Protein / target

Succinate-semialdehyde dehydrogenase, mitochondrial

ALDH5A1P51649Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Succinate-semialdehyde dehydrogenase (NAD+) activity

Primary system

Nervous system

Strongest disease association

succinic semialdehyde dehydrogenase deficiency

Genetic evidence · score 0.92

Therapeutic maturity

Clinically validated target

3 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

3 approved

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)

Subcellular location

Mitochondrion
Domains and Gene Ontology detail (8)

Gene Ontology

  • Cmitochondrial matrix
  • Cmitochondrion
  • Fidentical protein binding
  • Fsuccinate-semialdehyde dehydrogenase (NAD+) activity
  • Pcentral nervous system development
  • Pgamma-aminobutyric acid catabolic process
  • Pglutamate metabolic process
  • Psuccinate metabolic process

535 aa · 57 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·succinate-semialdehyde dehydrogenase (NAD+) activity
  • ·glutamate metabolic process
  • ·succinate metabolic process
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

ABATCSOGDHMDH2ACLYIDH2IDH1PCOGDHLIDH3AALDH5A1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Valproic Acid
Narrow target profileApprovedInhibitor

Succinate semialdehyde dehydrogenase inhibitor

Appears in clinical studies involving Generalized non-motor (absence) seizure, complex partial epilepsy, epilepsy, Seizure

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

succinic semialdehyde dehydrogenase deficiency0.92

Genetic · overall 0.84

hereditary disease0.86

Genetic · overall 0.52

Seizure0.19

Genetic · overall 0.60

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

epilepsy1.00

Clinical · overall 0.61

bipolar disorder0.99

Clinical · overall 0.61

major depressive disorder0.94

Clinical · overall 0.57

migraine disorder0.86

Clinical · overall 0.52

Generalized non-motor (absence) seizure0.76

Clinical · overall 0.47

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

complex partial epilepsy0.46

Clinical

bipolar I disorder0.39

Clinical

Show all associations
succinic semialdehyde dehydrogenase deficiency0.84
epilepsy0.61
bipolar disorder0.61
Seizure0.60
major depressive disorder0.57
hereditary disease0.52
migraine disorder0.52
Generalized non-motor (absence) seizure0.47
complex partial epilepsy0.46
bipolar I disorder0.39

Open Targets ranks 1,172 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 3 total

VALPROIC ACIDApproval

Generalized non-motor (absence) seizure · complex partial epilepsy · epilepsy

DIVALPROEX SODIUMApproval

Generalized non-motor (absence) seizure · bipolar disorder · epilepsy

VALPROATE SODIUMApproval

epilepsy · neuropathic pain · alcohol dependence

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

TERMINATED · via Valproic Acid · NCT00063362

TERMINATED · via Valproic Acid · NCT00312546

COMPLETED · via Valproic Acid · NCT01586208

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

succinic semialdehyde dehydrogenase deficiencyWell supported
0.94
agreement 0.821.00
Genetic83%Animal model13%Literature4%Genetic literaturedup

Open Targets aggregate 0.84 · 3 independent evidence families · 1 not counted as duplicate

hereditary diseaseWell supported
0.86
agreement 0.721.00
Genetic98%Literature2%

Open Targets aggregate 0.52 · 2 independent evidence families

SeizureWell supported
0.76
agreement 0.660.86
Clinical78%Genetic22%

Open Targets aggregate 0.60 · 2 independent evidence families

epilepsyWell supported
0.75
agreement 0.600.91
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

bipolar disorderModerately supported
0.75
agreement 0.590.90
Clinical99%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

13

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. Supplemental approval2026-06-25

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  2. New publication2020-04-14
    A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high-grade glioma.

    Pediatric blood & cancer · 2020 · 50 citations · Europe PMC · via Valproic Acid

  3. New publication2018-03-14
    Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

    Bipolar disorders · 2018 · 1,126 citations · Europe PMC · via Valproic Acid

  4. Label change2015-12-26

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  5. Label change2015-12-26

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  6. Label change2014-08-05

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  7. Supplemental approval2001-06-29

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  8. Label change2001-01-18

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  9. Supplemental approval2000-01-27

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  10. Supplemental approval1998-10-14

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  11. Supplemental approval1996-11-15

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  12. Supplemental approval1993-01-15

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.