SPR

sepiapterin reductase

2 disorders 2 causative 2p13.2 gene with protein product

HGNC:11257 Monarch NCBI Gene 6697 ENSG00000116096 UniProt P35270 OMIM 182125

Aliases: SDR38C1.

Normal function · from ai-gene-review (P35270, commit 79fe13b38970) · AI-generated, not KB evidence

Sepiapterin reductase (SPR) is a short-chain dehydrogenase/reductase (SDR) family enzyme that catalyzes the terminal reduction steps in the de novo and salvage biosynthesis of tetrahydrobiopterin (BH4). In the de novo pathway, SPR reduces 6-pyruvoyl-tetrahydropterin through 1'-oxo and 2'-oxo intermediates to BH4. In the salvage pathway, it reduces sepiapterin to 7,8-dihydrobiopterin (BH2). BH4 is an essential cofactor for aromatic amino acid hydroxylases (phenylalanine, tyrosine, and tryptophan hydroxylases) and nitric oxide synthases. SPR deficiency causes DOPA-responsive dystonia with monoamine neurotransmitter deficiency without hyperphenylalaninemia. The enzyme is a cytosolic homodimer that uses NADPH as cofactor.

Core enzymatic function. SPR catalyzes the NADPH-dependent reduction of sepiapterin and 6-pyruvoyl-tetrahydropterin intermediates to form tetrahydrobiopterin. EC 1.1.1.153. Kinetic parameters: Km 14.3 uM sepiapterin, Km 10 uM NADPH, kcat 1.1 s-1. Crystal structure solved (PDB:6I6V at 1.43 A). Homodimer.

molecular function: sepiapterin reductase (NADP+) activity

NADP cofactor binding function. SPR binds NADPH as the reducing cofactor. Multiple NADP binding sites identified by X-ray crystallography (PDB:1Z6Z, 6I6V). Km for NADPH is 10 uM. Member of short-chain dehydrogenase/reductase (SDR) superfamily.

molecular function: NADP binding

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Disorder of Catecholamine Synthesis	causative germline	mechanism: BH4 Cofactor Deficiency subtype: Sepiapterin reductase deficiency scoped to subtype: Sepiapterin reductase deficiency
Tetrahydrobiopterin Deficiency	causative	mechanism: BH4 Biosynthesis and Regeneration Gene Defect subtype: SPR Deficiency scoped to subtype: SPR Deficiency

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994	AR	Definitive 2021-06-04	Disorder of Catecholamine Synthesis causative Tetrahydrobiopterin Deficiency causative

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.