HMBS (hydroxymethylbilane synthase)

Gene

• Entrez ID: 3145
• Gene name: Hydroxymethylbilane synthase
• Gene symbol: HMBS
• Synonyms: 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	21873635
GO:0004418	Function	Hydroxymethylbilane synthase activity	IDA	18004775
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	IBA	21873635
GO:0006783	Process	Heme biosynthetic process	IC	18004775
GO:0006783	Process	Heme biosynthetic process	TAS
GO:0018160	Process	Peptidyl-pyrromethane cofactor linkage	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

• 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

Causal
Disease name	Disease term	dbSNP ID	References
Hyperlipidemia	Hyperlipidemia	rs118204057, rs118204060, rs118204062, rs1563569634, rs118204069, rs118204070, rs118204071, rs3737787, rs2073658, rs1566946168, rs1064797075
Hypertension	Hypertensive disease	rs13306026, rs13333226
Intermittent porphyria	Acute intermittent porphyria	rs118204103, rs118204094, rs118204095, rs118204096, rs118204097, rs118204098, rs118204099, rs1565758825, rs118204100, rs118204104, rs118204105, rs118204101, rs1565754285, rs1565754296, rs1565754452, rs118204109, rs118204107, rs1565756481, rs118204108, rs1565757839, rs118204111, rs1565757857, rs118204112, rs118204114, rs118204115, rs1565758008, rs1946325053, rs1565754565, rs118204116, rs1592220835, rs118204117, rs118204120, rs34413634, rs1057518886, rs974712040, rs1555206128, rs1555206402, rs1565758795, rs998842815, rs1592214498, rs575222284, rs1592217847, rs1325031228, rs1592220915, rs1286913162, rs1592213590, rs770086296	16211556, 1496994, 10453740, 10782018, 8270256, 8401516, 14970743, 11857754, 8081367, 12372055, 12773194, 10657149, 6132132, 7962538, 19138865, 26075277, 8825929, 10502788, 8270254, 11399210, 11013452, 10494093, 8262523, 23815679, 14757946, 10602775, 8268934, 1427766, 11030413, 1714233, 14669009, 12406973, 8772850, 15669678, 9463797, 9654202, 19292878, 1301948, 7757070, 25870942, 25703257, 2243128, 18406650, 9199558, 9225970, 27604308
Porphyria	Porphyria, Acute Intermittent, Nonerythroid Variant	rs1565750784, rs1592212904
Renal insufficiency	Renal Insufficiency	rs1596536873

Unknown
Disease name	Disease term	dbSNP ID	References
Anorexia	Anorexia
Anxiety disorder	Anxiety
Cranial nerve paralysis	Cranial nerve palsies
Hallucinations	Hallucinations
Hydroxymethylbilane synthase deficiency	Hydroxymethylbilane Synthase Deficiency		6132132, 8772850
Hyperuricemia	Hyperuricemia
Liver carcinoma	Liver carcinoma
Mental depression	Depressive disorder	rs587778876, rs587778877
Paralytic ileus	Paralytic Ileus
Psychosis	Psychotic episodes