Distal trisomy 8q

Summary

Distal trisomy 8q (MONDO:0019882) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	distal trisomy 8q
Mondo ID	MONDO:0019882
Orphanet	96100
SNOMED CT	763277009
UMLS	C4706365
MedGen	1637956
GARD	0019315
Is cancer (heuristic)	no

Also known as: distal duplication 8q · distal trisomy type 8q · telomeric duplication 8q · trisomy 8qter

Data availability: 2 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 duplication › partial duplication of chromosome 8 › partial duplication of the long arm of chromosome 8 › distal trisomy 8q

Related subtypes (2): trisomy 8q, 8q12 microduplication 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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2578018	GRCh37/hg19 8q24.21-24.3(chr8:131138343-143473913)	ADCY8	Pathogenic	no assertion criteria provided
2671975	GRCh37/hg19 8q24.13-24.21(chr8:124534271-129054138)x4	ANXA13	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, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADCY8	HGNC:239	ENSG00000155897	P40145	Adenylate cyclase type 8	clinvar
ANXA13	HGNC:536	ENSG00000104537	P27216	Annexin A13	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADCY8	Adenylate cyclase type 8	Catalyzes the formation of cAMP in response to calcium entry leadings to cAMP signaling activation that affect processes suche as synaptic plasticity and insulin secretion.
ANXA13	Annexin A13	Binds to membranes enriched in phosphatidylserine or phosphatidylglycerol in a calcium-dependent manner.

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)
ADCY8	Other/Unknown	no		A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
ANXA13	Other/Unknown	no		Annexin, ANX13, Annexin_repeat_CS

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
caput epididymis	1
dorsal motor nucleus of vagus nerve	1
lateral nuclear group of thalamus	1
duodenum	1
gall bladder	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADCY8	125	ubiquitous	marker	lateral nuclear group of thalamus, dorsal motor nucleus of vagus nerve, caput epididymis
ANXA13	149	tissue_specific	marker	gall bladder, jejunal mucosa, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADCY8	2,527
ANXA13	685

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANXA13	P27216	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADCY8	P40145	71.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. 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
Adenylate cyclase activating pathway	1	1142.0×	0.008	ADCY8
CREB1 phosphorylation through the activation of Adenylate Cyclase	1	878.5×	0.008	ADCY8
Adenylate cyclase inhibitory pathway	1	761.3×	0.008	ADCY8
PKA activation in glucagon signalling	1	671.8×	0.008	ADCY8
PKA activation	1	634.4×	0.008	ADCY8
Activation of GABAB receptors	1	601.0×	0.008	ADCY8
PKA-mediated phosphorylation of CREB	1	571.0×	0.008	ADCY8
GABA B receptor activation	1	543.8×	0.008	ADCY8
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.008	ADCY8
Leishmania parasite growth and survival	1	393.8×	0.008	ADCY8
Calmodulin induced events	1	380.7×	0.008	ADCY8
CaM pathway	1	380.7×	0.008	ADCY8
Ca-dependent events	1	368.4×	0.008	ADCY8
Aquaporin-mediated transport	1	368.4×	0.008	ADCY8
Glucagon signaling in metabolic regulation	1	346.1×	0.008	ADCY8
G-protein mediated events	1	326.3×	0.008	ADCY8
DAG and IP3 signaling	1	317.2×	0.008	ADCY8
GABA receptor activation	1	317.2×	0.008	ADCY8
Response of endothelial cells to shear stress	1	300.5×	0.008	ADCY8
FCGR3A-mediated IL10 synthesis	1	292.8×	0.008	ADCY8
Opioid Signalling	1	265.6×	0.008	ADCY8
PLC beta mediated events	1	265.6×	0.008	ADCY8
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.008	ADCY8
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.008	ADCY8
Cellular responses to mechanical stimuli	1	259.6×	0.008	ADCY8
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.008	ADCY8
GPER1 signaling	1	248.3×	0.008	ADCY8
G alpha (z) signalling events	1	233.1×	0.008	ADCY8
Regulation of insulin secretion	1	219.6×	0.008	ADCY8
Post NMDA receptor activation events	1	203.9×	0.008	ADCY8

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
activation of protein kinase A activity	1	4213.0×	0.004	ADCY8
cellular response to morphine	1	2106.5×	0.004	ADCY8
negative regulation of Golgi to plasma membrane protein transport	1	1404.3×	0.004	ANXA13
positive regulation of Golgi to plasma membrane protein transport	1	1404.3×	0.004	ANXA13
G protein-coupled opioid receptor signaling pathway	1	1203.7×	0.004	ADCY8
glucose mediated signaling pathway	1	1053.2×	0.004	ADCY8
positive regulation of long-term synaptic depression	1	936.2×	0.004	ADCY8
obsolete positive regulation of CREB transcription factor activity	1	842.6×	0.004	ADCY8
regulation of cellular response to stress	1	842.6×	0.004	ADCY8
positive regulation of synaptic plasticity	1	766.0×	0.004	ADCY8
neuroinflammatory response	1	766.0×	0.004	ADCY8
cAMP biosynthetic process	1	702.2×	0.004	ADCY8
cellular response to forskolin	1	561.7×	0.005	ADCY8
cellular response to glucagon stimulus	1	421.3×	0.006	ADCY8
vascular endothelial cell response to laminar fluid shear stress	1	366.4×	0.006	ADCY8
protein complex oligomerization	1	337.0×	0.006	ADCY8
positive regulation of long-term synaptic potentiation	1	337.0×	0.006	ADCY8
renal water homeostasis	1	255.3×	0.007	ADCY8
long-term memory	1	210.7×	0.008	ADCY8
regulation of cytosolic calcium ion concentration	1	191.5×	0.009	ADCY8
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	187.2×	0.009	ADCY8
cellular response to glucose stimulus	1	133.8×	0.012	ADCY8
positive regulation of insulin secretion	1	127.7×	0.012	ADCY8
learning or memory	1	120.4×	0.012	ADCY8
cellular response to calcium ion	1	100.3×	0.014	ADCY8
memory	1	91.6×	0.014	ADCY8
locomotory behavior	1	89.6×	0.014	ADCY8
glucose homeostasis	1	65.3×	0.019	ADCY8
protein homooligomerization	1	61.1×	0.019	ADCY8
positive regulation of cytosolic calcium ion concentration	1	58.5×	0.019	ADCY8

Therapeutics

Drug target analysis

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

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
ADCY8	1	2
ANXA13	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLFORSIN	2	ADCY8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ADCY8	31	Binding:28, Functional:2, ADMET:1
ANXA13	6	Binding:6

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

1 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)
COLFORSIN	2	ADCY8

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	1	ADCY8
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ANXA13

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)
ANXA13	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.