neuropathy, hereditary sensory, type 1D

Summary

neuropathy, hereditary sensory, type 1D (MONDO:0013381) is a disease caused by ATL1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ATL1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 42

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuropathy, hereditary sensory, type 1D
Mondo ID	MONDO:0013381
OMIM	613708
DOID	DOID:0070156
UMLS	C3150972
MedGen	462322
GARD	0015695
Is cancer (heuristic)	no

Also known as: HSN1D · neuropathy, hereditary sensory, type ID

Data availability: 42 ClinVar variants · 4 GenCC gene-disease records.

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 1 › neuropathy, hereditary sensory, type 1D

Related subtypes (5): neuropathy, hereditary sensory and autonomic, type 1A, neuropathy, hereditary sensory and autonomic, type 1C, hereditary sensory neuropathy-deafness-dementia syndrome, neuropathy, hereditary sensory, type 1F, cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome

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

42 retrieved; paginated sample, class counts are floors:

13 benign/likely benign, 11 benign, 8 uncertain significance, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 pathogenic, 1 not provided, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30579	NM_015915.5(ATL1):c.1065C>A (p.Asn355Lys)	ATL1	Pathogenic	criteria provided, single submitter
4346	NM_015915.5(ATL1):c.715C>T (p.Arg239Cys)	ATL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3338470	GRCh37/hg19 14q22.1(chr14:50911699-51132124)x4	ATL1	Likely pathogenic	no assertion criteria provided
3576592	NM_015915.5(ATL1):c.940G>T (p.Glu314Ter)	ATL1	Likely pathogenic	criteria provided, single submitter
638382	NM_015915.5(ATL1):c.1111dup (p.Met371fs)	ATL1	Likely pathogenic	criteria provided, single submitter
30580	NM_015915.5(ATL1):c.196G>C (p.Glu66Gln)	ATL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30582	NM_015915.5(ATL1):c.1246C>T (p.Arg416Cys)	ATL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
425042	NM_015915.5(ATL1):c.922G>A (p.Glu308Lys)	ATL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
637513	NM_015915.5(ATL1):c.976del (p.Val326fs)	ATL1	Conflicting classifications of pathogenicity	no assertion criteria provided
1402624	NM_015915.5(ATL1):c.723+3_723+19del	ATL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3383045	NM_015915.5(ATL1):c.1006T>C (p.Tyr336His)	ATL1	Uncertain significance	criteria provided, single submitter
444328	NM_015915.5(ATL1):c.688G>A (p.Asp230Asn)	ATL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
538582	NM_015915.5(ATL1):c.1556G>A (p.Ser519Asn)	ATL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
857576	NM_015915.5(ATL1):c.1355T>C (p.Phe452Ser)	ATL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
930242	NM_015915.5(ATL1):c.169C>T (p.Leu57Phe)	ATL1	Uncertain significance	criteria provided, single submitter
931613	NM_015915.5(ATL1):c.833C>T (p.Thr278Ile)	ATL1	Uncertain significance	criteria provided, single submitter
976249	NM_015915.5(ATL1):c.1634C>T (p.Pro545Leu)	ATL1	Uncertain significance	criteria provided, single submitter
1174932	NM_015915.5(ATL1):c.418-19G>T	ATL1	Benign	criteria provided, multiple submitters, no conflicts
1278312	NM_015915.5(ATL1):c.1552-24_1552-20del	ATL1	Benign	criteria provided, multiple submitters, no conflicts
1293178	NM_015915.5(ATL1):c.1552-68_1552-67insATA	ATL1	Benign	criteria provided, multiple submitters, no conflicts
136428	NM_015915.5(ATL1):c.630+7G>A	ATL1	Benign	criteria provided, multiple submitters, no conflicts
21530	NM_015915.5(ATL1):c.351G>A (p.Glu117=)	ATL1	Benign	criteria provided, multiple submitters, no conflicts
21533	NM_015915.5(ATL1):c.621G>A (p.Lys207=)	ATL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
21534	NM_015915.5(ATL1):c.84A>G (p.Pro28=)	ATL1	Benign	criteria provided, multiple submitters, no conflicts
241074	NM_015915.5(ATL1):c.1230G>A (p.Gly410=)	ATL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
313293	NM_015915.5(ATL1):c.408T>C (p.Asp136=)	ATL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
313294	NM_015915.5(ATL1):c.417+3A>G	ATL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
313298	NM_015915.5(ATL1):c.669C>T (p.Tyr223=)	ATL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
313299	NM_015915.5(ATL1):c.693T>C (p.Gly231=)	ATL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
313300	NM_015915.5(ATL1):c.705C>T (p.Phe235=)	ATL1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
ATL1	Definitive	Autosomal dominant	neuropathy, hereditary sensory, type 1D	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATL1	Orphanet:100984	Autosomal dominant spastic paraplegia type 3
ATL1	Orphanet:36386	Hereditary sensory and autonomic neuropathy type 1

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
ATL1	HGNC:11231	ENSG00000198513	Q8WXF7	Atlastin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATL1	Atlastin-1	Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network.

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)
ATL1	Other/Unknown	no		Guanylate-bd_N, P-loop_NTPase, G_GB1_RHD3_dom

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
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATL1	241	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATL1	1,206

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATL1	Q8WXF7	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
endoplasmic reticulum membrane fusion	1	3370.4×	0.001	ATL1
endoplasmic reticulum tubular network membrane organization	1	2106.5×	0.001	ATL1
endoplasmic reticulum organization	1	421.3×	0.004	ATL1
axonogenesis	1	160.5×	0.008	ATL1
protein homooligomerization	1	122.1×	0.008	ATL1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	ATL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.