATGATCGCTTGAGCCCAGATAACATGGTGAGACCTTCGTCTCTATTAAACAAACAAACAAACCCAGGCGTCGTGGCGTGCACCTGTGGTCCCAGCTAGTCGGGAGGCTCAGGTGGGAGAACCCCTTGAG...	CCGTAGCTTGCATTAGATTCTCCGACCACTCTTTAGCTTCTCCTCCTATTCACACTTCATATTTACCCATTGCATTGGTTTTATAAACTCGCTCTCTGAAAATAGATTGTTATCTTCCTTAACGTCTGTTTCCCAGGTCGGGCAAGATAGCTTGGGACTGTAATCCCAGTACTTTAGGAGGAGGAGGGGGGATGATCGCTTGAGCCCAGATAACATGGTGAGACCTTCGTCTCTATTAAACAAACAAACAAACCCAGGCGTCGTGGCGTGCACCTGTGGTCCCAGCTAGTCGGGAGGCTCAGGTGGGAGAACCCCTTGAG...