Hereditary sensory and autonomic neuropathy type 7
diseaseOn this page
Also known as autosomal dominant hereditary sensory and autonomic neuropathy caused by mutation in SCN11ACIP with hyperhidrosis and gastrointestinal dysfunctioncongenital insensitivity to pain with hyperhidrosis and gastrointestinal dysfunctionhereditary sensory and autonomic neuropathy type VIIhereditary sensory and autonomic neuropathy with hyperhidrosis and gastrointestinal dysfunctionHSAN VIIHSAN with hyperhidrosis and gastrointestinal dysfunctionHSAN7neuropathy, hereditary sensory and autonomic, type VIISCN11A autosomal dominant hereditary sensory and autonomic neuropathy
Summary
Hereditary sensory and autonomic neuropathy type 7 (MONDO:0014244) is a disease caused by SCN11A (GenCC Definitive), with 2 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: SCN11A (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 1,383
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 3 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hereditary sensory and autonomic neuropathy type 7 |
| Mondo ID | MONDO:0014244 |
| OMIM | 615548 |
| Orphanet | 391397 |
| DOID | DOID:0070149 |
| NCIT | C125388 |
| UMLS | C3809882 |
| MedGen | 816212 |
| GARD | 0012732 |
| Is cancer (heuristic) | no |
Also known as: autosomal dominant hereditary sensory and autonomic neuropathy caused by mutation in SCN11A · CIP with hyperhidrosis and gastrointestinal dysfunction · congenital insensitivity to pain with hyperhidrosis and gastrointestinal dysfunction · hereditary sensory and autonomic neuropathy type VII · hereditary sensory and autonomic neuropathy with hyperhidrosis and gastrointestinal dysfunction · HSAN VII · HSAN with hyperhidrosis and gastrointestinal dysfunction · HSAN7 · neuropathy, hereditary sensory and autonomic, type VII · SCN11A autosomal dominant hereditary sensory and autonomic neuropathy
Data availability: 1,383 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › sensory peripheral neuropathy › hereditary sensory and autonomic neuropathy › hereditary sensory and autonomic neuropathy type 7
Related subtypes (12): polyneuropathy-hand defect syndrome, hereditary sensory and autonomic neuropathy type 4, neuropathy, hereditary sensory, atypical, X-linked hereditary sensory and autonomic neuropathy with hearing loss, hereditary sensory neuropathy X-linked, hereditary sensory and autonomic neuropathy type 5, hereditary sensory and autonomic neuropathy type 6, congenital insensitivity to pain-hypohidrosis syndrome, congenital insensitivity to pain with hyperhidrosis, hereditary sensory and autonomic neuropathy type 1, cold-induced sweating syndrome - hyperthermia spectrum, hereditary sensory and autonomic neuropathy type 2
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
600 retrieved; paginated sample, class counts are floors:
347 uncertain significance, 206 likely benign, 24 conflicting classifications of pathogenicity, 18 benign, 5 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1001012 | NM_001349253.2(SCN11A):c.4414C>T (p.Arg1472Ter) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1002213 | NM_001349253.2(SCN11A):c.3010G>A (p.Gly1004Arg) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1014224 | NM_001349253.2(SCN11A):c.4978G>A (p.Ala1660Thr) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1017449 | NM_001349253.2(SCN11A):c.3467G>A (p.Arg1156His) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1039827 | NM_001349253.2(SCN11A):c.4640T>C (p.Ile1547Thr) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1056448 | NM_001349253.2(SCN11A):c.89G>A (p.Arg30Gln) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1060572 | NM_001349253.2(SCN11A):c.1913G>A (p.Arg638His) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1142743 | NM_001349253.2(SCN11A):c.4057-6del | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1352340 | NM_001349253.2(SCN11A):c.2222C>T (p.Pro741Leu) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1397095 | NM_001349253.2(SCN11A):c.923C>T (p.Pro308Leu) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1463207 | NM_001349253.2(SCN11A):c.2404-6T>C | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1476674 | NM_001349253.2(SCN11A):c.4081G>A (p.Asp1361Asn) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1516982 | NM_001349253.2(SCN11A):c.2518C>T (p.Arg840Cys) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1542161 | NM_001349253.2(SCN11A):c.970A>G (p.Ile324Val) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 157599 | NM_001349253.2(SCN11A):c.3473T>C (p.Leu1158Pro) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 157600 | NM_001349253.2(SCN11A):c.1142T>C (p.Ile381Thr) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1675178 | NM_001349253.2(SCN11A):c.3366G>A (p.Trp1122Ter) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1685430 | NM_001349253.2(SCN11A):c.712+1G>A | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1737551 | NM_001349253.2(SCN11A):c.4070G>C (p.Gly1357Ala) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1798487 | NM_001349253.2(SCN11A):c.298A>G (p.Ile100Val) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1805943 | NM_001349253.2(SCN11A):c.4894A>G (p.Lys1632Glu) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1928733 | NM_001349253.2(SCN11A):c.4322T>C (p.Ile1441Thr) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2379025 | NM_001349253.2(SCN11A):c.1912C>T (p.Arg638Cys) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2922596 | NM_001349253.2(SCN11A):c.2479G>T (p.Ala827Ser) | SCN11A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1055871 | NM_001349253.2(SCN11A):c.3693C>A (p.Phe1231Leu) | LOC126806652 | Uncertain significance | criteria provided, single submitter |
| 1374373 | NM_001349253.2(SCN11A):c.3509C>T (p.Ala1170Val) | LOC126806652 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1489622 | NM_001349253.2(SCN11A):c.3655A>G (p.Ile1219Val) | LOC126806652 | Uncertain significance | criteria provided, single submitter |
| 1503941 | NM_001349253.2(SCN11A):c.3746C>T (p.Ala1249Val) | LOC126806652 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1517780 | NM_001349253.2(SCN11A):c.3578G>T (p.Cys1193Phe) | LOC126806652 | Uncertain significance | criteria provided, single submitter |
| 1715954 | NM_001349253.2(SCN11A):c.3745G>C (p.Ala1249Pro) | LOC126806652 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 8 · Orphanet: 12 · 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 |
|---|---|---|---|---|
| SCN11A | Definitive | Autosomal dominant | hereditary sensory and autonomic neuropathy type 7 | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SCN11A | Orphanet:306577 | Hereditary sodium channelopathy-related small fibers neuropathy |
| SCN11A | Orphanet:391392 | Familial episodic pain syndrome with predominantly lower limb involvement |
| SCN11A | Orphanet:391397 | Hereditary sensory and autonomic neuropathy type 7 |
| SCN11A | Orphanet:46348 | Paroxysmal extreme pain disorder |
| SCN11A | Orphanet:88642 | Congenital insensitivity to pain-anosmia-neuropathic arthropathy |
| SCN11A | Orphanet:90026 | Primary erythromelalgia |
| SCN10A | Orphanet:101016 | Romano-Ward syndrome |
| SCN10A | Orphanet:130 | Brugada syndrome |
| SCN10A | Orphanet:306577 | Hereditary sodium channelopathy-related small fibers neuropathy |
| SCN10A | Orphanet:46348 | Paroxysmal extreme pain disorder |
| SCN10A | Orphanet:88642 | Congenital insensitivity to pain-anosmia-neuropathic arthropathy |
| SCN10A | Orphanet:90026 | Primary erythromelalgia |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SCN11A | HGNC:10583 | ENSG00000168356 | Q9UI33 | Sodium channel protein type 11 subunit alpha | gencc,clinvar |
| SCN10A | HGNC:10582 | ENSG00000185313 | Q9Y5Y9 | Sodium channel protein type 10 subunit alpha | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SCN11A | Sodium channel protein type 11 subunit alpha | Sodium channel mediating the voltage-dependent sodium ion permeability of excitable membranes. |
| SCN10A | Sodium channel protein type 10 subunit alpha | Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. |
Protein-family classification
Druggable: 2 · 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 |
|---|---|---|---|
| Ion channel | 2 | 111.5× | 8e-05 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SCN11A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom | |
| SCN10A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| buccal mucosa cell | 1 |
| dorsal root ganglion | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| diaphragm | 1 |
| olfactory bulb | 1 |
| type B pancreatic cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SCN11A | 166 | broad | marker | buccal mucosa cell, dorsal root ganglion, male germ line stem cell (sensu Vertebrata) in testis |
| SCN10A | 21 | marker | type B pancreatic cell, olfactory bulb, diaphragm |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SCN10A | 1,802 |
| SCN11A | 1,202 |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SCN10A | Q9Y5Y9 | 8 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SCN11A | Q9UI33 | 69.66 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Interaction between L1 and Ankyrins | 2 | 368.4× | 3e-05 | SCN11A, SCN10A |
| Phase 0 - rapid depolarisation | 2 | 346.1× | 3e-05 | SCN11A, SCN10A |
| L1CAM interactions | 2 | 120.2× | 2e-04 | SCN11A, SCN10A |
| Cardiac conduction | 2 | 108.8× | 2e-04 | SCN11A, SCN10A |
| Muscle contraction | 2 | 77.2× | 3e-04 | SCN11A, SCN10A |
| Axon guidance | 2 | 45.1× | 6e-04 | SCN11A, SCN10A |
| Nervous system development | 2 | 42.9× | 6e-04 | SCN11A, SCN10A |
| Developmental Biology | 2 | 14.5× | 0.005 | SCN11A, SCN10A |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| membrane depolarization during action potential | 2 | 1685.2× | 1e-05 | SCN11A, SCN10A |
| cardiac muscle cell action potential involved in contraction | 2 | 702.2× | 4e-05 | SCN11A, SCN10A |
| sodium ion transmembrane transport | 2 | 203.0× | 3e-04 | SCN11A, SCN10A |
| reflex | 1 | 8426.0× | 0.001 | SCN11A |
| small intestine smooth muscle contraction | 1 | 8426.0× | 0.001 | SCN11A |
| thermosensory behavior | 1 | 4213.0× | 0.001 | SCN11A |
| behavioral response to acetic acid induced pain | 1 | 4213.0× | 0.001 | SCN11A |
| bundle of His cell action potential | 1 | 4213.0× | 0.001 | SCN10A |
| response to high light intensity | 1 | 2808.7× | 0.001 | SCN11A |
| micturition | 1 | 2808.7× | 0.001 | SCN11A |
| behavioral response to formalin induced pain | 1 | 2808.7× | 0.001 | SCN11A |
| action potential initiation | 1 | 2808.7× | 0.001 | SCN11A |
| thigmotaxis | 1 | 2106.5× | 0.001 | SCN11A |
| AV node cell action potential | 1 | 2106.5× | 0.001 | SCN10A |
| response to nitric oxide | 1 | 1685.2× | 0.002 | SCN11A |
| calcitonin gene-related peptide receptor signaling pathway | 1 | 1404.3× | 0.002 | SCN11A |
| skeletal muscle organ development | 1 | 1053.2× | 0.002 | SCN11A |
| regulation of atrial cardiac muscle cell membrane depolarization | 1 | 936.2× | 0.002 | SCN10A |
| sensory perception of itch | 1 | 936.2× | 0.002 | SCN11A |
| acute inflammatory response | 1 | 842.6× | 0.002 | SCN11A |
| chronic inflammatory response | 1 | 842.6× | 0.002 | SCN11A |
| sensory perception | 1 | 702.2× | 0.002 | SCN10A |
| response to prostaglandin E | 1 | 702.2× | 0.002 | SCN11A |
| artery development | 1 | 702.2× | 0.002 | SCN11A |
| cAMP/PKA signal transduction | 1 | 702.2× | 0.002 | SCN11A |
| detection of mechanical stimulus involved in sensory perception of pain | 1 | 561.7× | 0.003 | SCN11A |
| cellular response to cold | 1 | 526.6× | 0.003 | SCN11A |
| regulation of cardiac muscle contraction | 1 | 443.5× | 0.003 | SCN10A |
| detection of temperature stimulus involved in sensory perception of pain | 1 | 421.3× | 0.004 | SCN11A |
| response to auditory stimulus | 1 | 366.4× | 0.004 | SCN11A |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0
Druggability breadth: 2 of 2 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 |
|---|---|
| SCN11A | IMIPRAMINE |
| SCN10A | IMIPRAMINE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SCN10A | 21 | 4 |
| SCN11A | 15 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| IMIPRAMINE | 4 | SCN10A, SCN11A |
| SERTINDOLE | 4 | SCN10A, SCN11A |
| PIMOZIDE | 4 | SCN10A, SCN11A |
| NIFEDIPINE | 4 | SCN10A, SCN11A |
| DILTIAZEM | 4 | SCN10A, SCN11A |
| MIBEFRADIL | 4 | SCN10A, SCN11A |
| HALOPERIDOL | 4 | SCN10A, SCN11A |
| MEXILETINE | 4 | SCN10A, SCN11A |
| AMITRIPTYLINE | 4 | SCN10A, SCN11A |
| AMIODARONE | 4 | SCN10A, SCN11A |
| CHLORPROMAZINE | 4 | SCN10A, SCN11A |
| LAMOTRIGINE | 4 | SCN10A |
| TEDISAMIL | 3 | SCN10A, SCN11A |
| NITRENDIPINE | 3 | SCN10A, SCN11A |
| AJMALINE | 3 | SCN10A, SCN11A |
| VIXOTRIGINE | 3 | SCN10A |
| ELECLAZINE | 3 | SCN10A |
| CIFENLINE | 2 | SCN10A, SCN11A |
| PF-04531083 | 2 | SCN10A |
| FUNAPIDE | 2 | SCN10A |
| PF-06305591 | 1 | SCN10A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SCN10A | 144 | Binding:124, Functional:16, ADMET:4 |
| SCN11A | 33 | Functional:16, Binding:15, ADMET:2 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SCN10A | 144 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
21 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) |
|---|---|---|
| IMIPRAMINE | 4 | SCN10A, SCN11A |
| SERTINDOLE | 4 | SCN10A, SCN11A |
| PIMOZIDE | 4 | SCN10A, SCN11A |
| NIFEDIPINE | 4 | SCN10A, SCN11A |
| DILTIAZEM | 4 | SCN10A, SCN11A |
| MIBEFRADIL | 4 | SCN10A, SCN11A |
| HALOPERIDOL | 4 | SCN10A, SCN11A |
| MEXILETINE | 4 | SCN10A, SCN11A |
| AMITRIPTYLINE | 4 | SCN10A, SCN11A |
| AMIODARONE | 4 | SCN10A, SCN11A |
| CHLORPROMAZINE | 4 | SCN10A, SCN11A |
| LAMOTRIGINE | 4 | SCN10A |
| TEDISAMIL | 3 | SCN10A, SCN11A |
| NITRENDIPINE | 3 | SCN10A, SCN11A |
| AJMALINE | 3 | SCN10A, SCN11A |
| VIXOTRIGINE | 3 | SCN10A |
| ELECLAZINE | 3 | SCN10A |
| CIFENLINE | 2 | SCN10A, SCN11A |
| PF-04531083 | 2 | SCN10A |
| FUNAPIDE | 2 | SCN10A |
| PF-06305591 | 1 | SCN10A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | SCN11A, SCN10A |
| 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.