Endocrine system disorder

Summary

Endocrine system disorder (MONDO:0005151) is a disease (an umbrella term covering 48 Mondo subtypes) with 1 cohort gene (11 GWAS associations across 16 studies) and 148 clinical trials. Top therapeutic interventions include levothyroxine, palopegteriparatide, and somatropin.

At a glance

• Umbrella term: 48 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 11
• Clinical trials: 148

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	endocrine system disorder
Mondo ID	MONDO:0005151
EFO	EFO:0001379
MeSH	D004700
DOID	DOID:28
NCIT	C3009
SNOMED CT	362969004
UMLS	C0014130
MedGen	4043
Anatomy (UBERON)	UBERON:0000949
Is cancer (heuristic)	no

Also known as: disease of endocrine system · disease or disorder of endocrine system · disorder of endocrine system · endocrine disease · endocrine disorder · endocrine system disease · endocrine system disease or disorder · endocrine system disorder · endocrinopathy · thyroid or other glandular disorders

Data availability: 11 GWAS associations (16 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 48 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder

Related subtypes (18): disorder of orbital region, integumentary system disorder, musculoskeletal system disorder, urinary system disorder, syndromic disease, auditory system disorder, breast disorder, connective tissue disorder, digestive system disorder, cardiovascular disorder, reproductive system disorder, immune system disorder, nervous system disorder, respiratory system disorder, hematologic disorder, mouth disorder, disorder of visual system, otorhinolaryngologic disease

Subtypes (48): autoimmune disorder of endocrine system, parathyroid gland disorder, endocrine gland neoplasm, gonadal disorder, pancreas disorder, thyroid gland disorder, pituitary gland disorder, thymus gland disorder, liver disorder, adrenal gland disorder, hyperinsulinemic hypoglycemia, non-neoplastic bile duct disorder, endocrine tuberculosis, campomelic dysplasia, polycystic ovary syndrome, dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome, hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome, genito-palato-cardiac syndrome, hypoinsulinemic hypoglycemia and body hemihypertrophy, Bamforth-Lazarus syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, Wolfram-like syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, estrogen resistance syndrome, short stature, microcephaly, and endocrine dysfunction, polyendocrinopathy, pituitary deficiency, hereditary endocrine growth disease, diencephalic syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, neonatal iodine exposure, disorders of vitamin D metabolism, rapid-onset childhood obesity-hypothalamic dysfunction-hypoventilation-autonomic dysregulation syndrome, duplication of the pituitary gland, familial hypocalciuric hypercalcemia, hypothalamic adipsic hypernatraemia syndrome, Leydig cell hypoplasia, inherited obesity, beta thalassemia, thyroid hormone metabolism, abnormal, neuroendocrine disorder, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, parneoplastic endocrine syndrome, 17,20-lyase deficiency, isolated, 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete, 17-alpha-hydroxylase/17,20-lyase deficiency, combined partial, disorder of GNAS inactivation, acquired hypothalamic obesity

Genetics & variants

GWAS landscape

11 GWAS associations across 16 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs180812494	1e-11	SMIM14-DT - UBE2K	C	3.38
rs146557196	1e-11	RPS6P12 - RASEF	T	3.25
rs192373916	2e-11	PIGN	G	3.09
rs199897886	3e-11	RNF151	C	1.91
rs190825105	4e-11	PRSS23, PRSS23-AS1	G	3.14
rs568186039	4e-11	ITCH	C	2.53
chr6:10869415	3e-09		A	0.09
chrX:147885538	6e-09		T	1.32
rs9637800	2e-08	CDH12	?
chr5:78401268	2e-08		G	2.13
chr12:84202885	5e-08		T	1.8

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90038599	Donertas HM	2021	51,949	432,649	Common genetic associations between age-related diseases.
GCST90473185	UK Biobank Whole-Genome Sequencing Consortium	2025	9,621	448,819	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667958	UK Biobank Whole-Genome Sequencing Consortium	2025	9,621	448,819	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90473235	UK Biobank Whole-Genome Sequencing Consortium	2025	3,439	455,001	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90477352	Verma A	2024	1,328	446,581	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651563	Liu TY	2025	1,007	224,577	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90473194	UK Biobank Whole-Genome Sequencing Consortium	2025	403	458,037	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90479908	Verma A	2024	319	120,617	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481602	Verma A	2024	319	120,617	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473186	UK Biobank Whole-Genome Sequencing Consortium	2025	282	9,331	Whole-genome sequencing of 490,640 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	10

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	6
unknown	4

Functional consequences

Consequence	Count
intron_variant	4
unknown	4
intergenic_variant	2
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs180812494	4	39681844	C>G,T	0.001	intergenic_variant	SMIM14-DT - UBE2K	1e-11	Tier 4: intronic/intergenic
rs146557196	9	82947340	T>C	0.001	intron_variant	RPS6P12 - RASEF	1e-11	Tier 4: intronic/intergenic
rs192373916	18	62020678	G>A	0.001	intergenic_variant	PIGN	2e-11	Tier 4: intronic/intergenic
rs199897886	16	1968776	C>T	0.001	missense_variant	RNF151	3e-11	Tier 1: coding
rs190825105	11	86908727	G>A,C	0	intron_variant	PRSS23, PRSS23-AS1	4e-11	Tier 4: intronic/intergenic
rs568186039	20	34488939	C>T	0	intron_variant	ITCH	4e-11	Tier 4: intronic/intergenic
chr6:10869415							3e-09	Tier 4: intronic/intergenic
chrX:147885538							6e-09	Tier 4: intronic/intergenic
rs9637800	5	22522840	C>T	0.05	intron_variant	CDH12	2e-08	Tier 4: intronic/intergenic
chr5:78401268							2e-08	Tier 4: intronic/intergenic
chr12:84202885							5e-08	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
EBF2	Limited	Autosomal dominant	endocrine system disorder

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
EBF2	HGNC:19090	ENSG00000221818	Q9HAK2	Transcription factor COE2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EBF2	Transcription factor COE2	Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation.

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)
EBF2	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold

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
dorsal root ganglion	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EBF2	185	broad	marker	dorsal root ganglion, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EBF2	1,291

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EBF2	Q9HAK2	73.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	380.7×	0.003	EBF2

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
cell fate determination	1	936.2×	0.004	EBF2
brown fat cell differentiation	1	432.1×	0.004	EBF2
adipose tissue development	1	401.2×	0.004	EBF2
positive regulation of cold-induced thermogenesis	1	163.6×	0.008	EBF2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	EBF2

Therapeutics

Drugs indicated for this disease

4 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Hydrocortisone	Approved (phase 4)
Methylprednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Somatropin	Approved (phase 4)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)

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
EBF2	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	EBF2

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)
EBF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 148.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	85
PHASE3	21
PHASE2	19
PHASE1/PHASE2	8
PHASE1	8
PHASE4	5
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01831869	PHASE4	UNKNOWN	Effect of L-Thyroxine on Lipid Profiles and Atherosclerosis in Subclinical Hypothyroidism
NCT01848171	PHASE4	UNKNOWN	Effects of L-thyroxine Replacement on Serum Lipid and Atherosclerosis in Hypothyroidism
NCT04653779	PHASE4	UNKNOWN	A Clinical Trial to Evaluate the Preference Regarding Convenience of Medication and Efficacy/Safety of SUGAMET®XR Tablet 5/1000mg
NCT04700436	PHASE4	COMPLETED	Efficacy and Safety of EzetimiBe/Rosuvastatin in Diabetic Dislipidemia With Hypertriglyceridaemia
NCT05084079	PHASE4	UNKNOWN	Different Initial Insulin Dose Regimens on Time to Achieve Glycemic Targets and Treatment Safety in SIIT
NCT05276063	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
NCT05778071	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism
NCT06112340	PHASE2/PHASE3	RECRUITING	Extension Study of Two Doses of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
NCT07081997	PHASE3	RECRUITING	A Phase 3 Randomized Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism
NCT07613307	PHASE3	NOT_YET_RECRUITING	A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes Who Observe Ramadan Fasting
NCT00163215	PHASE3	COMPLETED	Growth Retardation In Children With Special Pathological Conditions Or Disease
NCT00174187	PHASE3	TERMINATED	Treatment With Recombinant Human Growth Hormone (GH) in Children With Short Stature Secondary to a Long Term Corticoid Therapy
NCT00174291	PHASE3	TERMINATED	Prevention of Growth Retardation by Early Treatment With Growth Hormone (GH) in Children With CJA Treated by Corticosteroid Therapy
NCT00935766	PHASE3	TERMINATED	Effect of Fish Oil (Omega-3 Fatty Acids) on Arteries
NCT01964430	PHASE3	COMPLETED	Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the Apact Study)
NCT02781727	PHASE3	COMPLETED	A Phase 3 Trial of the Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
NCT03305016	PHASE3	COMPLETED	A Safety, Tolerability and Efficacy Study of TransCon hGH in Children With Growth Hormone Deficiency
NCT03344458	PHASE3	COMPLETED	A Long-Term Trial Investigating Safety and Efficacy of TransCon hGH in Children With Growth Hormone Deficiency Who Have Completed a Prior TransCon hGH Clinical Trial
NCT04326374	PHASE3	UNKNOWN	Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Chinese Pediatric Growth Hormone Deficiency
NCT04371978	PHASE3	TERMINATED	Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
NCT04615273	PHASE3	COMPLETED	A Trial to Compare the Efficacy and Safety of Once-weekly Lonapegsomatropin With Placebo and a Daily Somatropin Product in Adults With Growth Hormone Deficiency
NCT04701203	PHASE3	COMPLETED	A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism
NCT04809220	PHASE3	COMPLETED	A Study of Two Doses of Dulaglutide (LY2189265) in Japanese Patients With Type 2 Diabetes
NCT05171855	PHASE3	COMPLETED	A Trial to Investigate Long Term Efficacy and Safety of Lonapegsomatropin in Adults With Growth Hormone Deficiency
NCT05260021	PHASE3	COMPLETED	A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both
NCT05387070	PHASE3	COMPLETED	PaTHway CHINA TRIAL: A Trial to Investigating the Safety, Tolerability and Efficacy of TransCon PTH in Adults With Hypoparathyroidism
NCT05505994	PHASE3	UNKNOWN	The Efficacy and Safety of DWP16001 in Combination With Metformin in T2DM Patients Inadequately Controlled on Metformin
NCT05691712	PHASE3	COMPLETED	A Study of Tirzepatide (LY3298176) in Chinese Participants With Type 2 Diabetes
NCT04460872	PHASE2	RECRUITING	Locomotor Training With Testosterone to Promote Bone and Muscle Health After Spinal Cord Injury
NCT04807166	PHASE2	ACTIVE_NOT_RECRUITING	Anlotinib Combined With Carboplatin/Paclitaxel as First-line Treatment in Patients With Advanced Ovarian Cancer
NCT00001849	PHASE2	COMPLETED	New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome
NCT00672386	PHASE2	COMPLETED	A Study of the Safety and Effectiveness of a R256918 in Patients With Type 2 Diabetes
NCT00947713	PHASE1/PHASE2	COMPLETED	Comparison of Micro-dose Human Chorionic Gonadotropin (hCG) With Human Menopausal Gonadotropin (HMG) in Polycystic Ovary Syndrome
NCT01419535	PHASE1/PHASE2	COMPLETED	Mifepristone Effects on Glucose Intolerance in Obese/Overweight Adults
NCT01727973	PHASE1/PHASE2	COMPLETED	Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves’ Orbitopathy
NCT01735617	PHASE2	COMPLETED	Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH
NCT01778348	PHASE2	COMPLETED	Closing the Loop in Children and Adolescents With Type 1 Diabetes in the Home Setting
NCT02102737	PHASE2	COMPLETED	Comparison of A New Technique of Measure of the Insulin Resistance By Scintigraphy With the Reference Technique
NCT02203682	PHASE2	UNKNOWN	Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy
NCT02248701	PHASE2	TERMINATED	Testosterone Plus Finasteride Treatment After Spinal Cord Injury

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEVOTHYROXINE	4	3
PALOPEGTERIPARATIDE	4	3
SOMATROPIN	4	3
DOXYCYCLINE ANHYDROUS	4	2
LONAPEGSOMATROPIN	4	2
TESTOSTERONE ENANTHATE	4	2
ACETIC ACID	4	1
ACIPIMOX	4	1
DULAGLUTIDE	4	1
EVOGLIPTIN	4	1
FINASTERIDE	4	1
FLUDEOXYGLUCOSE F 18	4	1
FLUORODOPA F 18	4	1
INSULIN LISPRO	4	1
LEVOCARNITINE	4	1
LINAGLIPTIN	4	1
LIOTHYRONINE	4	1
MIFEPRISTONE	4	1
NIRAPARIB	4	1
PRALSETINIB	4	1
PRASTERONE	4	1
TESTOSTERONE UNDECANOATE	4	1
TIRZEPATIDE	4	1
LINSITINIB	3	2
ENAVOGLIFLOZIN	3	1
OMEGA-3 FATTY ACIDS	3	1
ORFORGLIPRON	3	1
PENTETREOTIDE	3	1
AZITHROMYCIN MONOHYDRATE	2	1
ENEBOPARATIDE	2	1