UROS (uroporphyrinogen III synthase)

Gene

• Entrez ID: 7390
• Gene name: Uroporphyrinogen III synthase
• Gene symbol: UROS
• Synonyms: Mgu, UROIIIS
• Chromosome: 10
• Chromosome location: 10q26.2
• Summary: The protein encoded by this gene catalyzes the fourth step of porphyrin biosynthesis in the heme biosynthetic pathway. Defects in this gene cause congenital erythropoietic porphyria (Gunther`s disease). [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28941774	G>A	Pathogenic	Intron variant, coding sequence variant, missense variant, non coding transcript variant
rs28941775	T>C	Pathogenic	Intron variant, coding sequence variant, missense variant, non coding transcript variant
rs121908012	A>C,G	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121908013	G>A	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121908014	G>A	Pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant, intron variant
rs121908015	G>A	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121908017	C>A,T	Pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant
rs121908018	T>A	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121908020	C>T	Pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant, intron variant
rs121908021	G>T	Pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant, intron variant
rs373864821	C>T	Pathogenic	Splice donor variant, intron variant
rs397515349	C>T	Pathogenic	Intron variant
rs397515350	G>T	Pathogenic	Intron variant
rs397515351	G>T	Pathogenic	Intron variant
rs397515527	A>G	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, missense variant
rs397515528	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs750180293	A>C	Pathogenic	Genic downstream transcript variant, intron variant
rs796051859	->C	Pathogenic	Coding sequence variant, intron variant, genic downstream transcript variant, non coding transcript variant, splice acceptor variant
rs1590007244	T>C	Pathogenic	Coding sequence variant, intron variant, non coding transcript variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT038712	hsa-miR-29b-2-5p	CLASH	23622248
MIRT038712	hsa-miR-29b-2-5p	CLASH	23622248
MIRT665541	hsa-miR-6890-3p	HITS-CLIP	23824327
MIRT665540	hsa-miR-6736-3p	HITS-CLIP	23824327
MIRT665539	hsa-miR-221-5p	HITS-CLIP	23824327
MIRT665538	hsa-miR-8073	HITS-CLIP	23824327
MIRT665537	hsa-miR-1304-3p	HITS-CLIP	23824327
MIRT665536	hsa-miR-6787-3p	HITS-CLIP	23824327
MIRT665535	hsa-miR-4772-3p	HITS-CLIP	23824327
MIRT665534	hsa-miR-4695-3p	HITS-CLIP	23824327
MIRT665534	hsa-miR-4695-3p	PAR-CLIP	27292025
MIRT665536	hsa-miR-6787-3p	PAR-CLIP	27292025
MIRT665541	hsa-miR-6890-3p	HITS-CLIP	23824327
MIRT665540	hsa-miR-6736-3p	HITS-CLIP	23824327
MIRT665539	hsa-miR-221-5p	HITS-CLIP	23824327
MIRT665538	hsa-miR-8073	HITS-CLIP	23824327
MIRT665537	hsa-miR-1304-3p	HITS-CLIP	23824327
MIRT665536	hsa-miR-6787-3p	HITS-CLIP	23824327
MIRT665535	hsa-miR-4772-3p	HITS-CLIP	23824327
MIRT665534	hsa-miR-4695-3p	HITS-CLIP	23824327
MIRT1477097	hsa-miR-1285	CLIP-seq
MIRT1477098	hsa-miR-3074-5p	CLIP-seq
MIRT1477099	hsa-miR-3187-5p	CLIP-seq
MIRT1477100	hsa-miR-3667-3p	CLIP-seq
MIRT1477101	hsa-miR-370	CLIP-seq
MIRT1477102	hsa-miR-4731-5p	CLIP-seq
MIRT1477103	hsa-miR-612	CLIP-seq
MIRT1477104	hsa-miR-617	CLIP-seq
MIRT2364002	hsa-miR-2115	CLIP-seq
MIRT2364003	hsa-miR-320e	CLIP-seq
MIRT2364004	hsa-miR-3616-3p	CLIP-seq
MIRT2364005	hsa-miR-3692	CLIP-seq
MIRT2364006	hsa-miR-4436b-3p	CLIP-seq
MIRT2364007	hsa-miR-4503	CLIP-seq
MIRT2364008	hsa-miR-4704-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004852	Function	Uroporphyrinogen-III synthase activity	IBA	21873635
GO:0004852	Function	Uroporphyrinogen-III synthase activity	IDA	3174619, 3805019, 18004775
GO:0004852	Function	Uroporphyrinogen-III synthase activity	TAS
GO:0005739	Component	Mitochondrion	ISS
GO:0005829	Component	Cytosol	NAS	3805019
GO:0005829	Component	Cytosol	TAS
GO:0006780	Process	Uroporphyrinogen III biosynthetic process	IBA	21873635
GO:0006780	Process	Uroporphyrinogen III biosynthetic process	IDA	3174619, 3805019, 18004775
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	IDA	3805019
GO:0006783	Process	Heme biosynthetic process	TAS

Other IDs

• MIM: 606938
• HGNC: 12592
• e!Ensembl: ENSG00000188690

Protein

• UniProt ID: P10746
• Protein name: Uroporphyrinogen-III synthase (UROIIIS) (UROS) (EC 4.2.1.75) (Hydroxymethylbilane hydrolyase [cyclizing]) (Uroporphyrinogen-III cosynthase)
• Protein function: Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins (PubMed:11689424, PubMed:18004775). Porphyr
• PDB: 1JR2
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02602	HEM4	17 → 253	Uroporphyrinogen-III synthase HemD	Family

• Sequence:

  MKVLLLKDAKEDDCGQDPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLI
  FTSPRAVEAAELCLEQNNKTEVWERSLKEKWNAKSVYVVGNATASLVSKIGLDTEGETCG
  NAEKLAEYICSRESSALPLLFPCGNLKREILPKALKDKGIAMESITVYQTVAHPGIQGNL
  NSYYSQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKFAAIGPTTARALAAQGLPVS
  CTAESPTPQALATGIRKALQPHGCC

• Sequence length: 265

Pathways

KEGG:

Porphyrin metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Heme biosynthesis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Hemolytic	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Cholelithiasis	Cholelithiasis	rs121918440, rs72552778, rs387906528, rs759202962, rs377160065, rs1051861187, rs757693457, rs752563752
Hydrops fetalis	Hydrops Fetalis, Non-Immune	rs28935477, rs1131691986

Unknown
Disease name	Disease term	dbSNP ID	References
Absent eyebrow	Absent eyebrow
Alopecia	Alopecia
Congenital erythropoietic porphyria	Congenital erythropoietic porphyria, Porphyria, Erythropoietic		1733834, 21343304, 9188670, 12060141, 7860775, 2331520, 12533808, 15304101, 22350154, 9803266, 27604308, 1737856, 9834209, 8655129, 21365124, 21653323, 11689424, 11121156
Conjunctivitis	Conjunctivitis
Deficiency of uroporphyrinogen iii synthase	Deficiency of Uroporphyrinogen III Synthase
Dwarfism	Dwarfism
Ectropion	Ectropion
Erosion of cornea	Recurrent erosion of cornea
Hypertrichosis	Hypertrichosis
Hypopigmentation disorder	Hypopigmentation disorder
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes
Keratoconjunctivitis	Keratoconjunctivitis
Osteopenia	Osteopenia
Scleroderma	Scleroderma, Systemic Scleroderma