Sensory peripheral neuropathy

Summary

Sensory peripheral neuropathy (MONDO:0002321) is a disease with 8 cohort genes (22 GWAS associations across 3 studies) and 5 clinical trials. Top therapeutic interventions include acetylcarnitine.

At a glance

• Cohort genes: 8
• GWAS associations: 22
• ClinVar variants: 7
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sensory peripheral neuropathy
Mondo ID	MONDO:0002321
DOID	DOID:2491
NCIT	C3501
SNOMED CT	95662005
UMLS	C0151313
MedGen	101791
Anatomy (UBERON)	UBERON:0001027
Is cancer (heuristic)	no

Also known as: peripheral neuropathy of sensory nerve · peripheral sensory neuropathy · sensory nerve peripheral neuropathy

Data availability: 7 ClinVar variants · 22 GWAS associations (3 studies) · 1 GenCC gene-disease record · 1 cell line.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › sensory peripheral neuropathy

Related subtypes (29): autoimmune neuropathy, autonomic neuropathy, mononeuropathy, ischemic neuropathy, polyneuropathy, neuritis, motor peripheral neuropathy, uremic neuropathy, nerve compression syndrome, axonal neuropathy, diabetic neuropathy, acquired peripheral neuropathy, hereditary peripheral neuropathy, neuralgia, peripheral nerve lesion, nerve plexus disorder, traumatic neuropathy, radiation-induced neuropathy, vasculitic neuropathy, chronic idiopathic neuropathy, chemotherapy-induced neuropathy, infectious neuropathy, vitamin deficiency related neuropathy, paraproteinemia-associated neuropathy, neuropathy in cryoglobulinemia, neuropathy in endocrine disorder, sarcoid neuropathy, neuropathy, small fiber, idiopathic small fibers neuropathy

Subtypes (1): hereditary sensory and autonomic neuropathy

Genetics & variants

GWAS landscape

22 GWAS associations across 3 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs17018026	3e-07	DCDC2C	A	1.31
rs146474026	3e-07	CACNB4	T	2.03
rs35925426	5e-07	GNG5P1 - PRR18	A	0.75
rs7338725	5e-07	NUS1P2 - HMGA1P6	G	1.33
rs17610383	2e-06	LINC00907	A	2.3
rs141164127	2e-06	GAS7	C	2.12
rs6829206	3e-06	GABRB1	T	2.14
rs7169642	3e-06	MEX3B - LINC01583	T	0.61
rs11159547	3e-06	Metazoa_SRP - LINC02301	T	1.29
rs12501594	4e-06	NDUFB5P1 - LINC00290	T	3.09
rs112917429	4e-06	RECK	A	2.33
rs555118050	4e-06	CSMD1	C	3.06
rs117036130	5e-06	ATP7B	C	0.2
rs149840913	5e-06	NEFHP2 - PTPRT	T	2.56
rs62447871	5e-06	RBMX2P4 - ETV1	T	1.29
rs494821	5e-06	RUNX1T1 - FLJ46284	G	0.76
rs76299149	6e-06	LSAMP	A	1.72
rs9476901	8e-06	DTNBP1 - ARPC3P5	C	1.57
rs2181623	8e-06	LINC02649	T	4.86
rs1642592	9e-06	MPP2	C	1.61
rs7009093	9e-06	DLC1 - SGCZ	G	2.83
rs62407462	1e-05	LMBRD1	C	1.28

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90060085	Kanai M	2021	383	0	Large-Scale Prospective Genome-Wide Association Study of Oxaliplatin in Stage II/III Colon Cancer and Neuropathy.
GCST90060086	Kanai M	2021	233	0	Large-Scale Prospective Genome-Wide Association Study of Oxaliplatin in Stage II/III Colon Cancer and Neuropathy.
GCST90060087	Kanai M	2021	0	0	Large-Scale Prospective Genome-Wide Association Study of Oxaliplatin in Stage II/III Colon Cancer and Neuropathy.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	22

MAF distribution

Bucket	Variants
common (>=0.05)	14
low_freq (0.01-0.05)	4
rare (<0.01)	4
unknown	0

Functional consequences

Consequence	Count
intron_variant	17
intergenic_variant	5

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs17018026	2	3789170	G>A	0.39	intron_variant	DCDC2C	3e-07	Tier 4: intronic/intergenic
rs146474026	2	152041356	C>T	0.011	intron_variant	CACNB4	3e-07	Tier 4: intronic/intergenic
rs35925426	6	166245457	G>A	0.41	intron_variant	GNG5P1 - PRR18	5e-07	Tier 4: intronic/intergenic
rs7338725	13	22983403	C>G	0.24	intergenic_variant	NUS1P2 - HMGA1P6	5e-07	Tier 4: intronic/intergenic
rs17610383	18	42312316	G>A,T	0.06	intron_variant	LINC00907	2e-06	Tier 4: intronic/intergenic
rs141164127	17	9947313	T>C	0.004	intron_variant	GAS7	2e-06	Tier 4: intronic/intergenic
rs6829206	4	47050589	A>C,T	0.17	intron_variant	GABRB1	3e-06	Tier 4: intronic/intergenic
rs7169642	15	82068472	C>G,T	0.38	intergenic_variant	MEX3B - LINC01583	3e-06	Tier 4: intronic/intergenic
rs11159547	14	82488777	C>T	0.33	intergenic_variant	Metazoa_SRP - LINC02301	3e-06	Tier 4: intronic/intergenic
rs12501594	4	180604995	C>G,T	0.021	intergenic_variant	NDUFB5P1 - LINC00290	4e-06	Tier 4: intronic/intergenic
rs112917429	9	36101020	G>A	0.046	intron_variant	RECK	4e-06	Tier 4: intronic/intergenic
rs555118050	8	3240751	G>A,C,T	0.002	intron_variant	CSMD1	4e-06	Tier 4: intronic/intergenic
rs117036130	13	51977658	T>C	0.25	intron_variant	ATP7B	5e-06	Tier 4: intronic/intergenic
rs149840913	20	42053075	C>G,T	0.002	intron_variant	NEFHP2 - PTPRT	5e-06	Tier 4: intronic/intergenic
rs62447871	7	13234971	A>C,T	0.24	intron_variant	RBMX2P4 - ETV1	5e-06	Tier 4: intronic/intergenic
rs494821	8	92475593	C>A,G,T	0.2	intron_variant	RUNX1T1 - FLJ46284	5e-06	Tier 4: intronic/intergenic
rs76299149	3	117254892	G>A	0.17	intergenic_variant	LSAMP	6e-06	Tier 4: intronic/intergenic
rs9476901	6	15731075	T>A,C,G	0.49	intron_variant	DTNBP1 - ARPC3P5	8e-06	Tier 4: intronic/intergenic
rs2181623	10	6349529	C>A,G,T	0.26	intron_variant	LINC02649	8e-06	Tier 4: intronic/intergenic
rs1642592	17	43891933	A>C,G,T	0.033	intron_variant	MPP2	9e-06	Tier 4: intronic/intergenic
rs7009093	8	13733216	C>G,T	0.002	intron_variant	DLC1 - SGCZ	9e-06	Tier 4: intronic/intergenic
rs62407462	6	69805213	T>A,C	0.42	intron_variant	LMBRD1	1e-05	Tier 4: intronic/intergenic

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 2 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4200	NM_018972.4(GDAP1):c.715C>T (p.Leu239Phe)	GDAP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14176	NM_000530.8(MPZ):c.293G>A (p.Arg98His)	MPZ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
243088	NM_018327.4(SPTLC3):c.448T>C (p.Trp150Arg)	SPTLC3	Likely pathogenic	criteria provided, single submitter
373934	NM_000166.6(GJB1):c.502T>G (p.Cys168Gly)	GJB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679383	NM_014053.4(FLVCR1):c.323T>C (p.Phe108Ser)	FLVCR1	Uncertain significance	criteria provided, single submitter
373970	NM_001077365.2(POMT1):c.1793G>A (p.Arg598Gln)	POMT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
701958	NM_001349253.2(SCN11A):c.4628G>A (p.Cys1543Tyr)	SCN11A	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 28 · 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
SMPDL3A	Limited	Autosomal recessive	sensory peripheral neuropathy

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
GDAP1	Orphanet:101097	Autosomal recessive Charcot-Marie-Tooth disease with hoarseness
GDAP1	Orphanet:101102	Charcot-Marie-Tooth disease type 2H
GDAP1	Orphanet:217055	Autosomal recessive intermediate Charcot-Marie-Tooth disease type A
GDAP1	Orphanet:99944	Autosomal dominant Charcot-Marie-Tooth disease type 2K
GDAP1	Orphanet:99948	Charcot-Marie-Tooth disease type 4A
FLVCR1	Orphanet:88628	Posterior column ataxia-retinitis pigmentosa syndrome
GJB1	Orphanet:101075	X-linked Charcot-Marie-Tooth disease type 1
GJB1	Orphanet:1175	X-linked progressive cerebellar ataxia
MPZ	Orphanet:100046	Autosomal dominant intermediate Charcot-Marie-Tooth disease type D
MPZ	Orphanet:101082	Charcot-Marie-Tooth disease type 1B
MPZ	Orphanet:3115	Roussy-Lévy syndrome
MPZ	Orphanet:324585	Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain
MPZ	Orphanet:538574	Palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome
MPZ	Orphanet:64748	Dejerine-Sottas syndrome
MPZ	Orphanet:99942	Autosomal dominant Charcot-Marie-Tooth disease type 2I
MPZ	Orphanet:99943	Autosomal dominant Charcot-Marie-Tooth disease type 2J
POMT1	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
POMT1	Orphanet:370968	Congenital muscular dystrophy with intellectual disability
POMT1	Orphanet:370980	Congenital muscular dystrophy without intellectual disability
POMT1	Orphanet:588	Muscle-eye-brain disease
POMT1	Orphanet:86812	POMT1-related limb-girdle muscular dystrophy R11
POMT1	Orphanet:899	Walker-Warburg syndrome

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMPDL3A	HGNC:17389	ENSG00000172594	Q92484	Cyclic GMP-AMP phosphodiesterase SMPDL3A	gencc
SCN11A	HGNC:10583	ENSG00000168356	Q9UI33	Sodium channel protein type 11 subunit alpha	clinvar
GDAP1	HGNC:15968	ENSG00000104381	Q8TB36	Ganglioside-induced differentiation-associated protein 1	clinvar
SPTLC3	HGNC:16253	ENSG00000172296	Q9NUV7	Serine palmitoyltransferase 3	clinvar
FLVCR1	HGNC:24682	ENSG00000162769	Q9Y5Y0	Choline/ethanolamine transporter FLVCR1	clinvar
GJB1	HGNC:4283	ENSG00000169562	P08034	Gap junction beta-1 protein	clinvar
MPZ	HGNC:7225	ENSG00000158887	P25189	Myelin protein P0	clinvar
POMT1	HGNC:9202	ENSG00000130714	Q9Y6A1	Protein O-mannosyl-transferase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMPDL3A	Cyclic GMP-AMP phosphodiesterase SMPDL3A	Cyclic-nucleotide phosphodiesterase that acts as a negative regulator of innate immunity by mediating degradation of 2’,3’-cGAMP, thereby inhibiting the cGAS-STING signaling.
SCN11A	Sodium channel protein type 11 subunit alpha	Sodium channel mediating the voltage-dependent sodium ion permeability of excitable membranes.
GDAP1	Ganglioside-induced differentiation-associated protein 1	Regulates the mitochondrial network by promoting mitochondrial fission.
SPTLC3	Serine palmitoyltransferase 3	Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-…
FLVCR1	Choline/ethanolamine transporter FLVCR1	Uniporter that mediates the transport of extracellular choline and ethanolamine into cells, thereby playing a key role in phospholipid biosynthesis.
GJB1	Gap junction beta-1 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
MPZ	Myelin protein P0	Is an adhesion molecule necessary for normal myelination in the peripheral nervous system.
POMT1	Protein O-mannosyl-transferase 1	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.

Protein-family classification

Druggable: 6 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.75

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)	3	4.5×	0.118
Ion channel	1	13.9×	0.164
Transporter	1	9.7×	0.164
Antibody/Immunoglobulin	1	3.6×	0.304
Other/Unknown	2	0.5×	0.984

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMPDL3A	Enzyme (other)	yes	3.1.4.1	Calcineurin-like_PHP, ASM-like_Pdiesterase_prd, Metallo-depent_PP-like
SCN11A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
GDAP1	Other/Unknown	no		Glutathione_S-Trfase_N, Glutathione-S-Trfase_C-like, GST_C_GDAP1
SPTLC3	Enzyme (other)	yes	2.3.1.50	Aminotrans_II_pyridoxalP_BS, Aminotransferase_I/II_large, PyrdxlP-dep_Trfase_major
FLVCR1	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
GJB1	Other/Unknown	no		Connexin, Connexin32, Connexin_N
MPZ	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom
POMT1	Enzyme (other)	yes	2.4.1.109	ArnT-like_N, MIR_motif, PMT-like

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	2
colonic mucosa	1
mucosa of sigmoid colon	1
upper leg skin	1
dorsal root ganglion	1
male germ line stem cell (sensu Vertebrata) in testis	1
endothelial cell	1
oocyte	1
secondary oocyte	1
placenta	1
skin of abdomen	1
epithelial cell of pancreas	1
ileal mucosa	1
jejunal mucosa	1
C1 segment of cervical spinal cord	1
liver	1
right lobe of liver	1
olfactory bulb	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMPDL3A	280	ubiquitous	marker	upper leg skin, mucosa of sigmoid colon, colonic mucosa
SCN11A	166	broad	marker	buccal mucosa cell, dorsal root ganglion, male germ line stem cell (sensu Vertebrata) in testis
GDAP1	244	ubiquitous	yes	endothelial cell, secondary oocyte, oocyte
SPTLC3	228	ubiquitous	marker	buccal mucosa cell, placenta, skin of abdomen
FLVCR1	240	ubiquitous	marker	jejunal mucosa, ileal mucosa, epithelial cell of pancreas
GJB1	207	broad	marker	right lobe of liver, C1 segment of cervical spinal cord, liver
MPZ	178	ubiquitous	marker	tibial nerve, sural nerve, olfactory bulb
POMT1	264	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTLC3	1,784
GJB1	1,494
POMT1	1,475
FLVCR1	1,348
GDAP1	1,249
SCN11A	1,202
SMPDL3A	522
MPZ	25

Intra-cohort edges

A	B	Sources
GDAP1	GJB1	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GJB1	P08034	15
GDAP1	Q8TB36	8
FLVCR1	Q9Y5Y0	8
SMPDL3A	Q92484	2
MPZ	P25189	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POMT1	Q9Y6A1	88.09
SPTLC3	Q9NUV7	87.25
SCN11A	Q9UI33	69.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 8 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
EGR2 and SOX10-mediated initiation of Schwann cell myelination	2	105.2×	0.004	GJB1, MPZ
Oligomerization of connexins into connexons	1	543.8×	0.009	GJB1
Transport of connexins along the secretory pathway	1	543.8×	0.009	GJB1
Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2	1	543.8×	0.009	POMT1
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	1	543.8×	0.009	POMT1
DAG1 core M1 glycosylations	1	407.9×	0.010	POMT1
DAG1 core M2 glycosylations	1	326.3×	0.011	POMT1
DAG1 core M3 glycosylations	1	271.9×	0.011	POMT1
Heme biosynthesis	1	108.8×	0.025	FLVCR1
Nervous system development	2	12.3×	0.026	SCN11A, MPZ
Class I peroxisomal membrane protein import	1	74.2×	0.030	GDAP1
Interaction between L1 and Ankyrins	1	52.6×	0.034	SCN11A
Phase 0 - rapid depolarisation	1	49.4×	0.034	SCN11A
Iron uptake and transport	1	49.4×	0.034	FLVCR1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	48.0×	0.034	POMT1
Gap junction assembly	1	41.8×	0.036	GJB1
Sphingolipid de novo biosynthesis	1	40.8×	0.036	SPTLC3
Sphingolipid metabolism	1	24.0×	0.057	SPTLC3
L1CAM interactions	1	17.2×	0.075	SCN11A
Cardiac conduction	1	15.5×	0.078	SCN11A
Developmental Biology	2	4.1×	0.095	SCN11A, MPZ
Muscle contraction	1	11.0×	0.099	SCN11A
Axon guidance	1	6.5×	0.158	SCN11A
Metabolism of lipids	1	4.5×	0.210	SPTLC3
Metabolism	1	1.7×	0.468	SPTLC3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sphingoid biosynthetic process	1	2106.5×	0.009	SPTLC3
reflex	1	2106.5×	0.009	SCN11A
small intestine smooth muscle contraction	1	2106.5×	0.009	SCN11A
thermosensory behavior	1	1053.2×	0.009	SCN11A
behavioral response to acetic acid induced pain	1	1053.2×	0.009	SCN11A
cell aggregation	1	1053.2×	0.009	MPZ
response to high light intensity	1	702.2×	0.009	SCN11A
micturition	1	702.2×	0.009	SCN11A
behavioral response to formalin induced pain	1	702.2×	0.009	SCN11A
heme export	1	702.2×	0.009	FLVCR1
action potential initiation	1	702.2×	0.009	SCN11A
thigmotaxis	1	526.6×	0.011	SCN11A
heme transport	1	526.6×	0.011	FLVCR1
nucleoside triphosphate catabolic process	1	421.3×	0.012	SMPDL3A
response to nitric oxide	1	421.3×	0.012	SCN11A
calcitonin gene-related peptide receptor signaling pathway	1	351.1×	0.013	SCN11A
gap junction assembly	1	263.3×	0.014	GJB1
regulation of organ growth	1	263.3×	0.014	FLVCR1
head morphogenesis	1	263.3×	0.014	FLVCR1
skeletal muscle organ development	1	263.3×	0.014	SCN11A
sensory perception of itch	1	234.1×	0.014	SCN11A
acute inflammatory response	1	210.7×	0.014	SCN11A
chronic inflammatory response	1	210.7×	0.014	SCN11A
membrane depolarization during action potential	1	210.7×	0.014	SCN11A
choline transport	1	191.5×	0.014	FLVCR1
cellular response to vitamin D	1	191.5×	0.014	GDAP1
response to prostaglandin E	1	175.5×	0.014	SCN11A
artery development	1	175.5×	0.014	SCN11A
cAMP/PKA signal transduction	1	175.5×	0.014	SCN11A
mitochondrial transport	1	150.5×	0.015	FLVCR1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 7

Druggability breadth: 3 of 8 evidence-associated genes (38%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN11A	15	4
SMPDL3A	0	0
GDAP1	0	0
SPTLC3	0	0
FLVCR1	0	0
GJB1	0	0
MPZ	0	0
POMT1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	SCN11A
SERTINDOLE	4	SCN11A
PIMOZIDE	4	SCN11A
NIFEDIPINE	4	SCN11A
DILTIAZEM	4	SCN11A
MIBEFRADIL	4	SCN11A
HALOPERIDOL	4	SCN11A
MEXILETINE	4	SCN11A
AMITRIPTYLINE	4	SCN11A
AMIODARONE	4	SCN11A
CHLORPROMAZINE	4	SCN11A
TEDISAMIL	3	SCN11A
NITRENDIPINE	3	SCN11A
AJMALINE	3	SCN11A
CIFENLINE	2	SCN11A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
SCN11A	33	Functional:16, Binding:15, ADMET:2
SPTLC3	1	Binding:1
GJB1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SMPDL3A	3.1.4.1, 3.1.4.12	phosphodiesterase I, sphingomyelin phosphodiesterase
SPTLC3	2.3.1.50	serine C-palmitoyltransferase
POMT1	2.4.1.109	dolichyl-phosphate-mannose-protein mannosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

15 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	SCN11A
SERTINDOLE	4	SCN11A
PIMOZIDE	4	SCN11A
NIFEDIPINE	4	SCN11A
DILTIAZEM	4	SCN11A
MIBEFRADIL	4	SCN11A
HALOPERIDOL	4	SCN11A
MEXILETINE	4	SCN11A
AMITRIPTYLINE	4	SCN11A
AMIODARONE	4	SCN11A
CHLORPROMAZINE	4	SCN11A
TEDISAMIL	3	SCN11A
NITRENDIPINE	3	SCN11A
AJMALINE	3	SCN11A
CIFENLINE	2	SCN11A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN11A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	SMPDL3A, FLVCR1, MPZ
D	Druggable family + AlphaFold only, no drug	2	SPTLC3, POMT1
E	Difficult family or no structure, no drug	2	GDAP1, GJB1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMPDL3A	0	—
GDAP1	0	—
SPTLC3	1	—
FLVCR1	0	—
GJB1	1	—
MPZ	0	—
POMT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01526564	PHASE3	COMPLETED	Clinical Study on Acetyl-L-Carnitine
NCT01980368	Not specified	WITHDRAWN	Tai Chi Easy in Treating Cancer Survivors With Peripheral Sensory Neuropathy
NCT02539329	Not specified	COMPLETED	Characterization of Anti-FGFR3 Antibodies
NCT02565407	Not specified	COMPLETED	Robot-aided Proprioceptive Rehabilitation Training
NCT03538756	Not specified	COMPLETED	walk2Wellness: Long-term Effects of Walkasins® Wearable Sensory Prosthesis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ACETYLCARNITINE	3	1