Periodic paralysis with later-onset distal motor neuropathy

Summary

Periodic paralysis with later-onset distal motor neuropathy (MONDO:0018343) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	periodic paralysis with later-onset distal motor neuropathy
Mondo ID	MONDO:0018343
Orphanet	397750
UMLS	C4751573
MedGen	1670241
GARD	0021634
Is cancer (heuristic)	no

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn metal metabolism disorder › familial periodic paralysis › periodic paralysis with later-onset distal motor neuropathy

Related subtypes (5): Andersen-Tawil syndrome, hypokalemic periodic paralysis, hyperkalemic periodic paralysis, normokalemic periodic paralysis, thyrotoxic periodic paralysis

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 10 · 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
MT-ATP6	Supportive	Mitochondrial	Leber hereditary optic neuropathy	8
MT-ATP8	Supportive	Mitochondrial	periodic paralysis with later-onset distal motor neuropathy	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-ATP6	Orphanet:104	Leber hereditary optic neuropathy
MT-ATP6	Orphanet:225154	Familial infantile bilateral striatal necrosis
MT-ATP6	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ATP6	Orphanet:320360	MT-ATP6-related mitochondrial spastic paraplegia
MT-ATP6	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP6	Orphanet:644	NARP syndrome
MT-ATP8	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP8	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP8	Orphanet:480	Kearns-Sayre syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MT-ATP6	HGNC:7414	ENSG00000198899	P00846	ATP synthase F(0) complex subunit a	gencc
MT-ATP8	HGNC:7415	ENSG00000228253	P03928	ATP synthase F(0) complex subunit 8	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MT-ATP6	ATP synthase F(0) complex subunit a	Subunit a, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of th…
MT-ATP8	ATP synthase F(0) complex subunit 8	Subunit 8, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of th…

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)
MT-ATP6	Other/Unknown	no		ATP_synth_F0_asu, ATP_synth_F0_asu_AS, F0_ATP_A_sf
MT-ATP8	Other/Unknown	no		ATP8_metazoa, ATP8_mammal

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
descending thoracic aorta	1
left uterine tube	1
mucosa of stomach	1
gastrocnemius	1
right lung	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-ATP6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, descending thoracic aorta
MT-ATP8	134		marker	gastrocnemius, right ovary, right lung

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-ATP6	2,869
MT-ATP8	916

Intra-cohort edges

A	B	Sources
MT-ATP6	MT-ATP8	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-ATP6	P00846	10
MT-ATP8	P03928	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of ATP by chemiosmotic coupling	2	571.0×	3e-05	MT-ATP6, MT-ATP8
Cristae formation	2	346.1×	4e-05	MT-ATP6, MT-ATP8
Mitochondrial biogenesis	2	167.9×	1e-04	MT-ATP6, MT-ATP8
Mitochondrial translation termination	2	109.8×	2e-04	MT-ATP6, MT-ATP8
Aerobic respiration and respiratory electron transport	2	88.5×	2e-04	MT-ATP6, MT-ATP8
Organelle biogenesis and maintenance	2	66.0×	3e-04	MT-ATP6, MT-ATP8
Metabolism	2	11.6×	0.010	MT-ATP6, MT-ATP8
Mitochondrial protein degradation	1	57.1×	0.020	MT-ATP6
Metabolism of proteins	1	6.2×	0.155	MT-ATP6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
proton motive force-driven ATP synthesis	2	802.5×	6e-06	MT-ATP6, MT-ATP8
proton motive force-driven mitochondrial ATP synthesis	2	263.3×	3e-05	MT-ATP6, MT-ATP8
response to hyperoxia	1	561.7×	0.002	MT-ATP6
proton transmembrane transport	1	156.0×	0.006	MT-ATP6

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MT-ATP6	0	0
MT-ATP8	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
MT-ATP6	1	Binding:1
MT-ATP8	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	MT-ATP6, MT-ATP8

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)
MT-ATP6	1	—
MT-ATP8	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.