Duane syndrome type 1

Summary

Duane syndrome type 1 (MONDO:0024265) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Duane syndrome type 1
Mondo ID	MONDO:0024265
OMIM	126800
DOID	DOID:0061027
SNOMED CT	128082002
UMLS	C0994516
MedGen	201329
GARD	0010763
Is cancer (heuristic)	no

Also known as: Duane retraction syndrome 1 · DURS1

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Duane retraction syndrome › Duane syndrome type 1

Related subtypes (3): Duane retraction syndrome 2, Duane retraction syndrome 3 with or without deafness, 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

6 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
3061841	GRCh38/hg38 10q26.2-26.3(chr10:125976998-133427130)x1	ADGRA1	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
585049	NM_001822.7(CHN1):c.1322T>C (p.Ile441Thr)	CHN1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADGRA1	HGNC:13838	ENSG00000197177	Q86SQ6	Adhesion G protein-coupled receptor A1	clinvar
CHN1	HGNC:1943	ENSG00000128656	P15882	N-chimaerin	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)
ADGRA1	Adhesion G protein-coupled receptor A1	Orphan receptor.
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: 1 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.33

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
GPCR	1	8.0×	0.246
Scaffold/PPI	1	5.8×	0.246
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADGRA1	GPCR	yes		GPCR_2_secretin-like, GPCR_2-like_7TM, GPCR_2_secretin-like_CS
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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 9	1
anterior cingulate cortex	1
right frontal lobe	1
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
ADGRA1	94	tissue_specific	yes	right frontal lobe, Brodmann (1909) area 9, anterior cingulate cortex
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
ADGRA1	944

Structural data

PDB: 1 · AlphaFold-only: 2 · 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
ADGRA1	Q86SQ6	64.30
MAFB	Q9Y5Q3	63.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 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 3 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	5617.3×	0.004	MAFB
rhombomere 5 development	1	2808.7×	0.004	MAFB
abducens nerve formation	1	2808.7×	0.004	MAFB
brain segmentation	1	1872.4×	0.004	MAFB
regulation of myeloid cell differentiation	1	1123.5×	0.006	MAFB
cornified envelope assembly	1	936.2×	0.006	MAFB
segment specification	1	702.2×	0.006	MAFB
negative regulation of erythrocyte differentiation	1	510.7×	0.008	MAFB
regulation of axonogenesis	1	295.6×	0.011	CHN1
motor neuron axon guidance	1	234.1×	0.011	CHN1
integrated stress response signaling	1	234.1×	0.011	MAFB
sensory organ development	1	224.7×	0.011	MAFB
respiratory gaseous exchange by respiratory system	1	208.1×	0.011	MAFB
negative regulation of osteoclast differentiation	1	181.2×	0.012	MAFB
T cell differentiation in thymus	1	137.0×	0.015	MAFB
ephrin receptor signaling pathway	1	114.6×	0.016	CHN1
thymus development	1	112.3×	0.016	MAFB
inner ear morphogenesis	1	100.3×	0.017	MAFB
response to nutrient	1	98.5×	0.017	MAFB
keratinocyte differentiation	1	82.6×	0.019	MAFB
fat cell differentiation	1	60.4×	0.024	MAFB
protein processing	1	56.7×	0.025	MAFB
regulation of small GTPase mediated signal transduction	1	48.0×	0.028	CHN1
in utero embryonic development	1	24.0×	0.053	MAFB
cell surface receptor signaling pathway	1	21.4×	0.057	ADGRA1
G protein-coupled receptor signaling pathway	1	12.1×	0.096	ADGRA1
regulation of DNA-templated transcription	1	10.5×	0.106	MAFB
positive regulation of DNA-templated transcription	1	9.3×	0.115	MAFB
negative regulation of transcription by RNA polymerase II	1	5.9×	0.171	MAFB
signal transduction	1	5.3×	0.181	ADGRA1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADGRA1	0	0
CHN1	0	0
MAFB	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
ADGRA1	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	ADGRA1
E	Difficult family or no structure, no drug	2	CHN1, MAFB

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ADGRA1	2	—
CHN1	0	—
MAFB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.