diff --git a/data/STRchive-loci.multi-disease.json b/data/STRchive-loci.multi-disease.json new file mode 100644 index 00000000..d70ea7ed --- /dev/null +++ b/data/STRchive-loci.multi-disease.json @@ -0,0 +1,261 @@ +[ +{ + "id": "FXS_FMR1", + "gene": "FMR1", + "chrom": "chrX", + "start_hg38": 147912049, + "stop_hg38": 147912111, + "start_hg19": 146993567, + "stop_hg19": 146993629, + "start_t2t": 146176677, + "stop_t2t": 146176769, + "diseases": [ + { + "disease_id": "FXS", + "disease": "Fragile X syndrome (FXS)", + "evidence": ["Definitive"], + "inheritance": ["XD"], + "association_type": ["Mendelian"], + "disease_description": "A genetic syndrome caused by mutations in the FMR1 gene which is responsible for the expression of the fragile X messenger ribonucleoprotein 1 (FMR1) protein. This protein participates in neural development. This syndrome is manifested with mental, emotional, behavioral, physical, and learning disabilities [@mondo:0010383].", + "prevalence": "14/100000", + "prevalence_details": "Incidence of full mutation and therefore disease prevlence in males is estimated to be between 14/100,000 - 19/100,000 [@genereviews:NBK1384]. Female prevalence is expected to be half the male prevelence and ahs been estimated at 9/100,000 [@pmid:24700618]. Known carrier frequency is approximately 300-500/100,000 but detected was 11/100,000 [@pmid:29100084]. FX premutation carrier prevelence is 1:290-855 males, 1:148-300 females [@isbn:978-3-031-66932-3]. Found worldwide [@genereviews:NBK1384]. In Thailand, 1 in 600 women carry a premutation, and 1 in 400 carry a 'gray zone' allele [@pmid:39320553].", + "age_onset": "Typical: FXS 1 to 'first several years of life'. Average age of diagnosis is 36 months for boys and 41.6 months for girls with families reporting an average of 18 months lapsed between first concerns and a diagnosis [@pmid:19581269]. Delays are typically not detected during the first year of life, often becoming apparent by 24 months [@pmid:40004478].", + "age_onset_min": 0.0, + "age_onset_max": 2.0, + "typ_age_onset_min": 1.0, + "typ_age_onset_max": 2.0, + "mechanism": "LoF", + "mechanism_detail": "Loss of function via transcriptional silencing in FXS [@pmid:16205714; @pmid:36169768]. PRKGG appears to modulate neurotoxicity [@pmid:41507195].", + "benign_min": 5, + "benign_max": 44, + "intermediate_min": 45, + "intermediate_max": 200, + "pathogenic_min": 201, + "pathogenic_max": 2000, + "hpo_terms": null, + "gard": ["6464"], + "genereviews": ["NBK1384"], + "malacard": ["FRG001"], + "medgen": ["8912"], + "mondo": ["0010383"], + "omim": ["300624"], + "orphanet": ["908"] + }, + { + "disease_id": "FXTAS", + "disease": "Fragile X-associated tremor/ataxia syndrome (FXTAS)", + "evidence": ["Definitive"], + "inheritance": ["XD"], + "association_type": ["Mendelian"], + "disease_description": "Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia [@mondo:0010382]. FXTAS occurs in a subset of individuals who have an FMR1 premutation. It is more common among males who are hemizygous for the premutation (40%) than among females who are heterozygous for the premutation (16%-20%) [@genereviews:NBK1384].", + "prevalence": null, + "prevalence_details": "FX premutation carriers 1:290-855 males, 1:148-300 females [@isbn:978-3-031-66932-3]. Found worldwide [@genereviews:NBK1384]. In Thailand, 1 in 600 women carry a premutation, and 1 in 400 carry a 'gray zone' allele [@pmid:39320553].", + "age_onset": "60-65 [@genereviews:NBK1384]; Range: 0 [@url:https://www.uptodate.com/contents/fragile-x-syndrome-clinical-features-and-diagnosis-in-children-and-adolescents] - 78 [@pmid:17427188]; detailed description of typical symptom onset and diagnosis available from Arnold et al [@isbn:978-3-031-66932-3].", + "age_onset_min": 0.0, + "age_onset_max": 78.0, + "typ_age_onset_min": 60.0, + "typ_age_onset_max": 65.0, + "mechanism": "GoF", + "mechanism_detail": "RNA gain of function in FXTAS/FXPOI [@pmid:16205714; @pmid:36169768]. PRKGG appears to modulate neurotoxicity [@pmid:41507195].", + "benign_min": 5, + "benign_max": 44, + "intermediate_min": 45, + "intermediate_max": 54, + "pathogenic_min": 55, + "pathogenic_max": 200, + "hpo_terms": null, + "gard": ["16806"], + "genereviews": ["NBK1384"], + "malacard": ["FRG008"], + "medgen": ["333403"], + "mondo": ["0010382"], + "omim": ["300623"], + "orphanet": ["93256"] + }, + { + "disease_id": "POF1", + "disease": "Fragile X-associated primary ovarian insufficiency FXPOI/Premature ovarian failure POF1", + "evidence": ["Definitive"], + "inheritance": ["XD"], + "association_type": ["Mendelian"], + "disease_description": "Primary ovarian failure caused bya mutation in the FMR1 gene [@mondo:0010706]. Can cause irregular menstrual cycles, early menopause, infertility, and elevated follicle stimulating hormone (FSH) [@medgen:1644269].", + "prevalence": "1/755", + "prevalence_details": "Observed in 20% of women who carry the FMR1 premutation allele compared to ovarian failure seen in 1% in the general population [@genereviews:NBK1384]. Risk is dependent on the number of CGG repeats [@pmid:18574214]. Premutation carrier prevalence is 1:148-300 in females [@isbn:978-3-031-66932-3]. Overall prevelence of 1/755 in women is estimated by multiplying the premutation carrier rate of 1/151 [@pmid:22619118] by 20% ovarian failure rate [@genereviews:NBK1384].", + "age_onset": "Defined as ovarian failure before age 40 [@genereviews:NBK1384]. Individuals homozygous for the premutation had earlier cessation of menses at age 20.4±4.8 [@pmid:25050920].", + "age_onset_min": 15.0, + "age_onset_max": 40.0, + "typ_age_onset_min": 20.0, + "typ_age_onset_max": 40.0, + "mechanism": "GoF", + "mechanism_detail": "RNA gain of function in FXTAS/FXPOI [@pmid:16205714; @pmid:36169768].", + "benign_min": 5, + "benign_max": 44, + "intermediate_min": 45, + "intermediate_max": 54, + "pathogenic_min": 55, + "pathogenic_max": 200, + "hpo_terms": null, + "gard": ["2811"], + "genereviews": ["NBK1384"], + "malacard": ["PRM405"], + "medgen": ["1644269"], + "mondo": ["0010706"], + "omim": ["311360"], + "orphanet": ["642691"] + } + ], + "details": "Intermediate or 'gray zone' occur at 45-54 alleles and may be unstable enough to expand into the premutation range, as well as associate with parkinsonism [@pmid:32463542; @genereviews:NBK1384]. FXTAS/POI occurs at 55-200 repeats, FXS >200, late onset; AGG and CTG interruptions documented [@genereviews:NBK1384; @pmid:29868108]. Women with the premutation have been reported showing episodic memory deficits, similar to those seen in AD [@pmid:41555826].", + "year": "1992 [@pmid:1605194]; causative gene discovered in 1991 [@pmid:1710175]", + "location_in_gene": "5' UTR", + "gene_strand": "+", + "reference_motif_reference_orientation": ["CGG"], + "pathogenic_motif_reference_orientation": ["CGG"], + "benign_motif_reference_orientation": [], + "unknown_motif_reference_orientation": [], + "pathogenic_motif_gene_orientation": ["CGG"], + "benign_motif_gene_orientation": [], + "unknown_motif_gene_orientation": [], + "locus_structure": [], + "motif_len": 3, + "ref_copies": 20.6667, + "novel": "ref", + "gnomad": ["FMR1"], + "stripy": ["FMR1"], + "tr_atlas": ["TR173944"], + "webstr_hg38": ["885222"], + "webstr_hg19": ["Expansion_FXS/FMR1"], + "disease_tags": ["phenotypic_spectrum", "ataxia"], + "locus_tags": ["supported_evidence", "somatic_instability", "anticipation", "maternal_expansion", "length_affects_onset", "length_affects_penetrance", "length_affects_phenotype", "length_affects_severity", "motif_affects_instability"], + "references": ["genereviews:NBK1384", "url:https://www.uptodate.com/contents/fragile-x-syndrome-clinical-features-and-diagnosis-in-children-and-adolescents", "pmid:17427188", "isbn:978-3-031-66932-3", "pmid:16205714", "pmid:36169768", "pmid:32463542", "pmid:29868108", "pmid:24700618", "pmid:29100084", "pmid:39320553", "pmid:1605194", "pmid:1710175", "mondo:0010383", "mondo:0010706", "mondo:0010382"], + "additional_literature": ["pmid:41557506", "pmid:41555826", "pmid:41523206", "pmid:41514368", "pmid:41507195", "pmid:41409170", "pmid:41386846", "pmid:41385812", "pmid:41372183", "pmid:41351347", "pmid:41278766", "pmid:41256123", "pmid:41167304", "pmid:41145158", "pmid:41120736", "pmid:41098569", "pmid:41074692", "pmid:41028987", "pmid:41015363", "pmid:40980401", "pmid:40940631", "pmid:40877251", "pmid:40869951", "pmid:40879637", "pmid:40778130", "pmid:40653294", 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"pmid:8698331", "pmid:8826482", "pmid:8826479", "pmid:8725793", "pmid:8636996", "pmid:8673086", "pmid:8664297", "pmid:8644711", "pmid:8626781", "pmid:8872026", "pmid:8800930", "pmid:8519769", "pmid:8634688", "pmid:7499428", "pmid:8589687", "pmid:7581460", "pmid:8593539", "pmid:8579216", "pmid:8559749", "pmid:7541938", "pmid:7761473", "pmid:7758107", "pmid:7732383", "pmid:7783163", "pmid:8750357", "pmid:7825564", "pmid:7717734", "pmid:7881407", "pmid:7864047", "pmid:7927336", "pmid:7849707", "pmid:7987398", "pmid:8023854", "pmid:8197163", "pmid:8162055", "pmid:8275089", "pmid:8244331", "pmid:8237919", "pmid:7902319", "pmid:7692601", "pmid:8242066", "pmid:8334699", "pmid:1642231", "pmid:1605199"] +}, + +{ + "id": "NIID_NOTCH2NLC", + "disease_id": "NIID", + "gene": "NOTCH2NLC", + "evidence": ["Definitive"], + "chrom": "chr1", + "start_hg38": 149390802, + "stop_hg38": 149390842, + "start_hg19": 145209323, + "stop_hg19": 145209354, + "start_t2t": 148519695, + "stop_t2t": 148519738, + "disease": "Neuronal intranuclear inclusion disease, Alzheimer disease and parkinsonism phenotype, Oculopharyngodistal myopathy (OPDM) type 3, hereditary essential tremor type 6", + "inheritance": ["AD"], + "association_type": ["Mendelian"], + "disease_description": "Neuronal intranuclear inclusion disease (NIID) is a very rare multisystem neurodegenerative disorder characterized by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells, and neuronal loss [@mondo:0011327]. Due to overlapping phenotypes and the shared locus, it is unclear whether these four diseases are comorbid, synonymous, or entirely separate.", + "hpo_terms": null, + "prevalence": null, + "prevalence_details": ">400 patients reported in literature [@pmid:37371433]. Found in individuals of East Asian ancestry [@pmid:38876750].", + "age_onset": "Typical: 30-70 [@omim:603472]; Range: 10 [@pmid:37090934] - 78 [@pmid:37305750].", + "age_onset_min": 10.0, + "age_onset_max": 78.0, + "typ_age_onset_min": 30.0, + "typ_age_onset_max": 70.0, + "details": "Benign alleles are less than 38 repeats, while pathogenic alleles contain 66+ repeats [@genereviews:NBK535148]. Intermediate alleles may be associated with a phenotypic spectrum, and even pathogenic cases can have variable phenotype [@pmid:39055960; @pmid:39496005]: NOTCH2NLC expansions have been linked Alzheimer's disease and Parkinson's disease, leading to a potential role in NIID-related disorders [@pmid:31178126]. Age of onset inversely related to allele size [@pmid:38377026]. Motif variation in controls: (AGG)(CGG)n(AGG)0-3(CGG)0-2. GGA and AGC interruptions may influence phenotype [@pmid:34718964]. Interruptions documented: GGA, GGG [@pmid:35245110]; ACCGAGAAGATGCCCGCCCTGC interruption proposed but not confirmed [@pmid:38467784]. Detection may be challenging due to parology between genes: C253572.1, NOTCH2, NOTCH2NL, NBPF14, NBPF19.", + "mechanism": "GoF", + "mechanism_detail": "Polyglycine expansion; may relate to methylation or RNA pathogenicity [@omim:603472; @pmid:36169768; @pmid:38467784]. The polyglycine-containing protein sequesters a key subunit of transcription factor NF-κB in nuclear inclusions, leading to impaired autophagy [@doi:10.1186/s12964-025-02079-1]. Tau pathology is evident, changes in p-tau levels and tau deposition have been reported [@pmid:41539185].", + "year": "2019 [@pmid:31332380]", + "location_in_gene": "5' UTR", + "gene_strand": "+", + "reference_motif_reference_orientation": ["GGC"], + "pathogenic_motif_reference_orientation": ["GGC"], + "benign_motif_reference_orientation": [], + "unknown_motif_reference_orientation": [], + "pathogenic_motif_gene_orientation": ["CGG"], + "benign_motif_gene_orientation": [], + "unknown_motif_gene_orientation": [], + "locus_structure": [], + "benign_min": 7, + "benign_max": 37, + "intermediate_min": 38, + "intermediate_max": 65, + "pathogenic_min": 66, + "pathogenic_max": 517, + "motif_len": 3, + "ref_copies": 13.3, + "novel": "ref", + "gard": ["3971"], + "genereviews": ["NBK535148"], + "malacard": ["NRN008"], + "medgen": ["355075"], + "mondo": ["0011327"], + "omim": ["603472", "619473"], + "orphanet": ["2289"], + "gnomad": ["NOTCH2NLC"], + "stripy": ["NOTCH2NLC"], + "tr_atlas": ["TR7525"], + "webstr_hg38": [], + "webstr_hg19": [], + "locus_tags": ["supported_evidence", "somatic_instability", "paternal_expansion", "length_affects_onset", "length_affects_phenotype", "motif_affects_onset", "motif_affects_phenotype"], + "disease_tags": ["phenotypic_spectrum"], + "references": ["omim:603472", "pmid:37090934", "pmid:37305750", "pmid:36169768", "pmid:38467784", "doi:10.1186/s12964-025-02079-1", "genereviews:NBK535148", "pmid:39055960", "pmid:39496005", "pmid:31178126", "pmid:38377026", "pmid:34718964", "pmid:35245110", "pmid:37371433", "pmid:38876750", "pmid:31332380", "mondo:0011327"], + "additional_literature": ["pmid:41556371", "pmid:41539185", "pmid:41526374", "pmid:41235412", "pmid:41154122", "pmid:41074692", "pmid:40934004", "pmid:40879637", "pmid:40765612", "pmid:40708231", "pmid:40645757", "pmid:40635536", "pmid:40609325", "pmid:40517194", "pmid:40515658", "pmid:40514451", "pmid:40267536", "pmid:40084170", "pmid:39936620", "pmid:39920690", "pmid:39609868", "pmid:39529621", "pmid:39505310", "pmid:39492694", "pmid:39418922", "pmid:39167540", "pmid:39078482", "pmid:38779172", "pmid:38667292", "pmid:38579412", "pmid:38477063", "pmid:38288273", "pmid:38145851", "pmid:37975799", "pmid:37923380", "pmid:37864208", "pmid:37823700", "pmid:37644522", "pmid:37365282", "pmid:37271829", "pmid:37237429", "pmid:37184590", "pmid:37131242", "pmid:37001413", "pmid:36948577", "pmid:36942588", "pmid:36825461", "pmid:36823368", "pmid:36809423", "pmid:36715780", "pmid:36672065", "pmid:36621630", "pmid:36588885", "pmid:36570826", "pmid:36545534", "pmid:36483830", "pmid:36458450", "pmid:36417528", "pmid:36263606", "pmid:36216675", "pmid:36207023", "pmid:36191230", "pmid:36172483", "pmid:36150977", "pmid:36086903", "pmid:36061987", "pmid:36041634", "pmid:36033605", "pmid:35974122", "pmid:35866887", "pmid:35857137", "pmid:35838850", "pmid:35788208", "pmid:35772299", "pmid:35700120", "pmid:35419641", "pmid:35411397", "pmid:35402653", "pmid:35366689", "pmid:35314910", "pmid:35297556", "pmid:35180462", "pmid:35152460", "pmid:35148830", "pmid:35147270", "pmid:34927285", "pmid:34797461", "pmid:34774111", "pmid:34750918", "pmid:34694469", "pmid:34675106", "pmid:34641814", "pmid:34392981", "pmid:34306035", "pmid:34243731", "pmid:34054431", "pmid:34017298", "pmid:33943039", "pmid:33887199", "pmid:33871559", "pmid:33871549", "pmid:33766934", "pmid:33693509", "pmid:33679585", "pmid:33626493", "pmid:33625684", "pmid:33388663", "pmid:33377220", "pmid:33377207", "pmid:33239111", "pmid:33201994", "pmid:33201988", "pmid:33146692", "pmid:33146671", "pmid:33026126", "pmid:33016348", "pmid:32989102", "pmid:32931575", "pmid:32852534", "pmid:32827029", "pmid:32817896", "pmid:32777174", "pmid:32768149", "pmid:32602554", "pmid:32535679", "pmid:32516806", "pmid:32495371", "pmid:32449905", "pmid:32268889", "pmid:32250060", "pmid:32081467", "pmid:32039647", "pmid:31886491", "pmid:31819945", "pmid:31433517", "pmid:31413119", "pmid:31332381"] +}, +{ + "id": "OPML1_NUTM2B-AS1", + "disease_id": "OPML1", + "gene": "NUTM2B-AS1", + "evidence": ["Moderate"], + "chrom": "chr10", + "start_hg38": 79826383, + "stop_hg38": 79826404, + "start_hg19": 81586139, + "stop_hg19": 81586160, + "start_t2t": 80695718, + "stop_t2t": 80695748, + "disease": "Oculopharyngeal myopathy with leukoencephalopathy 1", + "inheritance": ["AD"], + "association_type": ["Mendelian"], + "disease_description": "Oculopharyngodistal myopathy and white matter abnormalities [@pmid:38876750]; Ptosis, ophthalmoplegia, dysphagia, dysarthria [@pmid:39349043].", + "hpo_terms": null, + "prevalence": null, + "prevalence_details": "Rare, found in individuals of East Asian ancestry [@pmid:38876750].", + "age_onset": "15-40 (only characterized in one family) [@pmid:31332380].", + "age_onset_min": 15.0, + "age_onset_max": 40.0, + "typ_age_onset_min": null, + "typ_age_onset_max": null, + "details": "Benign range (3-16 repeats) established in 1000 controls, studied alongside pathogenic probands of up to 700 repeats [@pmid:31332380]. Pathogenicity occurs at repeats as short as 161 motifs [@pmid:38159879; @pmid:37923380], while intermediate alleles may correlate to milder phenotypes [@pmid:38159879]. Alt transcript in opposite direction: LOC642361.", + "mechanism": "GoF?", + "mechanism_detail": "RNA mediated toxicity hypothesized, overall mechanism unknown [@omim:618637; @pmid:36169768].", + "year": "2019 [@pmid:31332380]", + "location_in_gene": "Exon 1 of lncRNA (noncoding)", + "gene_strand": "+", + "reference_motif_reference_orientation": ["GGC"], + "pathogenic_motif_reference_orientation": ["GGC"], + "benign_motif_reference_orientation": [], + "unknown_motif_reference_orientation": [], + "pathogenic_motif_gene_orientation": ["CGG"], + "benign_motif_gene_orientation": [], + "unknown_motif_gene_orientation": [], + "locus_structure": [], + "benign_min": 3, + "benign_max": 16, + "intermediate_min": null, + "intermediate_max": null, + "pathogenic_min": 161, + "pathogenic_max": 700, + "motif_len": 3, + "ref_copies": 7.0, + "novel": "ref", + "gard": [], + "genereviews": ["NBK535148"], + "malacard": ["OCL077"], + "medgen": ["1684701"], + "mondo": ["0032843"], + "omim": ["618637"], + "orphanet": [], + "gnomad": ["NUTM2B-AS1"], + "stripy": ["NUTM2B-AS1"], + "tr_atlas": ["TR102881"], + "webstr_hg38": [], + "webstr_hg19": ["STR_173942"], + "locus_tags": ["supported_evidence", "length_affects_severity", "length_affects_phenotype"], + "disease_tags": [], + "references": ["pmid:31332380", "omim:618637", "pmid:36169768", "pmid:38159879", "pmid:37923380", "pmid:38876750", "pmid:39349043"], + "additional_literature": ["pmid:40645757", "pmid:39308795", "pmid:35152460"] +} +] \ No newline at end of file