Duane retraction syndrome 2

Summary

Duane retraction syndrome 2 (MONDO:0011444) is a disease caused by CHN1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CHN1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Duane retraction syndrome 2
Mondo ID	MONDO:0011444
OMIM	604356
DOID	DOID:0061028
SNOMED CT	128083007
UMLS	C0751083
MedGen	196721
GARD	0009966
Is cancer (heuristic)	no

Also known as: CHN1 Duane retraction syndrome · Duane retraction syndrome 2 · Duane retraction syndrome caused by mutation in CHN1 · Duane retraction syndrome type 2 · Duane syndrome type 2 · DURS2

Data availability: 67 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Duane retraction syndrome › Duane retraction syndrome 2

Related subtypes (3): Duane retraction syndrome 3 with or without deafness, Duane syndrome type 1, Duane retraction syndrome with congenital deafness

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

67 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 13 pathogenic, 4 benign, 4 conflicting classifications of pathogenicity, 2 likely benign, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17550	NM_001822.7(CHN1):c.60A>T (p.Leu20Phe)	CHN1	Pathogenic	no assertion criteria provided
17551	NM_001822.7(CHN1):c.378T>G (p.Ile126Met)	CHN1	Pathogenic	no assertion criteria provided
17552	NM_001822.7(CHN1):c.427T>C (p.Tyr143His)	CHN1	Pathogenic	no assertion criteria provided
17553	NM_001822.7(CHN1):c.668C>T (p.Ala223Val)	CHN1	Pathogenic	no assertion criteria provided
17554	NM_001822.7(CHN1):c.682G>A (p.Gly228Ser)	CHN1	Pathogenic	no assertion criteria provided
17555	NM_001822.7(CHN1):c.755C>A (p.Pro252Gln)	CHN1	Pathogenic	no assertion criteria provided
17556	NM_001822.7(CHN1):c.937G>A (p.Glu313Lys)	CHN1	Pathogenic	no assertion criteria provided
29623	NM_001822.7(CHN1):c.422C>T (p.Pro141Leu)	CHN1	Pathogenic	no assertion criteria provided
559835	NM_001822.7(CHN1):c.661T>C (p.Tyr221His)	CHN1	Pathogenic	criteria provided, single submitter
224626	NM_005461.5(MAFB):c.440del (p.Gly147fs)	MAFB	Pathogenic	criteria provided, single submitter
224627	NM_005461.5(MAFB):c.644del (p.Gln215fs)	MAFB	Pathogenic	criteria provided, single submitter
224628	NM_005461.5(MAFB):c.803del (p.Asn268fs)	MAFB	Pathogenic	criteria provided, single submitter
224629	NC_000020.11:g.(?40687489)(40688460_?)del	MAFB	Pathogenic	criteria provided, single submitter
4072045	NM_001822.7(CHN1):c.428A>G (p.Tyr143Cys)	CHN1	Likely pathogenic	criteria provided, single submitter
709072	NM_001822.7(CHN1):c.588C>T (p.Asn196=)	CHN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
722100	NM_001822.7(CHN1):c.435C>T (p.His145=)	CHN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
725227	NM_001822.7(CHN1):c.237A>G (p.Pro79=)	CHN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931006	NM_001822.7(CHN1):c.962G>C (p.Arg321Thr)	CHN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2688777	NM_001822.7(CHN1):c.361T>G (p.Leu121Val)	CHN1	Uncertain significance	criteria provided, single submitter
29624	NM_001822.7(CHN1):c.754C>T (p.Pro252Ser)	CHN1	Uncertain significance	criteria provided, single submitter
3061808	NM_001822.7(CHN1):c.62A>G (p.Tyr21Cys)	CHN1	Uncertain significance	criteria provided, single submitter
332458	NM_001822.7(CHN1):c.*608A>G	CHN1	Uncertain significance	criteria provided, single submitter
332460	NM_001822.7(CHN1):c.*154G>A	CHN1	Uncertain significance	criteria provided, single submitter
332462	NM_001822.7(CHN1):c.1319A>G (p.Asp440Gly)	CHN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
332463	NM_001822.7(CHN1):c.964+6T>G	CHN1	Uncertain significance	criteria provided, single submitter
332467	NM_001822.7(CHN1):c.628-15C>T	CHN1	Uncertain significance	criteria provided, single submitter
332468	NM_001822.7(CHN1):c.500C>T (p.Thr167Ile)	CHN1	Uncertain significance	criteria provided, single submitter
332469	NM_001822.7(CHN1):c.432G>C (p.Glu144Asp)	CHN1	Uncertain significance	criteria provided, single submitter
332470	NM_001822.7(CHN1):c.-36C>T	CHN1	Uncertain significance	criteria provided, single submitter
332472	NM_001822.7(CHN1):c.-74C>T	CHN1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CHN1	Strong	Autosomal dominant	Duane retraction syndrome 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHN1	Orphanet:233	Duane retraction syndrome
MAFB	Orphanet:233	Duane retraction syndrome
MAFB	Orphanet:2774	Multicentric carpo-tarsal osteolysis with or without nephropathy
MAFB	Orphanet:529574	Duane retraction syndrome with congenital deafness

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
CHN1	HGNC:1943	ENSG00000128656	P15882	N-chimaerin	gencc,clinvar
MAFB	HGNC:6408	ENSG00000204103	Q9Y5Q3	Transcription factor MafB	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHN1	N-chimaerin	GTPase-activating protein for p21-rac and a phorbol ester receptor.
MAFB	Transcription factor MafB	Acts as a transcriptional activator or repressor.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · 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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHN1	Scaffold/PPI	no		RhoGAP_dom, SH2, PKC_DAG/PE
MAFB	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf

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
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
gingiva	1
renal glomerulus	1
skin of hip	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHN1	279	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
MAFB	277	ubiquitous	marker	renal glomerulus, skin of hip, gingiva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAFB	2,671
CHN1	1,091

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHN1	P15882	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAFB	Q9Y5Q3	63.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Activation of HOX genes during differentiation	1	219.6×	0.023	MAFB
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	45.7×	0.041	MAFB
CDC42 GTPase cycle	1	36.1×	0.041	CHN1
RAC1 GTPase cycle	1	30.5×	0.041	CHN1
Developmental Biology	1	7.2×	0.134	MAFB

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
rhombomere 6 development	1	8426.0×	0.002	MAFB
rhombomere 5 development	1	4213.0×	0.002	MAFB
abducens nerve formation	1	4213.0×	0.002	MAFB
brain segmentation	1	2808.7×	0.002	MAFB
regulation of myeloid cell differentiation	1	1685.2×	0.003	MAFB
cornified envelope assembly	1	1404.3×	0.003	MAFB
segment specification	1	1053.2×	0.004	MAFB
negative regulation of erythrocyte differentiation	1	766.0×	0.005	MAFB
regulation of axonogenesis	1	443.5×	0.007	CHN1
motor neuron axon guidance	1	351.1×	0.007	CHN1
integrated stress response signaling	1	351.1×	0.007	MAFB
sensory organ development	1	337.0×	0.007	MAFB
respiratory gaseous exchange by respiratory system	1	312.1×	0.007	MAFB
negative regulation of osteoclast differentiation	1	271.8×	0.007	MAFB
T cell differentiation in thymus	1	205.5×	0.009	MAFB
ephrin receptor signaling pathway	1	172.0×	0.010	CHN1
thymus development	1	168.5×	0.010	MAFB
inner ear morphogenesis	1	150.5×	0.010	MAFB
response to nutrient	1	147.8×	0.010	MAFB
keratinocyte differentiation	1	123.9×	0.011	MAFB
fat cell differentiation	1	90.6×	0.015	MAFB
protein processing	1	85.1×	0.015	MAFB
regulation of small GTPase mediated signal transduction	1	72.0×	0.017	CHN1
in utero embryonic development	1	36.0×	0.032	MAFB
regulation of DNA-templated transcription	1	15.8×	0.070	MAFB
positive regulation of DNA-templated transcription	1	14.0×	0.076	MAFB
negative regulation of transcription by RNA polymerase II	1	8.9×	0.114	MAFB
regulation of transcription by RNA polymerase II	1	5.8×	0.164	MAFB

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
CHN1	0	0
MAFB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CHN1, MAFB

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)
CHN1	0	—
MAFB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.