Neurocirculatory asthenia

Summary

Neurocirculatory asthenia (MONDO:0001315) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neurocirculatory asthenia
Mondo ID	MONDO:0001315
MeSH	D009449
DOID	DOID:11569
SNOMED CT	191962000
UMLS	C1535893
MedGen	283928
Is cancer (heuristic)	no

Also known as: cardiovascular malfunction arising from mental factors

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › somatoform disorder › neurocirculatory asthenia

Related subtypes (5): body dysmorphic disorder, hypochondriasis, somatization disorder, conversion disorder, physiological malfunction arising from mental factor

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

5 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14006	NM_001172501.3(SLC6A2):c.1369G>C (p.Ala457Pro)	SLC6A2	Pathogenic	no assertion criteria provided
3892494	NM_001172501.3(SLC6A2):c.*2901C>T	SLC6A2	Uncertain significance	criteria provided, single submitter
3892495	NM_001172501.3(SLC6A2):c.669G>C (p.Glu223Asp)	SLC6A2	Uncertain significance	criteria provided, single submitter
3892496	NM_001172501.3(SLC6A2):c.407-10C>T	SLC6A2	Uncertain significance	criteria provided, single submitter
3957543	NM_001172501.3(SLC6A2):c.817G>A (p.Val273Met)	SLC6A2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC6A2	Orphanet:443236	Postural orthostatic tachycardia syndrome due to NET 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
SLC6A2	HGNC:11048	ENSG00000103546	P23975	Sodium-dependent noradrenaline transporter	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC6A2	Sodium-dependent noradrenaline transporter	Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC6A2	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_noradrenaline, SNS_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
buccal mucosa cell	1
decidua	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC6A2	121	ubiquitous	marker	placenta, buccal mucosa cell, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC6A2	1,213

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC6A2	P23975	36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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 SLC6A2 causes orthostatic intolerance (OI)	1	2855.0×	0.003	SLC6A2
SLC-mediated transport of neurotransmitters	1	407.9×	0.010	SLC6A2
SLC transporter disorders	1	203.9×	0.011	SLC6A2
R-HSA-425366	1	181.3×	0.011	SLC6A2
Disorders of transmembrane transporters	1	139.3×	0.011	SLC6A2
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC6A2
Transport of small molecules	1	25.1×	0.045	SLC6A2
Disease	1	13.1×	0.076	SLC6A2

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
obsolete norepinephrine transport	1	1872.4×	0.002	SLC6A2
dopamine uptake involved in synaptic transmission	1	1872.4×	0.002	SLC6A2
norepinephrine uptake	1	1872.4×	0.002	SLC6A2
obsolete monoamine transport	1	1203.7×	0.002	SLC6A2
response to pain	1	887.0×	0.002	SLC6A2
neuron cellular homeostasis	1	455.5×	0.004	SLC6A2
neurotransmitter transport	1	421.3×	0.004	SLC6A2
amino acid transport	1	312.1×	0.004	SLC6A2
sodium ion transmembrane transport	1	203.0×	0.006	SLC6A2
chemical synaptic transmission	1	77.3×	0.014	SLC6A2
response to xenobiotic stimulus	1	69.1×	0.014	SLC6A2

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
SLC6A2	CETIRIZINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A2	471	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETIRIZINE	4	SLC6A2
BEPRIDIL	4	SLC6A2
CANDESARTAN CILEXETIL	4	SLC6A2
BEXAROTENE	4	SLC6A2
CLOTRIMAZOLE	4	SLC6A2
AMINOCAPROIC ACID	4	SLC6A2
SIMVASTATIN	4	SLC6A2
NABUMETONE	4	SLC6A2
METAXALONE	4	SLC6A2
ACETOPHENAZINE	4	SLC6A2
MESORIDAZINE	4	SLC6A2
PHENELZINE	4	SLC6A2
NIRAPARIB	4	SLC6A2
INDACATEROL	4	SLC6A2
IMIPRAMINE	4	SLC6A2
EPINASTINE	4	SLC6A2
RIMONABANT	4	SLC6A2
ARIPIPRAZOLE	4	SLC6A2
AMOXAPINE	4	SLC6A2
IDARUBICIN	4	SLC6A2
DESVENLAFAXINE	4	SLC6A2
EZETIMIBE	4	SLC6A2
PONATINIB	4	SLC6A2
DESLORATADINE	4	SLC6A2
RUCAPARIB	4	SLC6A2
DULOXETINE	4	SLC6A2
CELECOXIB	4	SLC6A2
UMECLIDINIUM	4	SLC6A2
TRIMETREXATE	4	SLC6A2
PHENIRAMINE	4	SLC6A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC6A2	929	Binding:885, ADMET:25, Functional:15, Toxicity:3, Unclassified:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SLC6A2	929

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)
CETIRIZINE	4	SLC6A2
BEPRIDIL	4	SLC6A2
CANDESARTAN CILEXETIL	4	SLC6A2
BEXAROTENE	4	SLC6A2
CLOTRIMAZOLE	4	SLC6A2
AMINOCAPROIC ACID	4	SLC6A2
SIMVASTATIN	4	SLC6A2
NABUMETONE	4	SLC6A2
METAXALONE	4	SLC6A2
ACETOPHENAZINE	4	SLC6A2
MESORIDAZINE	4	SLC6A2
PHENELZINE	4	SLC6A2
NIRAPARIB	4	SLC6A2
INDACATEROL	4	SLC6A2
IMIPRAMINE	4	SLC6A2
EPINASTINE	4	SLC6A2
RIMONABANT	4	SLC6A2
ARIPIPRAZOLE	4	SLC6A2
AMOXAPINE	4	SLC6A2
IDARUBICIN	4	SLC6A2
DESVENLAFAXINE	4	SLC6A2
EZETIMIBE	4	SLC6A2
PONATINIB	4	SLC6A2
DESLORATADINE	4	SLC6A2
RUCAPARIB	4	SLC6A2
DULOXETINE	4	SLC6A2
CELECOXIB	4	SLC6A2
UMECLIDINIUM	4	SLC6A2
TRIMETREXATE	4	SLC6A2
PHENIRAMINE	4	SLC6A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC6A2
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.