21q22.11q22.12 microdeletion syndrome

Summary

21q22.11q22.12 microdeletion syndrome (MONDO:0016845) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 59

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		14	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

59 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000280	Coarse facial features	Frequent (30-79%)
HP:0000414	Bulbous nose	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0001531	Failure to thrive in infancy	Frequent (30-79%)
HP:0001792	Small nail	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0006979	Sleep-wake cycle disturbance	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0011344	Severe global developmental delay	Frequent (30-79%)
HP:0012385	Camptodactyly	Frequent (30-79%)
HP:0030084	Clinodactyly	Frequent (30-79%)
HP:0000179	Thick lower lip vermilion	Occasional (5-29%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000311	Round face	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000403	Recurrent otitis media	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000678	Dental crowding	Occasional (5-29%)
HP:0000752	Hyperactivity	Occasional (5-29%)
HP:0000958	Dry skin	Occasional (5-29%)
HP:0000960	Sacral dimple	Occasional (5-29%)
HP:0001106	Periorbital hyperpigmentation	Occasional (5-29%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002307	Drooling	Occasional (5-29%)
HP:0002465	Poor speech	Occasional (5-29%)
HP:0002557	Hypoplastic nipples	Occasional (5-29%)
HP:0002714	Downturned corners of mouth	Occasional (5-29%)
HP:0002750	Delayed skeletal maturation	Occasional (5-29%)
HP:0003086	Acromesomelia	Occasional (5-29%)
HP:0003763	Bruxism	Occasional (5-29%)
HP:0007874	Almond-shaped palpebral fissure	Occasional (5-29%)
HP:0008404	Nail dystrophy	Occasional (5-29%)
HP:0008551	Microtia	Occasional (5-29%)
HP:0008947	Floppy infant	Occasional (5-29%)
HP:0009226	Short proximal phalanx of the 5th finger	Occasional (5-29%)
HP:0009597	Short proximal phalanx of the 2nd finger	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	21q22.11q22.12 microdeletion syndrome
Mondo ID	MONDO:0016845
Orphanet	261323
UMLS	C5192593
MedGen	1681958
GARD	0020779
Is cancer (heuristic)	no

Also known as: 21q22.11-q22.12 microdeletion syndrome · Del(21)(q22.11q22.12) · monosomy 21q22.11-q22.12 · monosomy 21q22.11q22.12

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal deletion › partial deletion of the long arm of chromosome 21 › 21q22.11q22.12 microdeletion syndrome

Related subtypes (1): DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
872829	GRCh37/hg19 21q22.11-22.12(chr21:33205064-36039022)	CFAP298	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFAP298	Orphanet:244	Primary ciliary dyskinesia

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
CFAP298	HGNC:1301	ENSG00000159079	P57076	Cilia- and flagella-associated protein 298	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFAP298	Cilia- and flagella-associated protein 298	Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly.

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)
CFAP298	Other/Unknown	no		CFAP298

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
left testis	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFAP298	173	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFAP298	596

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFAP298	P57076	86.54

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
regulation of cilium movement	1	4213.0×	5e-04	CFAP298
cilium assembly	1	73.6×	0.014	CFAP298

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
CFAP298	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	CFAP298

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)
CFAP298	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.