Spastic paraplegia 82, autosomal recessive

Summary

Spastic paraplegia 82, autosomal recessive (MONDO:0032906) is a disease caused by PCYT2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PCYT2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic paraplegia 82, autosomal recessive
Mondo ID	MONDO:0032906
OMIM	618770
Orphanet	631073
DOID	DOID:0112343
UMLS	C5394037
MedGen	1710411
GARD	0025771
Is cancer (heuristic)	no

Also known as: autosomal recessive spastic paraplegia type 82 · spastic paraplegia 82, autosomal recessive · SPG82

Data availability: 17 ClinVar variants · 4 GenCC gene-disease records.

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 82, 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 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, spastic paraplegia 93, 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

17 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
3024149	NM_002861.5(PCYT2):c.1058+1G>A	PCYT2	Pathogenic	no assertion criteria provided
3024150	NM_002861.5(PCYT2):c.689T>A (p.Val230Glu)	PCYT2	Pathogenic	no assertion criteria provided
812573	NM_002861.5(PCYT2):c.1075C>T (p.Arg359Ter)	PCYT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3256733	NM_002861.5(PCYT2):c.88T>G (p.Cys30Gly)	LOC130061984	Likely pathogenic	no assertion criteria provided
2500196	NM_002861.5(PCYT2):c.903G>C (p.Lys301Asn)	PCYT2	Likely pathogenic	criteria provided, single submitter
2575242	NM_002861.5(PCYT2):c.682G>A (p.Gly228Arg)	PCYT2	Likely pathogenic	criteria provided, single submitter
2627104	NM_002861.5(PCYT2):c.969+5G>A	PCYT2	Likely pathogenic	criteria provided, single submitter
3068607	NM_002861.5(PCYT2):c.781A>T (p.Lys261Ter)	PCYT2	Likely pathogenic	criteria provided, single submitter
4277682	NM_002861.5(PCYT2):c.418C>T (p.Arg140Cys)	PCYT2	Likely pathogenic	criteria provided, single submitter
812572	NM_002861.5(PCYT2):c.676C>T (p.His226Tyr)	PCYT2	Likely pathogenic	criteria provided, single submitter
3027448	NM_002861.5(PCYT2):c.683G>A (p.Gly228Glu)	PCYT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1329483	NM_002861.5(PCYT2):c.1009G>A (p.Gly337Ser)	PCYT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1329485	NM_002861.5(PCYT2):c.555C>A (p.Asn185Lys)	PCYT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434618	NM_002861.5(PCYT2):c.175G>T (p.Asp59Tyr)	PCYT2	Uncertain significance	criteria provided, single submitter
3775516	NM_002861.5(PCYT2):c.760-80C>T	PCYT2	Uncertain significance	criteria provided, single submitter
3896939	NM_002861.5(PCYT2):c.749A>G (p.His250Arg)	PCYT2	Uncertain significance	criteria provided, single submitter
812571	NM_002861.5(PCYT2):c.866C>T (p.Pro289Leu)	PCYT2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PCYT2	Definitive	Autosomal recessive	spastic paraplegia 82, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PCYT2	Orphanet:631073	Autosomal recessive spastic paraplegia type 82

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
PCYT2	HGNC:8756	ENSG00000185813	Q99447	Ethanolamine-phosphate cytidylyltransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PCYT2	Ethanolamine-phosphate cytidylyltransferase	Ethanolamine-phosphate cytidylyltransferase that catalyzes the second step in the synthesis of phosphatidylethanolamine (PE) from ethanolamine via the CDP-ethanolamine pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PCYT2	Enzyme (other)	yes	2.7.7.14	Cyt_trans-like, Rossmann-like_a/b/a_fold, CCT

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
left testis	1
right lobe of liver	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PCYT2	265	ubiquitous	marker	left testis, right testis, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCYT2	1,698

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PCYT2	Q99447	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
Synthesis of PE	1	878.5×	0.001	PCYT2

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
phosphatidylethanolamine biosynthetic process	1	1872.4×	0.001	PCYT2
phospholipid biosynthetic process	1	674.1×	0.001	PCYT2

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
PCYT2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PCYT2	2.7.7.14	ethanolamine-phosphate cytidylyltransferase

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	1	PCYT2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
PCYT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.