Monosomy 21

Summary

Monosomy 21 (MONDO:0018930) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 3
• Phenotypes (HPO): 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0001531	Failure to thrive in infancy	Very frequent (80-99%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000294	Low anterior hairline	Frequent (30-79%)
HP:0000308	Microretrognathia	Frequent (30-79%)
HP:0000341	Narrow forehead	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001631	Atrial septal defect	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0005484	Secondary microcephaly	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001273	Abnormal corpus callosum morphology	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002623	Overriding aorta	Occasional (5-29%)
HP:0002714	Downturned corners of mouth	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	monosomy 21
Mondo ID	MONDO:0018930
MeSH	C537108
Orphanet	574
NCIT	C36469
UMLS	C0795875
MedGen	162883
GARD	0010860
Is cancer (heuristic)	no

Also known as: 21q deletion · 21q deletion syndrome · 21q monosomy · 21q- syndrome · chromosome 21q deletion · deletion 21q · monosomy 21q · monosomy type 21 · partial 21q monosomy · partial monosomy 21q

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › autosomal anomaly › chromosome 21 disorder › monosomy 21

Related subtypes (5): Down syndrome, ring chromosome 21, tetrasomy 21, maternal uniparental disomy of chromosome 21, paternal uniparental disomy of chromosome 21

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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
236547	GRCh38/hg38 21q21.1-22.11(chr21:21754822-32380347)	KRTAP13-3	Pathogenic	no assertion criteria provided
236548	GRCh38/hg38 21p11.2-q21.3(chr21:13048294-27532614)	LINC01687	Pathogenic	no assertion criteria provided
236549	GRCh38/hg38 21q11.2-21.3(chr21:14000146-27785985)	LOC105377134	Pathogenic	no assertion criteria provided

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, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KRTAP13-3	HGNC:18925	ENSG00000240432	Q3SY46	Keratin-associated protein 13-3	clinvar
LINC01687	HGNC:52474	ENSG00000233215		long intergenic non-protein coding RNA 1687	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRTAP13-3	Keratin-associated protein 13-3	In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through t…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KRTAP13-3	Other/Unknown	no		KRTAP_PMG
LINC01687	Other/Unknown	no

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)	1
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
primordial germ cell in gonad	1
ventricular zone	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1
transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRTAP13-3	3		yes	primordial germ cell in gonad, colonic epithelium, ventricular zone
LINC01687	73	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, transverse colon, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRTAP13-3	508
LINC01687	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRTAP13-3	Q3SY46	44.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Keratinization	1	55.7×	0.036	KRTAP13-3
Developmental Biology	1	14.5×	0.069	KRTAP13-3

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
KRTAP13-3	0	0
LINC01687	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	2	KRTAP13-3, LINC01687

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)
KRTAP13-3	0	—
LINC01687	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.