Mirror movements 1

Summary

Mirror movements 1 (MONDO:0008002) is a disease caused by DCC (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: DCC (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mirror movements 1
Mondo ID	MONDO:0008002
OMIM	157600
DOID	DOID:0070636
UMLS	C1834870
MedGen	320461
GARD	0015086
Is cancer (heuristic)	no

Also known as: DCC familial congenital mirror movements · familial congenital mirror movements caused by mutation in DCC · mirror movements 1 · mirror movements type 1 · MRMV1

Data availability: 50 ClinVar variants · 4 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 1 and/or agenesis of the corpus callosum › mirror movements 1

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

50 retrieved; paginated sample, class counts are floors:

17 pathogenic, 9 uncertain significance, 7 likely pathogenic, 7 benign, 4 not provided, 4 benign/likely benign, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1300257	NM_005215.4(DCC):c.2774dup (p.Asn925fs)	DCC	Pathogenic	no assertion criteria provided
1676259	NM_005215.4(DCC):c.2266C>T (p.Arg756Ter)	DCC	Pathogenic	criteria provided, single submitter
187795	NM_005215.4(DCC):c.571dup (p.Val191fs)	DCC	Pathogenic	no assertion criteria provided
187796	NM_005215.4(DCC):c.823C>T (p.Arg275Ter)	DCC	Pathogenic	criteria provided, multiple submitters, no conflicts
187797	NM_005215.4(DCC):c.1140+1G>A	DCC	Pathogenic	criteria provided, single submitter
187800	NM_005215.4(DCC):c.3836_3837del (p.Leu1279fs)	DCC	Pathogenic	no assertion criteria provided
187801	NM_005215.3(DCC):c.698-?_985+?del (p.Asp233_Leu328del)	DCC	Pathogenic	no assertion criteria provided
2429879	NM_005215.4(DCC):c.1154T>A (p.Leu385Ter)	DCC	Pathogenic	criteria provided, single submitter
2626888	NM_005215.4(DCC):c.2280_2286del (p.Ile760fs)	DCC	Pathogenic	criteria provided, single submitter
3376699	NM_005215.4(DCC):c.2377_2381del (p.Val793fs)	DCC	Pathogenic	criteria provided, single submitter
3377513	NM_005215.4(DCC):c.3577C>T (p.Gln1193Ter)	DCC	Pathogenic	criteria provided, single submitter
375281	NM_005215.4(DCC):c.925del (p.Thr309fs)	DCC	Pathogenic	no assertion criteria provided
375282	NM_005215.4(DCC):c.2378T>G (p.Val793Gly)	DCC	Pathogenic	no assertion criteria provided
375283	NM_005215.4(DCC):c.2414G>A (p.Gly805Glu)	DCC	Pathogenic	no assertion criteria provided
3899221	NM_005215.4(DCC):c.278C>A (p.Ser93Ter)	DCC	Pathogenic	criteria provided, single submitter
446724	NM_005215.4(DCC):c.788_794del (p.Val263fs)	DCC	Pathogenic	criteria provided, single submitter
4845332	NM_005215.4(DCC):c.2690C>G (p.Ser897Ter)	DCC	Pathogenic	criteria provided, single submitter
1027397	NM_005215.4(DCC):c.3073C>T (p.Arg1025Ter)	DCC	Likely pathogenic	criteria provided, single submitter
1710471	NM_005215.4(DCC):c.2034_2038del (p.Asn678fs)	DCC	Likely pathogenic	criteria provided, single submitter
2412758	NM_005215.4(DCC):c.1256del (p.Lys419fs)	DCC	Likely pathogenic	criteria provided, single submitter
2412759	NM_005215.4(DCC):c.2304C>G (p.Tyr768Ter)	DCC	Likely pathogenic	criteria provided, single submitter
2576977	NM_005215.4(DCC):c.3778C>T (p.Gln1260Ter)	DCC	Likely pathogenic	criteria provided, single submitter
2692449	NM_005215.4(DCC):c.2551C>T (p.Gln851Ter)	DCC	Likely pathogenic	criteria provided, single submitter
3600486	NM_005215.4(DCC):c.2216_2217dup (p.Cys740fs)	DCC	Likely pathogenic	criteria provided, single submitter
187790	NM_005215.4(DCC):c.1409G>A (p.Gly470Asp)	DCC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
187792	NM_005215.4(DCC):c.2105A>G (p.Asn702Ser)	DCC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029949	NM_005215.4(DCC):c.2316_2317delinsAA (p.Arg773Ser)	DCC	Uncertain significance	criteria provided, single submitter
1031521	NM_005215.4(DCC):c.2624C>T (p.Thr875Met)	DCC	Uncertain significance	criteria provided, single submitter
187793	NM_005215.4(DCC):c.2407G>A (p.Gly803Arg)	DCC	Uncertain significance	criteria provided, multiple submitters, no conflicts
1992322	NM_005215.4(DCC):c.2220CAT[2] (p.Ile742del)	DCC	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
DCC	Definitive	Autosomal dominant	mirror movements 1	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCC	Orphanet:238722	Familial congenital mirror movements
DCC	Orphanet:2744	Horizontal gaze palsy with progressive scoliosis
DCC	Orphanet:478	Kallmann syndrome
NTN1	Orphanet:238722	Familial congenital mirror movements

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
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	gencc,clinvar
NTN1	HGNC:8029	ENSG00000065320	O95631	Netrin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
NTN1	Netrin-1	Netrins control guidance of CNS commissural axons and peripheral motor axons.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
NTN1	Other/Unknown	no		Netrin_domain, LE_dom, Laminin_N

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
cortical plate	1
left testis	1
right testis	1
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
DCC	154	broad	marker	cortical plate, right testis, left testis
NTN1	218	broad	marker	mucosa of stomach, right atrium auricular region, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NTN1	2,072
DCC	1,333

Intra-cohort edges

A	B	Sources
DCC	NTN1	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCC	P43146	9
NTN1	O95631	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
DSCAM interactions	2	2284.0×	2e-06	DCC, NTN1
Netrin mediated repulsion signals	2	1268.9×	3e-06	DCC, NTN1
Role of second messengers in netrin-1 signaling	2	1038.2×	3e-06	DCC, NTN1
Regulation of commissural axon pathfinding by SLIT and ROBO	2	951.7×	3e-06	DCC, NTN1
DCC mediated attractive signaling	2	713.8×	4e-06	DCC, NTN1
Netrin-1 signaling	2	439.2×	9e-06	DCC, NTN1
Caspase activation via Dependence Receptors in the absence of ligand	1	571.0×	0.003	DCC
Signaling by ROBO receptors	1	62.1×	0.022	NTN1
Axon guidance	1	22.6×	0.051	NTN1
Nervous system development	1	21.5×	0.051	NTN1
Developmental Biology	1	7.2×	0.134	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
anterior/posterior axon guidance	2	2808.7×	3e-06	DCC, NTN1
cell-cell adhesion	2	101.5×	0.001	DCC, NTN1
regulation of glial cell migration	1	4213.0×	0.002	NTN1
spinal cord ventral commissure morphogenesis	1	2808.7×	0.002	DCC
Cdc42 protein signal transduction	1	2106.5×	0.002	NTN1
dorsal/ventral axon guidance	1	2106.5×	0.002	DCC
chemorepulsion of axon	1	2106.5×	0.002	NTN1
mammary gland duct morphogenesis	1	1203.7×	0.003	NTN1
negative regulation of dendrite development	1	1053.2×	0.003	DCC
motor neuron migration	1	842.6×	0.003	NTN1
substrate-dependent cell migration, cell extension	1	766.0×	0.003	NTN1
negative regulation of collateral sprouting	1	766.0×	0.003	DCC
apoptotic process	2	28.7×	0.003	DCC, NTN1
glial cell proliferation	1	443.5×	0.004	NTN1
positive regulation of cell motility	1	383.0×	0.004	NTN1
nuclear migration	1	366.4×	0.004	NTN1
negative regulation of axon extension	1	366.4×	0.004	NTN1
regulation of synapse assembly	1	351.1×	0.004	NTN1
positive regulation of glial cell proliferation	1	351.1×	0.004	NTN1
postsynaptic modulation of chemical synaptic transmission	1	337.0×	0.004	DCC
positive regulation of axon extension	1	255.3×	0.005	NTN1
inner ear morphogenesis	1	150.5×	0.008	NTN1
negative regulation of neuron projection development	1	118.7×	0.010	DCC
Ras protein signal transduction	1	102.8×	0.011	NTN1
axonogenesis	1	80.2×	0.014	DCC
neuron migration	1	66.9×	0.016	DCC
axon guidance	1	45.3×	0.023	DCC
regulation of transcription by RNA polymerase II	1	5.8×	0.164	NTN1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DCC	0	0
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: 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	1	DCC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NTN1

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)
DCC	0	—
NTN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.