Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	3145
Gene name	Hydroxymethylbilane synthase
Gene symbol	HMBS
Synonyms (NCBI Gene)	ENCEPLENCEPPBG-DPBGDPORCUPS
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

Show/Hide all (69)

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

Show/Hide all (10)

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

Show/Hide all (25)

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

MIM	HGNC	e!Ensembl
609806	4982	ENSG00000256269

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

Interactions

View interactions

	KEGG		Reactome
	Porphyrin metabolism Metabolic pathways Biosynthesis of cofactors		Heme biosynthesis

211

Show/Hide Causal Diseases (17)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Abdominal pain	Pathogenic; Likely pathogenic	rs1057518886, rs1057518806	RCV000415135 RCV000415138
Abnormal circulating porphyrin concentration	Pathogenic	rs1592217625	RCV001003599
Acute episodes of neuropathic symptoms	Likely pathogenic	rs1057518806	RCV000415138
Acute intermittent porphyria	Likely pathogenic; Pathogenic	rs1946187914, rs1946317952, rs2134885779, rs2134859316, rs1565754452, rs118204095, rs118204103, rs118204094, rs118204096, rs118204097, rs118204098, rs118204099, rs1565758825, rs118204100, rs118204104 View all (46 more)	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
Anxiety	Likely pathogenic	rs1057518806	RCV000415138
Elevated urinary delta-aminolevulinic acid	Likely pathogenic	rs1057518806	RCV000415138
Emotional lability	Pathogenic	rs1057518886	RCV000415135
Encephalopathy, porphyria-related	Likely pathogenic; Pathogenic	rs118204095, rs118204096, rs118204101, rs118204119	RCV005042682 RCV003764509 RCV003764511 RCV003764512 RCV003764513
Fever	Pathogenic	rs1057518886	RCV000415135
Hepatocellular carcinoma	Pathogenic	rs2134884322, rs1565750784	RCV005912657 RCV005887193
HMBS-related disorder	Likely pathogenic; Pathogenic	rs1946317952, rs118204120, rs575222284, rs1325031228	RCV003983876 RCV003924793 RCV004748972 RCV003908095
Leukoencephalopathy, porphyria-related	Likely pathogenic; Pathogenic	rs118204095, rs1946174844	RCV005042682 RCV003764510 RCV003881685
Malignant tumor of urinary bladder	Pathogenic	rs782201645	RCV005909028
Ovarian serous cystadenocarcinoma	Pathogenic	rs1565754565	RCV005924375
Porphyria, acute intermittent, nonerythroid variant	Pathogenic	rs1565750784, rs2497394478, rs1592212904	RCV000001506 RCV000001509 RCV000001546 RCV000001547
Visual loss	Pathogenic	rs1057518886	RCV000415135
Vomiting	Pathogenic	rs1057518886	RCV000415135

Show/Hide Unknown Diseases (10)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute myeloid leukemia	Benign; Likely benign	rs28990986, rs373396982	RCV005924512 RCV005928455
Cervical cancer	Benign	rs199862927	RCV005926264
Cholangiocarcinoma	Benign	rs28990986	RCV005924516
Familial cancer of breast	Benign	rs199862927	RCV005926263
Sarcoma	Benign	rs199862927	RCV005926265
Thymoma	Benign	rs28990986	RCV005924515
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	rs150763621	RCV005888286
Uterine carcinosarcoma	Benign	rs28990986	RCV005924514
Uterine corpus endometrial carcinoma	Benign; Conflicting classifications of pathogenicity	rs199862927, rs150763621	RCV005926266 RCV005888287
Uveal melanoma	Benign	rs28990986	RCV005924513

Show/Hide Text Mining Associations (31)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Alzheimer Disease	Associate	19477221
Carcinogenesis	Associate	35636578
Carcinoma Hepatocellular	Associate	19036168, 23811755, 35636578
Carcinoma Pancreatic Ductal	Associate	36409970
Coproporphyria Hereditary	Associate	19460837, 31073229
Emanuel syndrome	Associate	1824246
Genetic Diseases Inborn	Associate	17298217
Hepatitis C	Associate	27193023
Heredodegenerative Disorders Nervous System	Associate	37729906
Homocystinuria	Associate	6940198
Hypopharyngeal Neoplasms	Associate	31173291
Laryngeal Neoplasms	Associate	31173291
Lateral meningocele syndrome	Associate	23825676
Leukemia	Associate	36595475
Liver Diseases	Associate	38068980
Neoplasms	Associate	19036168, 19650912, 35636578
Niemann Pick Disease Type A	Associate	29632172
Plaque Amyloid	Associate	27743375
Polycystic Ovary Syndrome	Associate	28761164
Porphyria Acute Hepatic	Associate	31073229, 40186107
Porphyria Acute Intermittent	Associate	10602775, 11399210, 11591889, 14757946, 1496994, 16935474, 1714233, 17298217, 17298218, 19292878, 19460837, 1961762, 21532227, 21618697, 2243128 View all (38 more)
Porphyria Acute Intermittent	Inhibit	1165472, 19292878, 27788171, 5056653
Porphyria Chester type	Associate	17298217
Porphyria Variegate	Inhibit	11800145
Porphyria Variegate	Associate	31073229
Porphyrias	Associate	2497768
Posterior Leukoencephalopathy Syndrome	Associate	32306994
Prostatic Neoplasms	Associate	36095024
Squamous Cell Carcinoma of Head and Neck	Associate	19650912
Thyroid Cancer Papillary	Associate	16091757
Urinary Bladder Neoplasms	Associate	33057113

HMBS (hydroxymethylbilane synthase)