Spinal muscular atrophy, distal, autosomal recessive, 6

Summary

Spinal muscular atrophy, distal, autosomal recessive, 6 (MONDO:0859279) is a disease caused by REEP1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: REEP1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinal muscular atrophy, distal, autosomal recessive, 6
Mondo ID	MONDO:0859279
OMIM	620011
DOID	DOID:0081425
UMLS	C5774201
MedGen	1823974
GARD	0026685
Is cancer (heuristic)	no

Also known as: DSMA6

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › neuronopathy, distal hereditary motor, autosomal recessive › spinal muscular atrophy, distal, autosomal recessive, 6

Related subtypes (11): autosomal recessive distal spinal muscular atrophy 1, autosomal recessive distal spinal muscular atrophy 2, neuronopathy, distal hereditary motor, autosomal recessive 3, neuronopathy, distal hereditary motor, autosomal recessive 4, neuronopathy, distal hereditary motor, autosomal recessive 5, neuronopathy, distal hereditary motor, autosomal recessive 8, neuronopathy, distal hereditary motor, autosomal recessive 7, early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome, neuronopathy, distal hereditary motor, autosomal recessive 9, neuronopathy, distal hereditary motor, autosomal recessive 10, neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703514	NM_001371279.1(REEP1):c.124T>C (p.Trp42Arg)	REEP1	Pathogenic	no assertion criteria provided
217864	NM_001371279.1(REEP1):c.303+1_303+7delinsAC	REEP1	Pathogenic	no assertion criteria provided
1172760	NM_001371279.1(REEP1):c.248del (p.Gly83fs)	REEP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2047524	NM_001371279.1(REEP1):c.503C>T (p.Ser168Leu)	REEP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892272	NM_001371279.1(REEP1):c.84A>T (p.Lys28Asn)	REEP1	Uncertain significance	criteria provided, single submitter
932703	NM_001371279.1(REEP1):c.853T>G (p.Ter285Gly)	REEP1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
REEP1	Strong	Autosomal dominant	neuronopathy, distal hereditary motor, type 5B	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
REEP1	Orphanet:101011	Autosomal dominant spastic paraplegia type 31
REEP1	Orphanet:139536	Distal hereditary motor neuropathy type 5

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
REEP1	HGNC:25786	ENSG00000068615	Q9H902	Receptor expression-enhancing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
REEP1	Receptor expression-enhancing protein 1	Required for endoplasmic reticulum (ER) network formation, shaping and remodeling; it links ER tubules to the cytoskeleton.

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)
REEP1	Other/Unknown	no		TB2_DP1_HVA22

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
cortical plate	1
dorsal root ganglion	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
REEP1	284	broad	marker	dorsal root ganglion, middle temporal gyrus, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
REEP1	1,295

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
REEP1	Q9H902	67.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Expression and translocation of olfactory receptors	1	28.1×	0.036	REEP1

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
protein insertion into membrane	1	2106.5×	9e-04	REEP1
endoplasmic reticulum tubular network organization	1	1123.5×	9e-04	REEP1

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
REEP1	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	REEP1

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)
REEP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.