Distal 10q deletion syndrome

Summary

Distal 10q deletion syndrome (MONDO:0012315) is a disease with 6 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 6
• ClinVar variants: 7
• Phenotypes (HPO): 92

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001328	Specific learning disability	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0000219	Thin upper lip vermilion	Frequent (30-79%)
HP:0000356	Abnormality of the outer ear	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000805	Enuresis	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0002280	Enlarged cisterna magna	Frequent (30-79%)
HP:0002395	Lower limb hyperreflexia	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0030084	Clinodactyly	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0000448	Prominent nose	Occasional (5-29%)
HP:0000483	Astigmatism	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0000657	Oculomotor apraxia	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000954	Single transverse palmar crease	Occasional (5-29%)
HP:0001156	Brachydactyly	Occasional (5-29%)
HP:0001182	Tapered finger	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001321	Cerebellar hypoplasia	Occasional (5-29%)
HP:0001349	Facial diplegia	Occasional (5-29%)
HP:0001622	Premature birth	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001763	Pes planus	Occasional (5-29%)
HP:0001852	Sandal gap	Occasional (5-29%)
HP:0002169	Clonus	Occasional (5-29%)
HP:0000076	Vesicoureteral reflux	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000119	Abnormality of the genitourinary system	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	distal 10q deletion syndrome
Mondo ID	MONDO:0012315
MeSH	C567182
OMIM	609625
Orphanet	96148
DOID	DOID:0060390
SNOMED CT	718687003
UMLS	C2674937
MedGen	436306
GARD	0003711
Is cancer (heuristic)	no

Also known as: 10q deletion · 10q monosomy · chromosome 10q deletion · chromosome 10q26 deletion syndrome · deletion 10q · distal deletion 10q · distal monosomy 10q · distal monosomy type 10q · monosomy 10q · monosomy 10qter · partial monosomy 10q · telomeric deletion 10q · terminal chromosome 10q26 deletion syndrome

Data availability: 7 ClinVar variants.

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 chromosome 10 › partial monosomy of the long arm of chromosome 10 › distal 10q deletion syndrome

Related subtypes (2): chromosome 10q23 deletion syndrome, non-distal monosomy 10q

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

7 retrieved; paginated sample, class counts are floors:

7 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2580338	GRCh37/hg19 10q26.13-26.3(chr10:124895517-135440296)x1	ABRAXAS2	Pathogenic	criteria provided, single submitter
625556	GRCh37/hg19 10q25.3-26.13(chr10:117024753-124942806)	FGFR2	Pathogenic	criteria provided, single submitter
2574693	GRCh37/hg19 10q26.13-26.3(chr10:123477898-135427143)	KNDC1	Pathogenic	no assertion criteria provided
4819226	Single allele	LOC130004906	Pathogenic	criteria provided, single submitter
2574686	GRCh37/hg19 10p13-q26.3(chr10:12829206-135427143)	PRXL2A	Pathogenic	no assertion criteria provided
1077185	Single allele	STK32C	Pathogenic	criteria provided, single submitter
2671973	GRCh37/hg19 10q26.2-26.3(chr10:128289206-135427143)x1	TCERG1L	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STK32C	HGNC:21332	ENSG00000165752	Q86UX6	Serine/threonine-protein kinase 32C	clinvar
TCERG1L	HGNC:23533	ENSG00000176769	Q5VWI1	Transcription elongation regulator 1-like protein	clinvar
PRXL2A	HGNC:28651	ENSG00000122378	Q9BRX8	Peroxiredoxin-like 2A	clinvar
ABRAXAS2	HGNC:28975	ENSG00000165660	Q15018	BRISC complex subunit Abraxas 2	clinvar
KNDC1	HGNC:29374	ENSG00000171798	Q76NI1	Kinase non-catalytic C-lobe domain-containing protein 1	clinvar
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRXL2A	Peroxiredoxin-like 2A	Involved in redox regulation of the cell.
ABRAXAS2	BRISC complex subunit Abraxas 2	Component of the BRISC complex, a multiprotein complex that specifically cleaves ‘Lys-63’-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates.
KNDC1	Kinase non-catalytic C-lobe domain-containing protein 1	RAS-Guanine nucleotide exchange factor (GEF) that controls the negative regulation of neuronal dendrite growth by mediating a signaling pathway linking RAS and MAP2.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 2 · 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	3	13.9×	0.003
Scaffold/PPI	1	2.9×	0.451
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STK32C	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TCERG1L	Scaffold/PPI	no		WW_dom, FF_domain, WW_dom_sf
PRXL2A	Other/Unknown	no		PXL2A/B/C
ABRAXAS2	Other/Unknown	no		FAM175, BRISC_Abraxas2, MPN
KNDC1	Kinase	yes		Ras-like_Gua-exchang_fac_N, RASGEF_cat_dom, Kinase-like_dom_sf
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2

Expression context

Cohort genes with no expression data: 0.

5 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
anterior cingulate cortex	1
left testis	1
right testis	1
Brodmann (1909) area 23	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1
corpus epididymis	1
left ventricle myocardium	1
pigmented layer of retina	1
middle temporal gyrus	1
secondary oocyte	1
skeletal muscle tissue of biceps brachii	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STK32C	198	ubiquitous	marker	right testis, left testis, anterior cingulate cortex
TCERG1L	103	broad	yes	right lobe of thyroid gland, Brodmann (1909) area 23, left lobe of thyroid gland
PRXL2A	256	ubiquitous	marker	pigmented layer of retina, corpus epididymis, left ventricle myocardium
ABRAXAS2	288	ubiquitous	marker	secondary oocyte, middle temporal gyrus, skeletal muscle tissue of biceps brachii
KNDC1	190	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABRAXAS2	1,201
TCERG1L	1,113
STK32C	942
KNDC1	811
PRXL2A	742
FGFR2	449

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63
ABRAXAS2	Q15018	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRXL2A	Q9BRX8	88.27
STK32C	Q86UX6	79.95
KNDC1	Q76NI1	61.25
TCERG1L	Q5VWI1	59.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 6 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
Signaling by FGFR2 amplification mutants	1	5710.0×	0.002	FGFR2
Signaling by FGFR2 fusions	1	5710.0×	0.002	FGFR2
FGFR2b ligand binding and activation	1	571.0×	0.009	FGFR2
FGFR2c ligand binding and activation	1	439.2×	0.009	FGFR2
Activated point mutants of FGFR2	1	335.9×	0.009	FGFR2
Phospholipase C-mediated cascade; FGFR2	1	317.2×	0.009	FGFR2
Signaling by FGFR2 IIIa TM	1	300.5×	0.009	FGFR2
PI-3K cascade:FGFR2	1	248.3×	0.009	FGFR2
SHC-mediated cascade:FGFR2	1	237.9×	0.009	FGFR2
FRS-mediated FGFR2 signaling	1	219.6×	0.009	FGFR2
FGFR2 alternative splicing	1	211.5×	0.009	FGFR2
Negative regulation of FGFR2 signaling	1	184.2×	0.010	FGFR2
Metalloprotease DUBs	1	150.3×	0.011	ABRAXAS2
PI3K Cascade	1	135.9×	0.011	FGFR2
Signaling by FGFR2 in disease	1	132.8×	0.011	FGFR2
Constitutive Signaling by Aberrant PI3K in Cancer	1	63.4×	0.021	FGFR2
Deubiquitination	1	62.1×	0.021	ABRAXAS2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.025	FGFR2
PIP3 activates AKT signaling	1	33.4×	0.034	FGFR2
RAF/MAP kinase cascade	1	30.5×	0.036	FGFR2
Post-translational protein modification	1	9.6×	0.106	ABRAXAS2
Metabolism of proteins	1	6.2×	0.155	ABRAXAS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	3370.4×	0.006	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	3370.4×	0.006	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	3370.4×	0.006	FGFR2
lateral sprouting from an epithelium	1	3370.4×	0.006	FGFR2
orbitofrontal cortex development	1	1685.2×	0.006	FGFR2
prostate gland morphogenesis	1	1685.2×	0.006	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	1685.2×	0.006	FGFR2
mammary gland bud formation	1	1685.2×	0.006	FGFR2
branch elongation involved in salivary gland morphogenesis	1	1685.2×	0.006	FGFR2
mesenchymal cell differentiation involved in lung development	1	1685.2×	0.006	FGFR2
regulation of osteoblast proliferation	1	1123.5×	0.007	FGFR2
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1123.5×	0.007	FGFR2
prostate epithelial cord elongation	1	1123.5×	0.007	FGFR2
ventricular zone neuroblast division	1	842.6×	0.007	FGFR2
embryonic organ morphogenesis	1	842.6×	0.007	FGFR2
reproductive structure development	1	842.6×	0.007	FGFR2
regulation of morphogenesis of a branching structure	1	842.6×	0.007	FGFR2
positive regulation of phospholipase activity	1	674.1×	0.007	FGFR2
regulation of smooth muscle cell differentiation	1	674.1×	0.007	FGFR2
branching involved in prostate gland morphogenesis	1	674.1×	0.007	FGFR2
epithelial cell proliferation involved in salivary gland morphogenesis	1	674.1×	0.007	FGFR2
mesenchymal cell proliferation involved in lung development	1	674.1×	0.007	FGFR2
epidermis morphogenesis	1	561.7×	0.008	FGFR2
gland morphogenesis	1	481.5×	0.008	FGFR2
branching morphogenesis of a nerve	1	481.5×	0.008	FGFR2
bud elongation involved in lung branching	1	481.5×	0.008	FGFR2
positive regulation of epithelial cell proliferation involved in lung morphogenesis	1	481.5×	0.008	FGFR2
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	1	481.5×	0.008	FGFR2
cerebellar granule cell differentiation	1	421.3×	0.008	KNDC1
pyramidal neuron development	1	421.3×	0.008	FGFR2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 3

Druggability breadth: 3 of 6 evidence-associated genes (50%) 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
PRXL2A	IBRUTINIB
FGFR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR2	59	4
STK32C	1	3
PRXL2A	1	4
TCERG1L	0	0
ABRAXAS2	0	0
KNDC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IBRUTINIB	4	FGFR2, PRXL2A
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LESTAURTINIB	3	FGFR2, STK32C
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2
FORETINIB	2	FGFR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR2	966	Binding:940, Functional:22, ADMET:4
STK32C	148	Binding:148
PRXL2A	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
STK32C	148
FGFR2	966

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
IBRUTINIB	4	FGFR2, PRXL2A
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LESTAURTINIB	3	FGFR2, STK32C
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2
FORETINIB	2	FGFR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	PRXL2A, FGFR2
B	Phased (≥1) drug, not yet approved	1	STK32C
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	KNDC1
E	Difficult family or no structure, no drug	2	TCERG1L, ABRAXAS2

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)
TCERG1L	0	—
ABRAXAS2	0	—
KNDC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.