Thyroid ectopia

Summary

Thyroid ectopia (MONDO:0019854) is a disease with 2 cohort genes.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 26

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	14.3	Europe	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0100028	Ectopic thyroid	Obligate (100%)
HP:0000158	Macroglossia	Very frequent (80-99%)
HP:0000239	Large fontanelles	Very frequent (80-99%)
HP:0000271	Abnormality of the face	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000820	Abnormality of the thyroid gland	Very frequent (80-99%)
HP:0000821	Hypothyroidism	Very frequent (80-99%)
HP:0000952	Jaundice	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001324	Muscle weakness	Very frequent (80-99%)
HP:0001537	Umbilical hernia	Very frequent (80-99%)
HP:0002019	Constipation	Very frequent (80-99%)
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration	Very frequent (80-99%)
HP:0003270	Abdominal distention	Very frequent (80-99%)
HP:0100029	Lingual thyroid	Very frequent (80-99%)
HP:0100786	Hypersomnia	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:6000855	Cold intolerance	Frequent (30-79%)
HP:0000958	Dry skin	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001609	Hoarse voice	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0001618	Dysphonia	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	thyroid ectopia
Mondo ID	MONDO:0019854
Orphanet	95712
ICD-11	458251984
UMLS	C0266283
MedGen	78591
GARD	0016841
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › thyroid gland disorder › inherited thyroid metabolism disease › thyroid hormone resistance syndrome › generalized resistance to thyroid hormone › thyroid ectopia

Related subtypes (5): thyroid hormone resistance, generalized, autosomal dominant, thyroid hormone resistance, generalized, autosomal recessive, athyreosis, thyroid hemiagenesis, thyroid hypoplasia

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/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344806	NM_024735.5(FBXO31):c.1000G>A (p.Asp334Asn)	FBXO31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

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
FBXO31	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
FBXO5	HGNC:13584	ENSG00000112029	Q9UKT4	F-box only protein 5	clinvar
FBXO31	HGNC:16510	ENSG00000103264	Q5XUX0	F-box only protein 31	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBXO5	F-box only protein 5	Regulator of APC activity during mitotic and meiotic cell cycle.
FBXO31	F-box only protein 31	Substrate-recognition component of the SCF(FBXO31) protein ligase complex, which specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress, leading to their degradation by the proteas…

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)
FBXO5	Other/Unknown	no		F-box_dom, ZF_ZBR, FBX5_43
FBXO31	Other/Unknown	no		F-box_dom, F-box-like_dom_sf, FBXO31/39

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
ganglionic eminence	1
secondary oocyte	1
ventricular zone	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBXO5	225	ubiquitous	marker	ventricular zone, ganglionic eminence, secondary oocyte
FBXO31	261	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBXO5	2,844
FBXO31	634

Intra-cohort edges

A	B	Sources
FBXO31	FBXO5	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBXO5	Q9UKT4	3
FBXO31	Q5XUX0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Mitotic Metaphase/Anaphase Transition	1	1903.3×	0.004	FBXO5
Phosphorylation of Emi1	1	713.8×	0.005	FBXO5
G1/S-Specific Transcription	1	178.4×	0.011	FBXO5
Regulation of APC/C activators between G1/S and early anaphase	1	154.3×	0.011	FBXO5
SCF-beta-TrCP mediated degradation of Emi1	1	119.0×	0.012	FBXO5
Neddylation	1	23.7×	0.049	FBXO31
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.053	FBXO31

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
negative regulation of DNA endoreduplication	1	4213.0×	0.002	FBXO5
negative regulation of mitotic metaphase/anaphase transition	1	2106.5×	0.002	FBXO5
negative regulation of ubiquitin-protein transferase activity	1	2106.5×	0.002	FBXO5
positive regulation of mesenchymal stem cell migration	1	2106.5×	0.002	FBXO5
spindle assembly involved in female meiosis I	1	1685.2×	0.002	FBXO5
negative regulation of ubiquitin protein ligase activity	1	1685.2×	0.002	FBXO5
DNA damage response	2	53.5×	0.002	FBXO5, FBXO31
protein ubiquitination	2	41.4×	0.002	FBXO5, FBXO31
positive regulation of biomineral tissue development	1	1404.3×	0.002	FBXO5
negative regulation of meiotic nuclear division	1	1053.2×	0.003	FBXO5
vesicle organization	1	561.7×	0.004	FBXO5
mitotic G1 DNA damage checkpoint signaling	1	526.6×	0.004	FBXO31
microtubule polymerization	1	443.5×	0.005	FBXO5
signal transduction in response to DNA damage	1	401.2×	0.005	FBXO31
anaphase-promoting complex-dependent catabolic process	1	351.1×	0.005	FBXO31
negative regulation of cellular senescence	1	324.1×	0.005	FBXO5
regulation of mitotic nuclear division	1	312.1×	0.005	FBXO5
oocyte maturation	1	300.9×	0.005	FBXO5
positive regulation of G2/M transition of mitotic cell cycle	1	300.9×	0.005	FBXO5
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1	187.2×	0.007	FBXO31
regulation of DNA replication	1	183.2×	0.007	FBXO5
regulation of mitotic cell cycle	1	120.4×	0.010	FBXO5
positive regulation of osteoblast differentiation	1	112.3×	0.010	FBXO5
cellular response to oxidative stress	1	77.3×	0.015	FBXO31
proteasome-mediated ubiquitin-dependent protein catabolic process	1	26.1×	0.041	FBXO31
cell division	1	23.1×	0.044	FBXO5
positive regulation of cell population proliferation	1	16.8×	0.059	FBXO5

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
FBXO5	0	0
FBXO31	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	FBXO5, FBXO31

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)
FBXO5	0	—
FBXO31	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.