Sirenomelia

Summary

Sirenomelia (MONDO:0017850) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 1 000 000 (Brazil) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 10

Clinical features

Epidemiology

Prevalence records

19 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.98	Brazil	Validated
Prevalence at birth	1-9 / 100 000	1.04	France	Validated
Prevalence at birth	1-9 / 1 000 000	0.62	Italy	Validated
Prevalence at birth	1-9 / 1 000 000	0.64	Spain	Validated
Prevalence at birth	1-9 / 1 000 000	0.54	Netherlands	Validated
Prevalence at birth	1-9 / 1 000 000	0.7	Finland	Validated
Prevalence at birth	1-9 / 1 000 000	0.31	Slovakia	Validated
Prevalence at birth	1-9 / 1 000 000	0.33	Hungary	Validated
Prevalence at birth	1-9 / 1 000 000	0.74	United States	Validated
Prevalence at birth	1-9 / 100 000	1.6	Canada	Validated
Prevalence at birth	1-9 / 1 000 000	0.83	China	Validated
Prevalence at birth	1-9 / 1 000 000	0.79	Australia	Validated
Prevalence at birth	1-9 / 100 000	2.36	Mexico	Validated
Prevalence at birth	1-9 / 100 000	1.36	Latin America	Validated
Prevalence at birth	1-5 / 10 000	12	Colombia	Validated
Point prevalence	<1 / 1 000 000	0.01	Worldwide	Not yet validated
Prevalence at birth	1-9 / 1 000 000	0.98	Worldwide	Not yet validated
Point prevalence	<1 / 1 000 000	0.009	Europe	Not yet validated
Prevalence at birth	1-9 / 1 000 000	0.71	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0000062	Ambiguous genitalia	Very frequent (80-99%)
HP:0000079	Abnormality of the urinary system	Very frequent (80-99%)
HP:0002023	Anal atresia	Very frequent (80-99%)
HP:0008678	Renal hypoplasia/aplasia	Very frequent (80-99%)
HP:0010305	Absence of the sacrum	Very frequent (80-99%)
HP:0010497	Sirenomelia	Very frequent (80-99%)
HP:0001626	Abnormality of the cardiovascular system	Frequent (30-79%)
HP:0002414	Spina bifida	Frequent (30-79%)
HP:0002575	Tracheoesophageal fistula	Frequent (30-79%)
HP:0006501	Aplasia/Hypoplasia of the radius	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sirenomelia
Mondo ID	MONDO:0017850
Orphanet	3169
ICD-11	473306797
NCIT	C118455
SNOMED CT	67254002
UMLS	C0037205
MedGen	52357
GARD	0007652
MedDRA	10049216
NORD	1720
Is cancer (heuristic)	no

Also known as: Fused legs and feet · mermaid malformation · mermaid syndrome · sirenomelia sequence · Sirenomelus · symmelia

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial caudal dysgenesis › sirenomelia

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 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
812557	NM_001265.6(CDX2):c.940T>C (p.Ter314Arg)	CDX2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
CDX2	HGNC:1806	ENSG00000165556	Q99626	Homeobox protein CDX-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDX2	Homeobox protein CDX-2	Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDX2	Transcription factor	no		HTH_motif, HD, Caudal_activation_dom

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
mucosa of transverse colon	1
rectum	1
transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDX2	64	broad	marker	mucosa of transverse colon, rectum, transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDX2	2,157

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDX2	Q99626	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	1	1142.0×	0.002	CDX2
Incretin synthesis, secretion, and inactivation	1	1038.2×	0.002	CDX2
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	519.1×	0.003	CDX2
Peptide hormone metabolism	1	271.9×	0.005	CDX2
Metabolism of proteins	1	12.4×	0.081	CDX2

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 somitogenesis	1	2808.7×	0.004	CDX2
labyrinthine layer development	1	2106.5×	0.004	CDX2
intestinal epithelial cell differentiation	1	1532.0×	0.004	CDX2
trophectodermal cell differentiation	1	991.3×	0.005	CDX2
anterior/posterior axis specification	1	732.7×	0.005	CDX2
establishment or maintenance of epithelial cell apical/basal polarity	1	581.1×	0.005	CDX2
embryonic pattern specification	1	543.6×	0.005	CDX2
digestive tract development	1	526.6×	0.005	CDX2
blood vessel development	1	374.5×	0.006	CDX2
endosome to lysosome transport	1	337.0×	0.006	CDX2
stem cell differentiation	1	300.9×	0.006	CDX2
positive regulation of cell differentiation	1	267.5×	0.006	CDX2
somatic stem cell population maintenance	1	247.8×	0.006	CDX2
animal organ morphogenesis	1	191.5×	0.007	CDX2
positive regulation of cell population proliferation	1	33.6×	0.038	CDX2
cell differentiation	1	29.1×	0.041	CDX2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.063	CDX2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	CDX2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	CDX2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
CDX2	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	1	CDX2

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)
CDX2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.