Chromosome 6q24-q25 deletion syndrome

Summary

Chromosome 6q24-q25 deletion syndrome (MONDO:0013025) is a disease caused by TAB2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TAB2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000377	Abnormal pinna morphology	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000504	Abnormality of vision	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001357	Plagiocephaly	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0012639	Abnormal nervous system morphology	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001319	Neonatal hypotonia	Occasional (5-29%)
HP:0001838	Rocker bottom foot	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0003241	External genital hypoplasia	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)
HP:0100490	Camptodactyly of finger	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 6q24-q25 deletion syndrome
Mondo ID	MONDO:0013025
OMIM	612863
Orphanet	251056
DOID	DOID:0060424
NCIT	C36470
SNOMED CT	719663005
UMLS	C3150215
MedGen	461565
GARD	0003764
Is cancer (heuristic)	no

Also known as: chromosome 6q24-q25 deletion syndrome · chromosome 6q25 microdeletion syndrome · chromosome 6q25-q25 deletion syndrome · Del(6)(q25) · deletion 6q25

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

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 6 › partial deletion of the long arm of chromosome 6 › chromosome 6q24-q25 deletion syndrome

Related subtypes (4): chromosome 6q11-q14 deletion syndrome, 6q16 deletion syndrome, 6q terminal deletion syndrome, 6q25.1 microdeletion syndrome

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
2663766	NC_000006.12:g.(?150381239)(159553952_?)del	AKAP12	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TAB2	Definitive	Autosomal dominant	chromosome 6q24-q25 deletion syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAB2	Orphanet:664401	Cardiac anomalies-short stature-joint hypermobility-facial dysmorphism syndrome due to TAB2 mutation
TAB2	Orphanet:664404	6q25.1 microdeletion syndrome

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
TAB2	HGNC:17075	ENSG00000055208	Q9NYJ8	TGF-beta-activated kinase 1 and MAP3K7-binding protein 2	gencc
AKAP12	HGNC:370	ENSG00000131016	Q02952	A-kinase anchor protein 12	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAB2	TGF-beta-activated kinase 1 and MAP3K7-binding protein 2	Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of ‘Lys-63’-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF).
AKAP12	A-kinase anchor protein 12	Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAB2	Transcription factor	no		Znf_RanBP2, CUE, Znf_RanBP2_sf
AKAP12	Other/Unknown	no		AKAP_WSK, RII-bd_1, AKAP12

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
colonic epithelium	1
parotid gland	1
ventricular zone	1
dorsal root ganglion	1
lateral nuclear group of thalamus	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAB2	293	ubiquitous	marker	parotid gland, ventricular zone, colonic epithelium
AKAP12	287	ubiquitous	marker	pons, lateral nuclear group of thalamus, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAB2	2,606
AKAP12	1,810

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAB2	Q9NYJ8	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AKAP12	Q02952	40.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 60. 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
IRAK2 mediated activation of TAK1 complex	1	571.0×	0.020	TAB2
TICAM1,TRAF6-dependent induction of TAK1 complex	1	519.1×	0.020	TAB2
Alpha-protein kinase 1 signaling pathway	1	519.1×	0.020	TAB2
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	1	380.7×	0.020	TAB2
TRAF6-mediated induction of TAK1 complex within TLR4 complex	1	356.9×	0.020	TAB2
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	1	259.6×	0.020	TAB2
TCR signaling	1	248.3×	0.020	TAB2
activated TAK1 mediates p38 MAPK activation	1	248.3×	0.020	TAB2
TNF signaling	1	211.5×	0.020	TAB2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	178.4×	0.020	TAB2
Nuclear signaling by ERBB4	1	173.0×	0.020	TAB2
TNFR1-induced NF-kappa-B signaling pathway	1	167.9×	0.020	TAB2
NOD1/2 Signaling Pathway	1	158.6×	0.020	TAB2
MAP kinase activation	1	154.3×	0.020	TAB2
TAK1-dependent IKK and NF-kappa-B activation	1	150.3×	0.020	TAB2
Signaling by ERBB4	1	135.9×	0.020	TAB2
Fc epsilon receptor (FCERI) signaling	1	135.9×	0.020	TAB2
Interleukin-1 family signaling	1	135.9×	0.020	TAB2
RHOF GTPase cycle	1	129.8×	0.020	AKAP12
Interleukin-17 signaling	1	126.9×	0.020	TAB2
C-type lectin receptors (CLRs)	1	119.0×	0.020	TAB2
Toll Like Receptor 10 (TLR10) Cascade	1	107.7×	0.020	TAB2
Toll Like Receptor 5 (TLR5) Cascade	1	107.7×	0.020	TAB2
RHOD GTPase cycle	1	102.0×	0.020	AKAP12
MyD88 cascade initiated on plasma membrane	1	102.0×	0.020	TAB2
Toll Like Receptor 3 (TLR3) Cascade	1	96.8×	0.020	TAB2
TRIF (TICAM1)-mediated TLR4 signaling	1	95.2×	0.020	TAB2
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	95.2×	0.020	TAB2
MyD88 dependent cascade initiated on endosome	1	95.2×	0.020	TAB2
MyD88-independent TLR4 cascade	1	92.1×	0.020	TAB2

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
regulation of protein kinase C signaling	1	8426.0×	0.001	AKAP12
positive regulation of hepatic stellate cell migration	1	4213.0×	0.001	AKAP12
positive regulation of oligodendrocyte apoptotic process	1	4213.0×	0.001	AKAP12
obsolete positive regulation of protein kinase A signaling	1	2808.7×	0.001	AKAP12
hepatic stellate cell activation	1	2808.7×	0.001	AKAP12
response to lipopolysaccharide	2	124.8×	0.001	TAB2, AKAP12
obsolete regulation of protein kinase A signaling	1	2106.5×	0.002	AKAP12
negative regulation of vascular permeability	1	561.7×	0.005	AKAP12
non-canonical NF-kappaB signal transduction	1	421.3×	0.006	TAB2
positive regulation of protein kinase activity	1	337.0×	0.007	TAB2
response to electrical stimulus	1	324.1×	0.007	AKAP12
cellular response to interleukin-1	1	140.4×	0.014	AKAP12
negative regulation of autophagy	1	129.6×	0.014	TAB2
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	109.4×	0.016	AKAP12
modulation of chemical synaptic transmission	1	91.6×	0.017	AKAP12
cellular response to tumor necrosis factor	1	81.8×	0.018	AKAP12
positive regulation of tumor necrosis factor production	1	76.6×	0.018	AKAP12
defense response to bacterium	1	54.0×	0.025	TAB2
positive regulation of ERK1 and ERK2 cascade	1	42.6×	0.030	AKAP12
heart development	1	39.4×	0.030	TAB2
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.031	TAB2
inflammatory response	1	18.9×	0.057	TAB2
G protein-coupled receptor signaling pathway	1	18.1×	0.057	AKAP12
signal transduction	1	8.0×	0.121	AKAP12

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAB2	0	0
AKAP12	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TAB2	1	Binding:1
AKAP12	1	Binding:1

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

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	TAB2, AKAP12

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)
TAB2	1	—
AKAP12	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.