7p22.1 microduplication syndrome

Summary

7p22.1 microduplication syndrome (MONDO:0017792) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000077	Abnormality of the kidney	Very frequent (80-99%)
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000356	Abnormality of the outer ear	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0000924	Abnormality of the skeletal system	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001627	Abnormal heart morphology	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	7p22.1 microduplication syndrome
Mondo ID	MONDO:0017792
Orphanet	314034
SNOMED CT	764703002
UMLS	C4707093
MedGen	1641886
GARD	0021367
Is cancer (heuristic)	no

Also known as: dup(7)(p22.1) · trisomy 7p22.1

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › 7p22.1 microduplication syndrome

Related subtypes (16): Smith-Magenis syndrome, intellectual disability, Buenos-Aires type, intellectual disability, Wolff type, CK syndrome, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, 9p13 microdeletion syndrome, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, Rubinstein-Taybi syndrome, X-linked syndromic intellectual disability, 9q33.3q34.11 microdeletion syndrome, autosomal recessive syndromic intellectual disability, autosomal dominant syndromic intellectual disability, aplasia cutis-enamel dysplasia syndrome, 2p25.3 microduplication syndrome, dyneinopathy

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1696458	Single allele	AIMP2	Uncertain significance	criteria provided, single submitter
1679759	Single allele	MINK1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
MINK1	HGNC:17565	ENSG00000141503	Q8N4C8	Misshapen-like kinase 1	clinvar
AIMP2	HGNC:20609	ENSG00000106305	Q13155	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MINK1	Misshapen-like kinase 1	Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking.
AIMP2	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2	Required for assembly and stability of the aminoacyl-tRNA synthase complex.

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MINK1	Kinase	yes		Prot_kinase_dom, CNH_dom, Ser/Thr_kinase_AS
AIMP2	Other/Unknown	no		GST_C, AIMP2_LysRS-bd, Glutathione-S-Trfase_C_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
CA1 field of hippocampus	1
lower esophagus mucosa	1
skin of leg	1
oocyte	1
secondary oocyte	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MINK1	292	ubiquitous	marker	CA1 field of hippocampus, lower esophagus mucosa, skin of leg
AIMP2	297	ubiquitous	marker	oocyte, secondary oocyte, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AIMP2	2,867
MINK1	1,829

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AIMP2	Q13155	13

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MINK1	Q8N4C8	64.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Cytosolic tRNA aminoacylation	1	219.6×	0.039	AIMP2
tRNA Aminoacylation	1	142.8×	0.039	AIMP2
Selenoamino acid metabolism	1	98.5×	0.039	AIMP2
Transcriptional and post-translational regulation of MITF-M expression and activity	1	89.2×	0.039	AIMP2
Cellular Senescence	1	68.8×	0.041	MINK1
MITF-M-regulated melanocyte development	1	57.1×	0.041	AIMP2
Oxidative Stress Induced Senescence	1	45.3×	0.044	MINK1
Metabolism of amino acids and derivatives	1	33.8×	0.050	AIMP2
Translation	1	31.0×	0.050	AIMP2
Cellular responses to stress	1	18.4×	0.075	MINK1
Cellular responses to stimuli	1	15.7×	0.080	MINK1
Developmental Biology	1	7.2×	0.156	AIMP2
Metabolism of proteins	1	6.2×	0.165	AIMP2
Metabolism	1	5.8×	0.165	AIMP2

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
type II pneumocyte differentiation	1	1053.2×	0.010	AIMP2
regulation of AMPA receptor activity	1	842.6×	0.010	MINK1
regulation of cell-matrix adhesion	1	648.1×	0.010	MINK1
regulation of cell-cell adhesion	1	601.9×	0.010	MINK1
positive regulation of p38MAPK cascade	1	312.1×	0.015	MINK1
regulation of MAPK cascade	1	227.7×	0.016	MINK1
dendrite morphogenesis	1	216.1×	0.016	MINK1
neuron projection morphogenesis	1	138.1×	0.018	MINK1
JNK cascade	1	135.9×	0.018	MINK1
positive regulation of neuron apoptotic process	1	135.9×	0.018	AIMP2
positive regulation of protein ubiquitination	1	106.7×	0.020	AIMP2
positive regulation of JNK cascade	1	81.8×	0.022	MINK1
regulation of cell migration	1	78.8×	0.022	MINK1
MAPK cascade	1	76.6×	0.022	MINK1
protein autophosphorylation	1	72.6×	0.022	MINK1
protein-containing complex assembly	1	56.9×	0.026	AIMP2
translation	1	51.4×	0.027	AIMP2
brain development	1	39.8×	0.031	MINK1
actin cytoskeleton organization	1	39.6×	0.031	MINK1
chemical synaptic transmission	1	38.6×	0.031	MINK1
protein phosphorylation	1	34.0×	0.033	MINK1
negative regulation of cell population proliferation	1	21.1×	0.050	AIMP2
protein ubiquitination	1	20.7×	0.050	AIMP2
apoptotic process	1	14.3×	0.068	AIMP2

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MINK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MINK1	47	4
AIMP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	MINK1
AXITINIB	4	MINK1
SORAFENIB	4	MINK1
NERATINIB	4	MINK1
VANDETANIB	4	MINK1
BOSUTINIB	4	MINK1
NINTEDANIB	4	MINK1
SUNITINIB	4	MINK1
DASATINIB	4	MINK1
ERLOTINIB	4	MINK1
QUIZARTINIB	4	MINK1
CRIZOTINIB	4	MINK1
MIDOSTAURIN	4	MINK1
GEFITINIB	4	MINK1
LINIFANIB	3	MINK1
ENZASTAURIN	3	MINK1
CANERTINIB	3	MINK1
BRIVANIB	3	MINK1
ALVOCIDIB	3	MINK1
CEDIRANIB	3	MINK1
DOVITINIB	3	MINK1
LESTAURTINIB	3	MINK1
RUBOXISTAURIN	3	MINK1
DORAMAPIMOD	2	MINK1
FORETINIB	2	MINK1
MUBRITINIB	2	MINK1
SU-014813	2	MINK1
REBASTINIB	2	MINK1
PF-03715455	2	MINK1
CENISERTIB	2	MINK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MINK1	338	Binding:335, Toxicity:2, Functional:1
AIMP2	23	Binding:21, ADMET:2

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MINK1	338

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	MINK1
AXITINIB	4	MINK1
SORAFENIB	4	MINK1
NERATINIB	4	MINK1
VANDETANIB	4	MINK1
BOSUTINIB	4	MINK1
NINTEDANIB	4	MINK1
SUNITINIB	4	MINK1
DASATINIB	4	MINK1
ERLOTINIB	4	MINK1
QUIZARTINIB	4	MINK1
CRIZOTINIB	4	MINK1
MIDOSTAURIN	4	MINK1
GEFITINIB	4	MINK1
LINIFANIB	3	MINK1
ENZASTAURIN	3	MINK1
CANERTINIB	3	MINK1
BRIVANIB	3	MINK1
ALVOCIDIB	3	MINK1
CEDIRANIB	3	MINK1
DOVITINIB	3	MINK1
LESTAURTINIB	3	MINK1
RUBOXISTAURIN	3	MINK1
DORAMAPIMOD	2	MINK1
FORETINIB	2	MINK1
MUBRITINIB	2	MINK1
SU-014813	2	MINK1
REBASTINIB	2	MINK1
PF-03715455	2	MINK1
CENISERTIB	2	MINK1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MINK1
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	AIMP2

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)
AIMP2	23	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.