Mirror movements 4

Summary

Mirror movements 4 (MONDO:0032641) is a disease caused by NTN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NTN1 (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	mirror movements 4
Mondo ID	MONDO:0032641
OMIM	618264
DOID	DOID:0070638
UMLS	C4748869
MedGen	1648342
GARD	0016333
Is cancer (heuristic)	no

Also known as: MRMV4

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

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › familial congenital mirror movements › mirror movements 4

Related subtypes (3): mirror movements 2, mirror movements 3, mirror movements 1 and/or agenesis of the corpus callosum

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, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
599324	NM_004822.3(NTN1):c.1801T>C (p.Cys601Arg)	NTN1	Pathogenic	no assertion criteria provided
599325	NM_004822.3(NTN1):c.1549ATC[1] (p.Ile518del)	NTN1	Pathogenic	no assertion criteria provided
599326	NM_004822.3(NTN1):c.1802G>C (p.Cys601Ser)	NTN1	Pathogenic	no assertion criteria provided
3068079	NM_004822.3(NTN1):c.1789AAG[1] (p.Lys598del)	NTN1	Uncertain significance	criteria provided, single submitter
3891863	NM_004822.3(NTN1):c.1366G>A (p.Val456Ile)	NTN1	Uncertain significance	criteria provided, single submitter
3891864	NM_004822.3(NTN1):c.485A>G (p.Tyr162Cys)	NTN1	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
NTN1	Strong	Autosomal dominant	mirror movements 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NTN1	Orphanet:238722	Familial congenital mirror movements

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
NTN1	HGNC:8029	ENSG00000065320	O95631	Netrin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NTN1	Netrin-1	Netrins control guidance of CNS commissural axons and peripheral motor axons.

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)
NTN1	Other/Unknown	no		Netrin_domain, LE_dom, Laminin_N

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
lower esophagus muscularis layer	1
mucosa of stomach	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NTN1	218	broad	marker	mucosa of stomach, right atrium auricular region, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NTN1	2,072

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NTN1	O95631	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
DSCAM interactions	1	2284.0×	0.003	NTN1
Netrin mediated repulsion signals	1	1268.9×	0.003	NTN1
Role of second messengers in netrin-1 signaling	1	1038.2×	0.003	NTN1
Regulation of commissural axon pathfinding by SLIT and ROBO	1	951.7×	0.003	NTN1
DCC mediated attractive signaling	1	713.8×	0.003	NTN1
Netrin-1 signaling	1	439.2×	0.004	NTN1
Signaling by ROBO receptors	1	124.1×	0.012	NTN1
Axon guidance	1	45.1×	0.026	NTN1
Nervous system development	1	42.9×	0.026	NTN1
Developmental Biology	1	14.5×	0.069	NTN1

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
regulation of glial cell migration	1	8426.0×	0.002	NTN1
Cdc42 protein signal transduction	1	4213.0×	0.002	NTN1
chemorepulsion of axon	1	4213.0×	0.002	NTN1
anterior/posterior axon guidance	1	2808.7×	0.002	NTN1
mammary gland duct morphogenesis	1	2407.4×	0.002	NTN1
motor neuron migration	1	1685.2×	0.002	NTN1
substrate-dependent cell migration, cell extension	1	1532.0×	0.002	NTN1
glial cell proliferation	1	887.0×	0.002	NTN1
positive regulation of cell motility	1	766.0×	0.002	NTN1
nuclear migration	1	732.7×	0.002	NTN1
negative regulation of axon extension	1	732.7×	0.002	NTN1
regulation of synapse assembly	1	702.2×	0.002	NTN1
positive regulation of glial cell proliferation	1	702.2×	0.002	NTN1
positive regulation of axon extension	1	510.7×	0.003	NTN1
inner ear morphogenesis	1	300.9×	0.004	NTN1
Ras protein signal transduction	1	205.5×	0.006	NTN1
cell-cell adhesion	1	101.5×	0.011	NTN1
apoptotic process	1	28.7×	0.037	NTN1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	NTN1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
NTN1	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
NTN1	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	1	NTN1

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)
NTN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.