HMBS (hydroxymethylbilane synthase)

Gene

• Entrez ID: 3145
• Gene name: Hydroxymethylbilane synthase
• Gene symbol: HMBS
• Synonyms (NCBI Gene): ENCEP, LENCEP, PBG-D, PBGD, PORC, UPS
• Chromosome: 11
• Chromosome location: 11q23.3
• Summary: This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethy

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs34413634	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs118204094	C>T	Pathogenic	Coding sequence variant, missense variant
rs118204095	G>A,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs118204096	G>A	Pathogenic	Coding sequence variant, missense variant
rs118204097	C>T	Pathogenic	Coding sequence variant, stop gained
rs118204098	G>A	Pathogenic	Coding sequence variant, missense variant
rs118204099	T>G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs118204100	G>A	Pathogenic	Coding sequence variant, stop gained
rs118204101	C>T	Pathogenic	Coding sequence variant, missense variant
rs118204103	G>A,T	Likely-pathogenic, pathogenic	Coding sequence variant, intron variant, missense variant
rs118204104	G>A	Pathogenic	Coding sequence variant, 5 prime UTR variant, missense variant
rs118204105	C>A	Pathogenic	Coding sequence variant, 5 prime UTR variant, missense variant
rs118204106	G>T	Pathogenic	Coding sequence variant, 5 prime UTR variant, missense variant
rs118204107	G>A	Pathogenic	Coding sequence variant, missense variant
rs118204108	T>G	Pathogenic	Coding sequence variant, missense variant
rs118204109	C>T	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs118204110	G>A	Likely-pathogenic	Coding sequence variant, intron variant, missense variant
rs118204111	T>C	Pathogenic	Coding sequence variant, intron variant, missense variant
rs118204112	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant
rs118204113	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant
rs118204114	C>T	Pathogenic	Coding sequence variant, intron variant, missense variant
rs118204115	C>A,G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs118204116	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs118204117	G>A,C	Pathogenic	Coding sequence variant, stop gained, missense variant
rs118204118	A>G	Pathogenic	Missense variant, genic upstream transcript variant, initiator codon variant, 5 prime UTR variant
rs118204119	T>C	Pathogenic	Coding sequence variant, missense variant
rs118204120	C>T	Pathogenic	Coding sequence variant, stop gained
rs150428209	G>A,C,T	Benign-likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs201349602	A>C,G	Benign, conflicting-interpretations-of-pathogenicity	5 prime UTR variant, genic upstream transcript variant
rs536814318	G>A	Likely-pathogenic, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs575222284	C>T	Pathogenic	Coding sequence variant, missense variant
rs767103817	G>A,T	Likely-pathogenic	Coding sequence variant, intron variant, missense variant
rs974712040	C>T	Likely-pathogenic	Coding sequence variant, missense variant, 5 prime UTR variant
rs998842815	C>T	Pathogenic	Intron variant, coding sequence variant, missense variant
rs1057518806	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057518886	C>-	Pathogenic	Stop gained, coding sequence variant
rs1057521126	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1165046276	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1285037788	CT>-	Pathogenic	Frameshift variant, coding sequence variant
rs1286913162	G>A	Pathogenic	Splice acceptor variant
rs1325031228	C>T	Pathogenic	Stop gained, coding sequence variant, intron variant
rs1555206128	AGTGCGAGCCAAGGACCAGGACATCTTGGA>-	Pathogenic	Coding sequence variant, inframe deletion, intron variant
rs1555206402	GCCCATTAACTGGTTTGTGGGGCACAGATGCCTGGGTTGCTGCTGTCCAGTGCCT>-	Pathogenic	Terminator codon variant, frameshift variant, 3 prime UTR variant
rs1565750784	G>A,T	Pathogenic	Splice donor variant, 5 prime UTR variant, genic upstream transcript variant
rs1565754285	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1565754296	->G	Pathogenic	Coding sequence variant, frameshift variant
rs1565754452	G>A	Pathogenic	Splice acceptor variant
rs1565754565	G>C	Pathogenic	Splice donor variant
rs1565756481	G>A	Pathogenic	Splice acceptor variant
rs1565757839	CT>-	Pathogenic	Coding sequence variant, frameshift variant, intron variant
rs1565757857	->TTCGCTGC	Pathogenic	Coding sequence variant, frameshift variant, intron variant
rs1565758008	G>C	Pathogenic	Splice donor variant, intron variant
rs1565758795	->T	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1565758825	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1592212904	A>-	Pathogenic	Intron variant, 5 prime UTR variant, frameshift variant, coding sequence variant
rs1592213590	G>C	Pathogenic	Intron variant
rs1592214208	GT>-	Pathogenic	Initiator codon variant, frameshift variant, coding sequence variant
rs1592214498	GA>-	Pathogenic	Frameshift variant, coding sequence variant
rs1592215117	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1592215837	C>T	Pathogenic	Coding sequence variant, stop gained
rs1592217625	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1592217645	->G	Pathogenic	Frameshift variant, coding sequence variant
rs1592217847	G>T	Pathogenic	Missense variant, coding sequence variant
rs1592217853	G>A	Pathogenic	Splice donor variant
rs1592219635	A>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs1592219658	A>G	Likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs1592220835	TG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1592220915	C>T	Pathogenic	Coding sequence variant, stop gained
rs1592221672	T>-	Likely-pathogenic	Frameshift variant, terminator codon variant, stop lost

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT050301	hsa-miR-25-3p	CLASH	23622248
MIRT1048861	hsa-miR-181a	CLIP-seq
MIRT1048862	hsa-miR-181b	CLIP-seq
MIRT1048863	hsa-miR-181c	CLIP-seq
MIRT1048864	hsa-miR-181d	CLIP-seq
MIRT1048865	hsa-miR-3159	CLIP-seq
MIRT1048866	hsa-miR-409-5p	CLIP-seq
MIRT1048867	hsa-miR-4262	CLIP-seq
MIRT1048868	hsa-miR-4687-3p	CLIP-seq
MIRT1048869	hsa-miR-509-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004418	Function	Hydroxymethylbilane synthase activity	IBA
GO:0004418	Function	Hydroxymethylbilane synthase activity	IDA	18004775, 18936296
GO:0004418	Function	Hydroxymethylbilane synthase activity	IEA
GO:0004418	Function	Hydroxymethylbilane synthase activity	TAS	2025226
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	ISS
GO:0005829	Component	Cytosol	TAS
GO:0006779	Process	Porphyrin-containing compound biosynthetic process	IEA
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IDA	18004775
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	IBA
GO:0006783	Process	Heme biosynthetic process	IC	18004775
GO:0006783	Process	Heme biosynthetic process	IDA	18936296
GO:0006783	Process	Heme biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	TAS
GO:0006784	Process	Heme A biosynthetic process	IEA
GO:0006785	Process	Heme B biosynthetic process	IDA	18004775
GO:0006785	Process	Heme B biosynthetic process	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0033014	Process	Tetrapyrrole biosynthetic process	IEA
GO:0048034	Process	Heme O biosynthetic process	IEA

Other IDs

• MIM: 609806
• HGNC: 4982
• e!Ensembl: ENSG00000256269

Protein

• UniProt ID: P08397
• Protein name: Porphobilinogen deaminase (PBG-D) (EC 2.5.1.61) (Hydroxymethylbilane synthase) (HMBS) (Pre-uroporphyrinogen synthase)
• Protein function: As part of the heme biosynthetic pathway, catalyzes the sequential polymerization of four molecules of porphobilinogen to form hydroxymethylbilane, also known as preuroporphyrinogen (PubMed:18004775, PubMed:18936296, PubMed:19138865, PubMed:2381
• PDB: 3ECR, 3EQ1, 5M6R, 5M7F, 7AAJ, 7AAK, 7CCX, 7CCY, 7CCZ, 7CD0, 8PND
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01379	Porphobil_deam	21 → 233	Porphobilinogen deaminase, dipyromethane cofactor binding domain	Domain
  PF03900	Porphobil_deamC	244 → 322	Porphobilinogen deaminase, C-terminal domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: [Isoform 1]: Is ubiquitously expressed. {ECO:0000269|PubMed:3422427}.; TISSUE SPECIFICITY: [Isoform 2]: Is found only in erythroid cells. {ECO:0000269|PubMed:3422427}.
• Sequence:

  MSGNGNAAATAEENSPKMRVIRVGTRKSQLARIQTDSVVATLKASYPGLQFEIIAMSTTG
  DKILDTALSKIGEKSLFTKELEHALEKNEVDLVVHSLKDLPTVLPPGFTIGAICKRENPH
  DAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDEQ
  QEFSAIILATAGLQRMGWHNRVGQILHPEECMYAVGQGALGVEVRAKDQDILDLVGVLHD
  PETLLRCIAERAFLRHLEGGCSVPVAVHTAMKDGQLYLTGGVWSLDGSDSIQETMQATIH
  VPAQHEDGPEDDPQLVGITARNIPRGPQLAAQNLGISLANLLLSKGAKNILDVARQLNDA
  H

• Sequence length: 361

Pathways

KEGG:

Porphyrin metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Heme biosynthesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abdominal pain	Pathogenic; Likely pathogenic	rs1057518886, rs1057518806	RCV000415135 RCV000415138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Abnormal circulating porphyrin concentration	Pathogenic	rs1592217625	RCV001003599	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Acute episodes of neuropathic symptoms	Likely pathogenic	rs1057518806	RCV000415138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Acute intermittent porphyria	Likely pathogenic; Pathogenic	rs1946187914, rs1946317952, rs2134885779, rs2134859316, rs1565754452, rs118204095, rs118204103, rs118204094, rs118204096, rs118204097, rs118204098, rs118204099, rs1565758825, rs118204100, rs118204104, rs118204105, rs118204101, rs1565754285, rs1565754296, rs118204107, rs1565756481, rs118204108, rs1565757839, rs118204111, rs1565757857, rs118204112, rs118204114, rs118204115, rs1565758008, rs1946325053, rs1565754565, rs118204116, rs1592220835, rs118204117, rs118204120, rs2134859037, rs2497475732, rs34413634, rs2497452998, rs2497472277, rs2497453440, rs2134876594, rs2497440458, rs2497471386, rs2497396935, rs1057518886, rs974712040, rs1555206128, rs1555206402, rs1565758795, rs998842815, rs1592214498, rs575222284, rs1592217847, rs1325031228, rs1592220915, rs1286913162, rs1592213590, rs770086296, rs143984293, rs771206317	RCV001332261 RCV001332263 RCV002246365 RCV001786486 RCV001789607 RCV005042682 RCV000001508 RCV000001510 RCV000001511 RCV000001512 RCV000001513 RCV000001514 RCV000001515 RCV000001516 RCV000001518 RCV000001519 RCV000001520 RCV000001521 RCV000001522 RCV000001524 RCV000001525 RCV000001526 RCV000001529 RCV000001530 RCV000001531 RCV000001533 RCV000001534 RCV000001535 RCV000001536 RCV000001538 RCV000001539 RCV000001540 RCV000001541 RCV000001542 RCV000001543 RCV000001544 RCV000001548 RCV000001551 RCV002225205 RCV002293282 RCV000148509 RCV003319952 RCV003333896 RCV003334474 RCV003445455 RCV004818379 RCV003990487 RCV003994651 RCV004594970 RCV001197501 RCV001254080 RCV000625717 RCV000664186 RCV000755705 RCV003152734 RCV002280823 RCV001198558 RCV002249519 RCV005253130 RCV003152735 RCV005407999 RCV000855547 RCV001535464 RCV001171316 RCV001198011	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Anxiety	Likely pathogenic	rs1057518806	RCV000415138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Elevated urinary delta-aminolevulinic acid	Likely pathogenic	rs1057518806	RCV000415138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Emotional lability	Pathogenic	rs1057518886	RCV000415135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Encephalopathy, porphyria-related	Likely pathogenic; Pathogenic	rs118204095, rs118204096, rs118204101, rs118204119	RCV005042682 RCV003764509 RCV003764511 RCV003764512 RCV003764513	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Fever	Pathogenic	rs1057518886	RCV000415135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hepatocellular carcinoma	Pathogenic	rs2134884322, rs1565750784	RCV005912657 RCV005887193	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HMBS-related disorder	Likely pathogenic; Pathogenic	rs1946317952, rs118204120, rs575222284, rs1325031228	RCV003983876 RCV003924793 RCV004748972 RCV003908095	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukoencephalopathy, porphyria-related	Likely pathogenic; Pathogenic	rs118204095, rs1946174844	RCV005042682 RCV003764510 RCV003881685	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Malignant tumor of urinary bladder	Pathogenic	rs782201645	RCV005909028	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian serous cystadenocarcinoma	Pathogenic	rs1565754565	RCV005924375	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Porphyria, acute intermittent, nonerythroid variant	Pathogenic	rs1565750784, rs2497394478, rs1592212904	RCV000001506 RCV000001509 RCV000001546 RCV000001547	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Visual loss	Pathogenic	rs1057518886	RCV000415135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Vomiting	Pathogenic	rs1057518886	RCV000415135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA, SICKLE CELL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1J	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISORDERS OF GLYCOSYLATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL ARTERIAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PORPHYRIA, ACUTE INTERMITTENT	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute intermittent porphyria	Intermittent Porphyria	BEFREE	10207164, 10408772, 10416826, 10453740, 10494093, 10502788, 10602775, 10657149, 10667475, 10782018, 10790212, 10944860, 11013452, 11030413, 11055586, 11071386, 11185747, 11202057, 11399210, 11591889, 1165472, 11831862, 11857754, 11940707, 12004925, 12372055, 12406973, 12566739, 12699245, 12899439, 12962144, 1301948, 14757946, 1496994, 14995910, 15208740, 15469427, 15534187, 1588264, 16025832, 16211556, 1679034, 16828319, 16935474, 17298216, 1733614, 17654633, 18070416, 18406650, 18627369, 18669508, 18936296, 19138865, 19207107, 19267997, 19292878, 1961762, 19656452, 19656453, 1973402, 19815305, 19861948, 19934113, 20850424, 20877347, 20978940, 21855406, 2243128, 22748422, 2303246, 23562909, 23815679, 24070415, 2511016, 25445397, 2563167, 25703257, 25787008, 25870942, 25923088, 25979770, 26071363, 26075277, 27558376, 27769855, 27849156, 2789372, 28011390, 28666226, 28990424, 2900803, 29317194, 29360981, 29476795, 29498764, 29632172, 30085095, 30201327, 30212967, 30218352, 30297912, 30528119, 30615115, 30639047, 30737139, 30740734, 30777612, 30808393, 31044425, 31269991, 31572191, 31810863, 3783903, 3928029, 4522787, 458830, 621286, 6517099, 6652953, 7258864, 7592566, 7592571, 7623445, 7635464, 7757070, 7849582, 7866402, 7891051, 7891052, 7962538, 8023693, 8070086, 8081367, 8096492, 8168829, 8168833, 8222280, 8262523, 8270254, 8270256, 8533808, 8563760, 8684377, 8733062, 8825929, 8860014, 9067752, 9162306, 9225970, 9238757, 9281416, 9350165, 9371741, 9455613, 9463797, 9633040, 9654202, 9860299		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute intermittent porphyria	Intermittent Porphyria	UNIPROT_DG	10453740, 10494093, 10502788, 10602775, 10657149, 10782018, 11013452, 11030413, 11399210, 11857754, 12372055, 12406973, 12773194, 1301948, 1427766, 14669009, 14757946, 1496994, 14970743, 15669678, 16211556, 1714233, 18406650, 19138865, 19292878, 2243128, 23815679, 25703257, 25870942, 7757070, 7962538, 8081367, 8262523, 8268934, 8270254, 8270256, 8401516, 8825929, 9199558, 9225970, 9463797, 9654202		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute intermittent porphyria	Intermittent Porphyria	LHGDN	11399210, 11831862, 11857754, 11940707, 15669678, 16211556, 16817012, 17298216, 17298217, 18405488, 18627369, 18936296		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute intermittent porphyria	Intermittent Porphyria	CLINVAR_DG	12372055, 26075277, 7962538, 8270256		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute intermittent porphyria	Intermittent Porphyria	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute intermittent porphyria	Intermittent Porphyria	GENOMICS_ENGLAND_DG	27604308		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute intermittent porphyria	Intermittent Porphyria	CTD_human_DG	6132132, 8772850		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Adenoma	Adenoma	BEFREE	24135907		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	19477221	Associate	★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	27743375		★☆☆☆☆ Found in Text Mining only
Anorexia	Anorexia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Anxiety	Anxiety Disorder	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Breast Carcinoma	Breast Carcinoma	BEFREE	20008677		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	35636578	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	19036168, 23811755, 35636578	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	36409970	Associate	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	BEFREE	7891052		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cirrhosis	Cirrhosis	BEFREE	7891052		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	30186311		★☆☆☆☆ Found in Text Mining only
Coproporphyria Hereditary	Hereditary coproporphyria	Pubtator	19460837, 31073229	Associate	★☆☆☆☆ Found in Text Mining only
Cranial nerve palsies	Cranial Nerve Paralysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	18047735		★☆☆☆☆ Found in Text Mining only
Deficiency of Uroporphyrinogen III Synthase	Deficiency Of Uroporphyrinogen III Synthase	BEFREE	9164637		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	23246353		★☆☆☆☆ Found in Text Mining only
Disorders of Porphyrin Metabolism	Porphyria	BEFREE	12699245, 1588264, 18406650, 20877347, 23562909, 621286		★☆☆☆☆ Found in Text Mining only
Disorders of Porphyrin Metabolism	Porphyria	LHGDN	16390615, 17298217		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	27558376		★☆☆☆☆ Found in Text Mining only
Endometrial Stromal Sarcoma	Endometrial Stromal Sarcoma	BEFREE	22266404		★☆☆☆☆ Found in Text Mining only
Erythropoietic Protoporphyria	Erythropoietic Protoporphyria	BEFREE	12699245		★☆☆☆☆ Found in Text Mining only
Follicular thyroid carcinoma	Follicular Thyroid Carcinoma	BEFREE	16091757		★☆☆☆☆ Found in Text Mining only
Frontotemporal dementia	Frontotemporal dementia	BEFREE	19884572		★☆☆☆☆ Found in Text Mining only
Frontotemporal Lobar Degeneration	Frontotemporal dementia	BEFREE	19884572, 20490813, 22355793		★☆☆☆☆ Found in Text Mining only
Gilles de la Tourette syndrome	Tourette Syndrome	BEFREE	1978653		★☆☆☆☆ Found in Text Mining only
Hallucinations	Hallucinations	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	30186311		★☆☆☆☆ Found in Text Mining only
Hepatitis C	Hepatitis c	Pubtator	27193023	Associate	★☆☆☆☆ Found in Text Mining only
Homocystinuria	Homocystinuria	Pubtator	6940198	Associate	★☆☆☆☆ Found in Text Mining only
Hydroxymethylbilane Synthase Deficiency	Hydroxymethylbilane Synthase Deficiency	BEFREE	23562909		★☆☆☆☆ Found in Text Mining only
Hydroxymethylbilane Synthase Deficiency	Hydroxymethylbilane Synthase Deficiency	CTD_human_DG	6132132, 8772850		★☆☆☆☆ Found in Text Mining only
Hyperlipidemia	Hyperlipidemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	30184115		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	18929575		★☆☆☆☆ Found in Text Mining only
Hyperuricemia	Hyperuricemia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypoxic-Ischemic Encephalopathy	Hypoxic-Ischemic Encephalopathy	BEFREE	12444904		★☆☆☆☆ Found in Text Mining only
Idiopathic pulmonary arterial hypertension	Pulmonary arterial hypertension	BEFREE	28212825		★☆☆☆☆ Found in Text Mining only
Inborn Errors of Metabolism	Inborn Errors Of Metabolism	BEFREE	7866402, 8533808		★☆☆☆☆ Found in Text Mining only
Laryngeal cleft	Laryngeal cleft	BEFREE	7891052		★☆☆☆☆ Found in Text Mining only
Laryngeal Neoplasms	Laryngeal neoplasm	Pubtator	31173291	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	1384662, 1824246		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	36595475	Associate	★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	27558376		★☆☆☆☆ Found in Text Mining only
Liddle Syndrome	Liddle Syndrome	BEFREE	19007435		★☆☆☆☆ Found in Text Mining only
Lipoid nephrosis	Lipoid Nephrosis	BEFREE	24722446		★☆☆☆☆ Found in Text Mining only
liposarcoma	Liposarcoma	BEFREE	25906748		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	25445397, 7891052		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	7891052		★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	38068980	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	1384662		★☆☆☆☆ Found in Text Mining only
Machado-Joseph Disease	Machado-Joseph Disease	BEFREE	29427114		★☆☆☆☆ Found in Text Mining only
Malignant Fibrous Histiocytoma	Malignant Histiocytoma	BEFREE	29481803		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	20008677		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	25445397		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31374232, 7891052		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	16211556, 23562909, 26071363, 31269991		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	30851297		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	8918822		★☆☆☆☆ Found in Text Mining only
Myofibrillar Myopathy	Myofibrillar myopathy	BEFREE	17784878		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10483361, 16458257, 20008677, 25445397, 7891052, 9162306		★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic Syndrome	BEFREE	24722446		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	18937340, 31048127		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	21855406		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	28857503		★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	BEFREE	16091757		★☆☆☆☆ Found in Text Mining only
Paralytic Ileus	Paralytic Ileus	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Paralytic Ileus	Paralytic Ileus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pelger-Huet Anomaly	Pelger-Huet Anomaly	BEFREE	3678479		★☆☆☆☆ Found in Text Mining only
Peripheral motor neuropathy	Motor nerve neuritis	BEFREE	10207164, 11940707		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	10207164		★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	10207164		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	28761164	Associate	★☆☆☆☆ Found in Text Mining only
Porphobilinogen synthase deficiency	Porphobilinogen Synthase Deficiency	BEFREE	8024730		★☆☆☆☆ Found in Text Mining only
Porphyria Acute Hepatic	Porphyria	Pubtator	31073229, 40186107	Associate	★☆☆☆☆ Found in Text Mining only
Porphyria Acute Intermittent	Porphyria	Pubtator	10602775, 11399210, 11591889, 14757946, 1496994, 16935474, 1714233, 17298217, 17298218, 19292878, 19460837, 1961762, 21532227, 21618697, 2243128, 23650938, 23815679, 2563167, 25923088, 26062020, 27539938, 2789372, 28025645, 29632172, 30071891, 30212967, 30740734, 31073229, 31269991, 32306994, 32558425, 32806544, 33275677, 34681668, 35636578, 35762500, 36115019, 36329616, 37729906, 37863644, 3816774, 3928029, 39948482, 40551442, 4522787, 621286, 7251856, 7962538, 8733062, 8825929, 9199558, 9350165, 9371741	Associate	★☆☆☆☆ Found in Text Mining only
Porphyria Acute Intermittent	Porphyria	Pubtator	1165472, 19292878, 27788171, 5056653	Inhibit	★☆☆☆☆ Found in Text Mining only
Porphyria Variegate	Variegate porphyria	Pubtator	11800145	Inhibit	★☆☆☆☆ Found in Text Mining only
Porphyria Variegate	Variegate porphyria	Pubtator	31073229	Associate	★☆☆☆☆ Found in Text Mining only
Porphyria, Acute Intermittent, Nonerythroid Variant	Porphyria	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Porphyria, Erythropoietic	Congenital erythropoietic porphyria	BEFREE	19934113		★☆☆☆☆ Found in Text Mining only
Porphyrias	Porphyria	Pubtator	2497768	Associate	★☆☆☆☆ Found in Text Mining only
Porphyrias, Hepatic	Hepatic porphyria	LHGDN	14669009		★☆☆☆☆ Found in Text Mining only
Porphyrias, Hepatic	Hepatic porphyria	BEFREE	17298218		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	36095024	Associate	★☆☆☆☆ Found in Text Mining only
Psychotic episodes	Psychosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Psychotic episodes	Psychosis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	1358185, 1358782, 2069495, 28226265, 8094629, 8439242, 8475213		★☆☆☆☆ Found in Text Mining only
Seminoma	Seminoma	BEFREE	15823405		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	19650912	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	16091757	Associate	★☆☆☆☆ Found in Text Mining only
Tuberous Sclerosis	Tuberous Sclerosis	BEFREE	2769723		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	33057113	Associate	★☆☆☆☆ Found in Text Mining only
Variegate Porphyria	Variegate Porphyria	BEFREE	12699245, 25445397, 2864531, 3015635		★☆☆☆☆ Found in Text Mining only