Brunner syndrome

Summary

Brunner syndrome (MONDO:0010379) is a disease caused by MAOA (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: MAOA (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 150
• Phenotypes (HPO): 2

Clinical features

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0000708	Atypical behavior	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Brunner syndrome
Mondo ID	MONDO:0010379
MeSH	C563156
OMIM	300615
Orphanet	3057
DOID	DOID:0060693
SNOMED CT	718210003
UMLS	C0796275
MedGen	208683
GARD	0003531
Is cancer (heuristic)	no

Also known as: antisocial behavior, X-linked recessive · BRNRS · Brunner syndrome · Brunner syndrome, X-linked recessive · monoamine oxidase A deficiency

Data availability: 150 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › Brunner syndrome

Related subtypes (32): disorder of methionine catabolism, inborn serine deficiency, cerebral creatine deficiency syndrome, inborn organic aciduria, gamma-amino butyric acid metabolism disorder, homocystinuria, urea cycle disorder, adenylosuccinate lyase deficiency, systemic primary carnitine deficiency disease, cystathioninuria, hyperlysinemia, glycine encephalopathy, aminoacylase 1 deficiency, adenine phosphoribosyltransferase deficiency, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, inborn disorder of tryptophan metabolism, inborn disorder of proline metabolism, inborn disorder of ornithine metabolism, inborn disorder of amino acid transport, inborn disorder of histidine metabolism, inborn disorder of phenylalanine and tyrosine metabolism, inborn disorder of branched-chain amino acid metabolism, arakawa syndrome 2, 2-methylacetoacetyl CoA thiolase deficiency, albinism, hyperphenylalaninemia due to DNAJC12 deficiency, inborn disorder of the metabolism of sulfur-containing amino acids and hydrogen sulfide, inborn disorder of glycine and serine metabolism, inborn disorder of ornithine, proline and hydroxyproline metabolism, inborn disorder of glutamate/glutamine and aspartate/asparagine metabolism, hyperglycinemia, transient neonatal, tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

150 retrieved; paginated sample, class counts are floors:

58 likely benign, 56 uncertain significance, 11 benign, 10 conflicting classifications of pathogenicity, 7 pathogenic, 7 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071006	NC_000023.10:g.(?43515570)(43603780_?)del	MAOA	Pathogenic	criteria provided, single submitter
1074868	NM_000240.4(MAOA):c.1214del (p.Gly405fs)	MAOA	Pathogenic	criteria provided, single submitter
139432	NM_000240.4(MAOA):c.797G>T (p.Cys266Phe)	MAOA	Pathogenic	no assertion criteria provided
208352	NM_000240.4(MAOA):c.749_750insT (p.Ser251fs)	MAOA	Pathogenic	criteria provided, single submitter
208353	NM_000240.4(MAOA):c.133C>T (p.Arg45Trp)	MAOA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2422624	NC_000023.10:g.(?43515590)(43817891_?)del	MAOA	Pathogenic	criteria provided, single submitter
3237494	NM_000240.4(MAOA):c.290_303del (p.Leu97fs)	MAOA	Pathogenic	criteria provided, single submitter
9967	NM_000240.4(MAOA):c.886C>T (p.Gln296Ter)	MAOA	Pathogenic	no assertion criteria provided
3256735	NM_000240.4(MAOA):c.1180G>C (p.Glu394Gln)	MAOA	Likely pathogenic	no assertion criteria provided
3600474	NM_000240.4(MAOA):c.11_12del (p.Gln4fs)	MAOA	Likely pathogenic	criteria provided, single submitter
3659338	NM_000240.4(MAOA):c.73+1G>C	MAOA	Likely pathogenic	criteria provided, single submitter
4082335	NM_000240.4(MAOA):c.1420C>T (p.Gln474Ter)	MAOA	Likely pathogenic	criteria provided, single submitter
431096	NM_000240.4(MAOA):c.730G>A (p.Val244Ile)	MAOA	Likely pathogenic	criteria provided, single submitter
4820104	NM_000240.4(MAOA):c.1075del (p.Asp359fs)	MAOA	Likely pathogenic	criteria provided, single submitter
992787	NM_000240.4(MAOA):c.233dup (p.Leu78fs)	MAOA	Likely pathogenic	criteria provided, single submitter
1438897	NM_000240.4(MAOA):c.482T>C (p.Ile161Thr)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1496962	NM_000240.4(MAOA):c.812A>G (p.Asn271Ser)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1691072	NM_000240.4(MAOA):c.933G>T (p.Lys311Asn)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198701	NM_000240.4(MAOA):c.825G>A (p.Pro275=)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2337203	NM_000240.4(MAOA):c.565G>T (p.Val189Leu)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2407239	NM_000240.4(MAOA):c.635A>G (p.Asn212Ser)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282807	NM_000240.4(MAOA):c.1248G>A (p.Met416Ile)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4051013	NM_000240.4(MAOA):c.298T>C (p.Tyr100His)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435816	NM_000240.4(MAOA):c.1559A>G (p.Lys520Arg)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
975746	NM_000240.4(MAOA):c.739G>A (p.Val247Ile)	MAOA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034122	NM_000240.4(MAOA):c.411+12G>A	MAOA	Uncertain significance	criteria provided, single submitter
1035352	NM_000240.4(MAOA):c.1440C>A (p.Asp480Glu)	MAOA	Uncertain significance	criteria provided, single submitter
1064570	NM_000240.4(MAOA):c.805G>A (p.Val269Ile)	MAOA	Uncertain significance	criteria provided, multiple submitters, no conflicts
1307018	NM_000240.4(MAOA):c.172G>A (p.Glu58Lys)	MAOA	Uncertain significance	criteria provided, multiple submitters, no conflicts
1333950	NM_000240.4(MAOA):c.374A>G (p.Asn125Ser)	MAOA	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MAOA	Definitive	X-linked	Brunner syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAOA	Orphanet:3057	Monoamine oxidase A deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MAOA	HGNC:6833	ENSG00000189221	P21397	Amine oxidase [flavin-containing] A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAOA	Amine oxidase [flavin-containing] A	Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAOA	Enzyme (other)	yes	1.4.3.4	Flavin_amine_oxidase, Amino_oxidase, FAD/NAD-bd_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic mucosa	1
ileal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAOA	285	ubiquitous	marker	ileal mucosa, colonic mucosa, mucosa of sigmoid colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAOA	3,282

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAOA	P21397	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective MAOA causes BRUNS	1	11420.0×	7e-04	MAOA
Amine Oxidase reactions	1	5710.0×	7e-04	MAOA
Biogenic amines are oxidatively deaminated to aldehydes by MAOA and MAOB	1	5710.0×	7e-04	MAOA
Enzymatic degradation of Dopamine by monoamine oxidase	1	5710.0×	7e-04	MAOA
Dopamine clearance from the synaptic cleft	1	5710.0×	7e-04	MAOA
Metabolism of serotonin	1	5710.0×	7e-04	MAOA
Enzymatic degradation of dopamine by COMT	1	3806.7×	9e-04	MAOA
Serotonin clearance from the synaptic cleft	1	2855.0×	0.001	MAOA
Neurotransmitter clearance	1	1268.9×	0.002	MAOA
Metabolic disorders of biological oxidation enzymes	1	878.5×	0.003	MAOA
Norepinephrine Neurotransmitter Release Cycle	1	634.4×	0.003	MAOA
Neurotransmitter release cycle	1	439.2×	0.004	MAOA
Phase I - Functionalization of compounds	1	219.6×	0.008	MAOA
Biological oxidations	1	129.8×	0.013	MAOA
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.015	MAOA
Diseases of metabolism	1	80.4×	0.018	MAOA
Transmission across Chemical Synapses	1	76.1×	0.018	MAOA
Signaling by Interleukins	1	64.2×	0.020	MAOA
Neuronal System	1	44.3×	0.027	MAOA
Cytokine Signaling in Immune system	1	40.8×	0.028	MAOA
Disease	1	13.1×	0.081	MAOA
Immune System	1	13.0×	0.081	MAOA
Metabolism	1	11.6×	0.086	MAOA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
serotonin catabolic process	1	8426.0×	4e-04	MAOA
biogenic amine metabolic process	1	5617.3×	4e-04	MAOA
dopamine catabolic process	1	1685.2×	8e-04	MAOA
positive regulation of signal transduction	1	1296.3×	8e-04	MAOA

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MAOA	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAOA	130	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	MAOA
NABUMETONE	4	MAOA
METAXALONE	4	MAOA
PHENELZINE	4	MAOA
ARIPIPRAZOLE	4	MAOA
PONATINIB	4	MAOA
CHLOROPROCAINE	4	MAOA
TRIMETREXATE	4	MAOA
PROPARACAINE	4	MAOA
ETHYNODIOL DIACETATE	4	MAOA
SELEGILINE HYDROCHLORIDE	4	MAOA
RASAGILINE MESYLATE	4	MAOA
PYRVINIUM	4	MAOA
ETHOPROPAZINE	4	MAOA
ROSIGLITAZONE	4	MAOA
TEDIZOLID	4	MAOA
LINEZOLID	4	MAOA
SERTINDOLE	4	MAOA
SORAFENIB	4	MAOA
NITAZOXANIDE	4	MAOA
NICLOSAMIDE	4	MAOA
TRIOXSALEN	4	MAOA
VARDENAFIL	4	MAOA
PYRANTEL	4	MAOA
DEBRISOQUIN	4	MAOA
TOLOXATONE	4	MAOA
PHENOXYPROPAZINE	4	MAOA
METHYLENE BLUE CATION	4	MAOA
NIFEDIPINE	4	MAOA
REGORAFENIB	4	MAOA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MAOA	1,269	Binding:1213, ADMET:36, Toxicity:14, Functional:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MAOA	1.4.3.4	monoamine oxidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MAOA	1,269

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CLOTRIMAZOLE	4	MAOA
NABUMETONE	4	MAOA
METAXALONE	4	MAOA
PHENELZINE	4	MAOA
ARIPIPRAZOLE	4	MAOA
PONATINIB	4	MAOA
CHLOROPROCAINE	4	MAOA
TRIMETREXATE	4	MAOA
PROPARACAINE	4	MAOA
ETHYNODIOL DIACETATE	4	MAOA
SELEGILINE HYDROCHLORIDE	4	MAOA
RASAGILINE MESYLATE	4	MAOA
PYRVINIUM	4	MAOA
ETHOPROPAZINE	4	MAOA
ROSIGLITAZONE	4	MAOA
TEDIZOLID	4	MAOA
LINEZOLID	4	MAOA
SERTINDOLE	4	MAOA
SORAFENIB	4	MAOA
NITAZOXANIDE	4	MAOA
NICLOSAMIDE	4	MAOA
TRIOXSALEN	4	MAOA
VARDENAFIL	4	MAOA
PYRANTEL	4	MAOA
DEBRISOQUIN	4	MAOA
TOLOXATONE	4	MAOA
PHENOXYPROPAZINE	4	MAOA
METHYLENE BLUE CATION	4	MAOA
NIFEDIPINE	4	MAOA
REGORAFENIB	4	MAOA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MAOA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.