Spastic paraplegia 93, autosomal recessive

Summary

Spastic paraplegia 93, autosomal recessive (MONDO:0975796) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic paraplegia 93, autosomal recessive
Mondo ID	MONDO:0975796
OMIM	620938
DOID	DOID:0070645
UMLS	C5975375
MedGen	1874905
GARD	0027316
Is cancer (heuristic)	no

Data availability: 15 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › palsy › paraplegia › hereditary spastic paraplegia › spastic paraplegia 93, autosomal recessive

Related subtypes (44): hereditary spastic paraplegia 3A, hereditary spastic paraplegia 4, mast syndrome, hereditary spastic paraplegia 5A, hereditary spastic paraplegia 16, hereditary spastic paraplegia 2, macrocephaly-spastic paraplegia-dysmorphism syndrome, Charcot-Marie-Tooth disease type 5, hereditary spastic paraplegia 6, hereditary spastic paraplegia 10, hereditary spastic paraplegia 14, hereditary spastic paraplegia 13, hereditary spastic paraplegia 7, hereditary spastic paraplegia 33, hereditary spastic paraplegia 31, hereditary spastic paraplegia 30, hereditary spastic paraplegia 35, hereditary spastic paraplegia 50, hereditary spastic paraplegia 48, hereditary spastic paraplegia 51, hereditary spastic paraplegia 47, hereditary spastic paraplegia 52, hereditary spastic paraplegia 56, early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, hereditary spastic paraplegia 77, pure hereditary spastic paraplegia, complex hereditary spastic paraplegia, pure or complex hereditary spastic paraplegia, spastic paraplegia 87, autosomal recessive, spastic paraplegia 80, autosomal dominant, spastic paraplegia 81, autosomal recessive, spastic paraplegia 82, autosomal recessive, spastic paraplegia 83, autosomal recessive, spastic paraplegia 88, autosomal dominant, spastic paraplegia 79A, autosomal dominant, with ataxia, spastic paraplegia 89, autosomal recessive, spastic paraplegia 90A, autosomal dominant, spastic paraplegia 90B, autosomal recessive, spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia, spastic paraplegia 72b, autosomal recessive, spastic paraplegia 92, autosomal recessive, IFIH1-related hereditary spastic paraplegia, RNASEH2B-related hereditary spastic paraplegia, ADAR-related hereditary spastic paraplegia

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

15 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 uncertain significance, 2 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031688	NM_001002755.4(NFU1):c.545G>A (p.Arg182Gln)	NFU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3338679	NFU1, 1-BP DEL, 146C	NFU1	Pathogenic	no assertion criteria provided
3338680	NM_001002755.4(NFU1):c.721G>C (p.Val241Leu)	NFU1	Pathogenic	no assertion criteria provided
3338683	NM_001002755.4(NFU1):c.362T>C (p.Val121Ala)	NFU1	Pathogenic	no assertion criteria provided
3338684	NM_001002755.4(NFU1):c.295C>G (p.Leu99Val)	NFU1	Pathogenic	no assertion criteria provided
3338685	NM_001002755.4(NFU1):c.263T>C (p.Phe88Ser)	NFU1	Pathogenic	no assertion criteria provided
3356228	NM_001002755.4(NFU1):c.62+89G>A	NFU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488563	NM_001002755.4(NFU1):c.545+5G>A	NFU1	Pathogenic	criteria provided, multiple submitters, no conflicts
1285476	NM_001002755.4(NFU1):c.565G>A (p.Gly189Arg)	NFU1	Likely pathogenic	criteria provided, single submitter
3299569	NM_001002755.4(NFU1):c.727G>A (p.Asp243Asn)	NFU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
336888	NM_001002755.4(NFU1):c.629G>T (p.Cys210Phe)	NFU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1207048	NM_001002755.4(NFU1):c.548C>G (p.Pro183Arg)	NFU1	Uncertain significance	criteria provided, single submitter
1214780	NM_001002755.4(NFU1):c.398T>C (p.Leu133Pro)	NFU1	Uncertain significance	criteria provided, single submitter
1303302	NM_001002755.4(NFU1):c.298G>C (p.Ala100Pro)	NFU1	Uncertain significance	criteria provided, single submitter
1303303	NM_001002755.4(NFU1):c.301A>G (p.Arg101Gly)	NFU1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NFU1	Orphanet:401869	Multiple mitochondrial dysfunctions syndrome 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
NFU1	HGNC:16287	ENSG00000169599	Q9UMS0	NFU1 iron-sulfur cluster scaffold homolog, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NFU1	NFU1 iron-sulfur cluster scaffold homolog, mitochondrial	Iron-sulfur cluster scaffold protein which can assemble [4Fe-4S] clusters and deliver them to target proteins.

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)
NFU1	Other/Unknown	no		NIF_FeS_clus_asmbl_NifU_C, Nfu/NifU_N, FSCA_dom_sf

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
biceps brachii	1
heart right ventricle	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NFU1	291	ubiquitous	marker	heart right ventricle, biceps brachii, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NFU1	1,832

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NFU1	Q9UMS0	2

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
Protein lipoylation	1	1038.2×	1e-03	NFU1

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
iron-sulfur cluster assembly	1	601.9×	0.003	NFU1
protein maturation	1	163.6×	0.006	NFU1

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
NFU1	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	NFU1

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)
NFU1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.