Chromosomal disorder

Summary

Chromosomal disorder (MONDO:0019040) is a disease (an umbrella term covering 18 Mondo subtypes) with 1 cohort gene (1 GWAS associations across 5 studies) and 3 clinical trials. Top therapeutic interventions include melatonin.

At a glance

• Umbrella term: 18 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 1
• ClinVar variants: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosomal disorder
Mondo ID	MONDO:0019040
MeSH	D025063
Orphanet	68335
DOID	DOID:0080014
ICD-10-CM	Q90-Q99
NCIT	C34470
SNOMED CT	409709004
UMLS	C0008626
MedGen	3441
Is cancer (heuristic)	no

Also known as: autosomal chromosome disorder · autosomal chromosome disorders · chromosomal disease · chromosomal disorder · chromosomal disorders · chromosome abnormality disorder · chromosome abnormality disorders · chromosome disorder · chromosome disorder, autosomal · chromosome disorders, autosomal · disorder, chromosomal · disorder, chromosome · disorder, chromosome abnormality · disorders, chromosomal · disorders, chromosome

Data availability: 2 ClinVar variants · 1 GWAS association (5 studies).

Disease family

An umbrella term covering 18 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder

Related subtypes (1): hereditary disease

Subtypes (18): mosaic variegated aneuploidy syndrome, syndrome caused by partial chromosomal deletion, syndrome caused by partial chromosomal duplication, Prader-Willi syndrome, Silver-Russell syndrome, Bloom syndrome, duplication/inversion 15q11, polyploidy, autosomal anomaly, gonosome anomaly, FRAXD syndrome, chromosome inversion disorder, aneuploidy, uniparental disomy, ring chromosome disorder, chromosome Xq13 duplication syndrome, chromosome 1p36 deletion syndrome, proximal, chromosome 16q12 duplication syndrome

Genetics & variants

GWAS landscape

1 GWAS associations across 5 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs78716805	1e-08	IMMP2L - DOCK4	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90482476	Verma A	2024	333	450,772	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482477	Verma A	2024	244	450,971	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436778	Zhou W	2018	189	407,937	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651464	Liu TY	2025	188	236,445	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90436779	Zhou W	2018	99	407,937	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs78716805	7	111674003	G>A,T	0.05	intergenic_variant	IMMP2L - DOCK4	1e-08	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1337703	NM_001291303.3(FAT4):c.9597T>A (p.Asp3199Glu)	FAT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1373516	NM_001291303.3(FAT4):c.13700A>G (p.Tyr4567Cys)	FAT4	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FAT4	Orphanet:2136	Hennekam syndrome
FAT4	Orphanet:314679	Cerebrofacioarticular syndrome

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
FAT4	HGNC:23109	ENSG00000196159	Q6V0I7	Protocadherin Fat 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FAT4	Protocadherin Fat 4	Cadherins are calcium-dependent cell adhesion proteins.

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)
FAT4	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G

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
blood vessel layer	1
calcaneal tendon	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FAT4	231	ubiquitous	marker	calcaneal tendon, cortical plate, blood vessel layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FAT4	1,932

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FAT4	Q6V0I7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
hippo signaling	1	732.7×	0.007	FAT4
cell-cell adhesion mediated by cadherin	1	411.0×	0.007	FAT4
heterophilic cell-cell adhesion	1	337.0×	0.007	FAT4
neurogenesis	1	208.1×	0.007	FAT4
cerebral cortex development	1	205.5×	0.007	FAT4
epithelial cell differentiation	1	175.5×	0.007	FAT4
axonogenesis	1	160.5×	0.007	FAT4
homophilic cell-cell adhesion	1	140.4×	0.007	FAT4

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
FAT4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	FAT4

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)
FAT4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT00064597	Not specified	UNKNOWN	Noninvasive Prenatal Diagnosis: Using Fetal Cells From Maternal Blood
NCT00691574	Not specified	TERMINATED	Melatonin Levels in Smith Magenis Syndrome (SMS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MELATONIN	4	1