neuropathy, hereditary sensory, type 1F

Summary

neuropathy, hereditary sensory, type 1F (MONDO:0014286) is a disease caused by ATL3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ATL3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 483

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuropathy, hereditary sensory, type 1F
Mondo ID	MONDO:0014286
OMIM	615632
DOID	DOID:0070154
UMLS	C3810194
MedGen	816524
GARD	0015995
Is cancer (heuristic)	no

Also known as: ATL3 hereditary sensory and autonomic neuropathy type 1 · hereditary sensory and autonomic neuropathy type 1 caused by mutation in ATL3 · HSN1F · neuropathy, hereditary sensory, type 1F · neuropathy, hereditary sensory, type IF

Data availability: 483 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 1F

Related subtypes (5): neuropathy, hereditary sensory and autonomic, type 1A, neuropathy, hereditary sensory and autonomic, type 1C, neuropathy, hereditary sensory, type 1D, hereditary sensory neuropathy-deafness-dementia syndrome, 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

483 retrieved; paginated sample, class counts are floors:

263 uncertain significance, 168 likely benign, 22 conflicting classifications of pathogenicity, 18 benign, 9 benign/likely benign, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
932960	NM_015459.5(ATL3):c.1013C>G (p.Pro338Arg)	ATL3	Pathogenic	no assertion criteria provided
97070	NM_015459.5(ATL3):c.575A>G (p.Tyr192Cys)	ATL3	Pathogenic	no assertion criteria provided
3895483	NM_015459.5(ATL3):c.1046_1066dup (p.Ala355_Ala356insGluAlaAsnAsnLeuAlaAla)	ATL3	Likely pathogenic	criteria provided, single submitter
1014961	NM_015459.5(ATL3):c.710A>G (p.Gln237Arg)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1046971	NM_015459.5(ATL3):c.1382C>T (p.Thr461Ile)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1056650	NM_015459.5(ATL3):c.935A>G (p.Asn312Ser)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1403285	NM_015459.5(ATL3):c.1138C>T (p.Pro380Ser)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1435475	NM_015459.5(ATL3):c.1413G>T (p.Gln471His)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1440813	NM_015459.5(ATL3):c.280A>G (p.Asn94Asp)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1509277	NM_015459.5(ATL3):c.1108G>T (p.Val370Phe)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1631858	NM_015459.5(ATL3):c.1500C>T (p.Gly500=)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1769970	NM_015459.5(ATL3):c.1324C>T (p.Arg442Ter)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2641900	NM_015459.5(ATL3):c.14A>G (p.Gln5Arg)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2851199	NM_015459.5(ATL3):c.774C>T (p.Ser258=)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
474835	NM_015459.5(ATL3):c.1501G>A (p.Gly501Arg)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541677	NM_015459.5(ATL3):c.581G>A (p.Arg194His)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541678	NM_015459.5(ATL3):c.1451T>C (p.Leu484Pro)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541683	NM_015459.5(ATL3):c.10C>T (p.Pro4Ser)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
569241	NM_015459.5(ATL3):c.16C>T (p.Arg6Ter)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
643677	NM_015459.5(ATL3):c.1390A>G (p.Ile464Val)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
661890	NM_015459.5(ATL3):c.267A>C (p.Glu89Asp)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
806688	NM_015459.5(ATL3):c.138G>C (p.Leu46Phe)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
838683	NM_015459.5(ATL3):c.1165G>A (p.Glu389Lys)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
949476	NM_015459.5(ATL3):c.782C>A (p.Thr261Asn)	ATL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
649263	NM_015459.5(ATL3):c.1539G>A (p.Gln513=)	LNCROPM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004245	NM_015459.5(ATL3):c.533T>C (p.Ile178Thr)	ATL3	Uncertain significance	criteria provided, single submitter
1004273	NC_000011.9:g.(?63396781)(63403816_?)dup	ATL3	Uncertain significance	criteria provided, single submitter
1005683	NM_015459.5(ATL3):c.562-7T>A	ATL3	Uncertain significance	criteria provided, single submitter
1008466	NM_015459.5(ATL3):c.1426A>G (p.Met476Val)	ATL3	Uncertain significance	criteria provided, single submitter
1010160	NM_015459.5(ATL3):c.457G>A (p.Val153Met)	ATL3	Uncertain significance	criteria provided, single submitter

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
ATL3	Strong	Autosomal dominant	neuropathy, hereditary sensory, type 1F	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATL3	Orphanet:36386	Hereditary sensory and autonomic neuropathy type 1

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATL3	HGNC:24526	ENSG00000184743	Q6DD88	Atlastin-3	gencc,clinvar
LNCROPM	HGNC:58146	ENSG00000256789		lncRNA regulator of PLAAT3 mediated phospholipid metabolism	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATL3	Atlastin-3	Atlastin-3 (ATL3) 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: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATL3	Other/Unknown	no		Guanylate-bd/ATL_C, Guanylate-bd_N, P-loop_NTPase
LNCROPM	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
layer of synovial tissue	1
saphenous vein	1
upper arm skin	1
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATL3	255	ubiquitous	marker	upper arm skin, saphenous vein, layer of synovial tissue
LNCROPM	124		yes	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATL3	1,536
LNCROPM	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATL3	Q6DD88	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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×	9e-04	ATL3
endoplasmic reticulum tubular network membrane organization	1	2106.5×	9e-04	ATL3
endoplasmic reticulum organization	1	421.3×	0.003	ATL3
protein homooligomerization	1	122.1×	0.008	ATL3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATL3	0	0
LNCROPM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATL3	1	Binding:1

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	2	ATL3, LNCROPM

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATL3	1	—
LNCROPM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.