AXIN2-related attenuated familial adenomatous polyposis

Summary

AXIN2-related attenuated familial adenomatous polyposis (MONDO:0018426) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 11
• Phenotypes (HPO): 7

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)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0005227	Adenomatous colonic polyposis	Frequent (30-79%)
HP:0200063	Colorectal polyposis	Frequent (30-79%)
HP:0003003	Colon cancer	Occasional (5-29%)
HP:0100743	Neoplasm of the rectum	Occasional (5-29%)
HP:0000968	Ectodermal dysplasia	Excluded (0%)
HP:0008070	Sparse hair	Excluded (0%)
HP:3000050	Abnormality of odontoid tissue	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	AXIN2-related attenuated familial adenomatous polyposis
Mondo ID	MONDO:0018426
Orphanet	401911
UMLS	C5680012
MedGen	1826067
GARD	0021703
Is cancer (heuristic)	no

Also known as: AXIN2-related AFAP · AXIN2-related attenuated familial polyposis coli · AXIN2-related attenuated FAP

Data availability: 11 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › intestinal polyposis syndrome › classic or attenuated familial adenomatous polyposis › AXIN2-related attenuated familial adenomatous polyposis

Related subtypes (7): familial adenomatous polyposis 2, familial adenomatous polyposis 3, attenuated familial adenomatous polyposis, Polymerase proofreading-related adenomatous polyposis, classic familial adenomatous polyposis, familial adenomatous polyposis 1, familial adenomatous polyposis 4

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

11 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 4 pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027572	NM_004655.4(AXIN2):c.1928_1941del (p.Ala643fs)	AXIN2	Pathogenic	criteria provided, single submitter
1027574	NM_004655.4(AXIN2):c.2062_2063del (p.Leu688fs)	AXIN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027575	NM_004655.4(AXIN2):c.2086C>T (p.Gln696Ter)	AXIN2	Pathogenic	criteria provided, single submitter
1027576	NM_004655.4(AXIN2):c.2092G>T (p.Glu698Ter)	AXIN2	Pathogenic	criteria provided, single submitter
40260	NM_004655.4(AXIN2):c.1989G>A (p.Trp663Ter)	AXIN2	Pathogenic	criteria provided, multiple submitters, no conflicts
1027569	NM_004655.4(AXIN2):c.204_214del (p.Ala69fs)	AXIN2	Likely pathogenic	criteria provided, single submitter
1027570	NM_004655.4(AXIN2):c.1479_1497dup (p.Leu500fs)	AXIN2	Likely pathogenic	criteria provided, single submitter
1027571	NM_004655.4(AXIN2):c.1647T>G (p.Tyr549Ter)	AXIN2	Likely pathogenic	criteria provided, single submitter
1027573	NM_004655.4(AXIN2):c.2041C>T (p.Gln681Ter)	AXIN2	Likely pathogenic	criteria provided, single submitter
239971	NM_004655.4(AXIN2):c.-12_8del (p.Met1fs)	AXIN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464525	NM_004655.4(AXIN2):c.1201-2A>G	AXIN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
AXIN2	Orphanet:401911	AXIN2-related polyposis

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
AXIN2	HGNC:904	ENSG00000168646	Q9Y2T1	Axin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AXIN2	Axin-2	Inhibitor of the Wnt signaling pathway.

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)
AXIN2	Other/Unknown	no		DIX, Axin_b-cat-bd, RGS

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
body of uterus	1
oviduct epithelium	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AXIN2	221	ubiquitous	marker	oviduct epithelium, upper arm skin, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AXIN2	3,049

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AXIN2	Q9Y2T1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 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
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	1142.0×	0.009	AXIN2
Repression of WNT target genes	1	713.8×	0.009	AXIN2
Degradation of AXIN	1	248.3×	0.013	AXIN2
Ca2+ pathway	1	178.4×	0.013	AXIN2
CHD6, CHD7, CHD8, CHD9 subfamily	1	148.3×	0.013	AXIN2
Deubiquitination	1	124.1×	0.013	AXIN2
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.013	AXIN2
TCF dependent signaling in response to WNT	1	117.7×	0.013	AXIN2
Signaling by WNT	1	112.0×	0.013	AXIN2
Ub-specific processing proteases	1	53.1×	0.024	AXIN2
Post-translational protein modification	1	19.2×	0.062	AXIN2
Metabolism of proteins	1	12.4×	0.088	AXIN2
Signal Transduction	1	10.2×	0.098	AXIN2

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 mismatch repair	1	16852.0×	9e-04	AXIN2
regulation of chondrocyte development	1	16852.0×	9e-04	AXIN2
regulation of centromeric sister chromatid cohesion	1	5617.3×	0.002	AXIN2
maintenance of DNA repeat elements	1	3370.4×	0.002	AXIN2
intramembranous ossification	1	2808.7×	0.002	AXIN2
chondrocyte differentiation involved in endochondral bone morphogenesis	1	2808.7×	0.002	AXIN2
regulation of extracellular matrix organization	1	1872.4×	0.002	AXIN2
mitral valve morphogenesis	1	1685.2×	0.002	AXIN2
secondary heart field specification	1	1532.0×	0.002	AXIN2
dorsal/ventral axis specification	1	1532.0×	0.002	AXIN2
negative regulation of osteoblast proliferation	1	1532.0×	0.002	AXIN2
osteoblast proliferation	1	1404.3×	0.002	AXIN2
cell development	1	887.0×	0.003	AXIN2
cellular response to dexamethasone stimulus	1	581.1×	0.004	AXIN2
odontogenesis	1	526.6×	0.004	AXIN2
aortic valve morphogenesis	1	432.1×	0.004	AXIN2
somitogenesis	1	374.5×	0.004	AXIN2
mRNA stabilization	1	366.4×	0.004	AXIN2
positive regulation of epithelial to mesenchymal transition	1	318.0×	0.004	AXIN2
stem cell proliferation	1	312.1×	0.004	AXIN2
positive regulation of fat cell differentiation	1	300.9×	0.004	AXIN2
negative regulation of osteoblast differentiation	1	295.6×	0.004	AXIN2
bone mineralization	1	271.8×	0.005	AXIN2
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	1	210.7×	0.006	AXIN2
canonical Wnt signaling pathway	1	153.2×	0.008	AXIN2
osteoblast differentiation	1	121.2×	0.009	AXIN2
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.009	AXIN2
intracellular protein localization	1	104.7×	0.010	AXIN2
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.019	AXIN2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
AXIN2	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
AXIN2	14	Binding:14

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	AXIN2

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)
AXIN2	14	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.