ENG

Chr 9AD

endoglin

Also known as: END, HHT1, ORW1

NCBI Gene: 2022ENSG00000106991UniProt: P17813OMIM: 131195

Endoglin is a homodimeric transmembrane glycoprotein of the vascular endothelium that functions as a TGF-beta coreceptor and regulates angiogenesis, vascular endothelial cell migration, and maintenance of normal adult vasculature structure and integrity. Mutations cause hereditary hemorrhagic telangiectasia type 1 (Osler-Rendu-Weber syndrome), a multisystemic vascular dysplasia with autosomal dominant inheritance. This condition primarily affects the vascular system with abnormal blood vessel formation leading to telangiectasias and arteriovenous malformations.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.241 OMIM phenotype
Clinical Summary— ENG
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Gene-Disease Validity (ClinGen)
juvenile polyposis syndrome · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
116 unique Pathogenic / Likely Pathogenic· 160 VUS of 500 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ENG
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.999
Z-score 4.78
OE 0.09 (0.04–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.93Z-score
OE missense 0.87 (0.79–0.95)
338 obs / 389.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.04–0.24)
0≤0.351.4
Missense OE0.87 (0.79–0.95)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 3 / 32.3Missense obs/exp: 338 / 389.9Syn Z: -0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveENG-related hereditary haemorrhagic telangiectasiaLOFAD
DN
0.3693th %ile
GOF
0.3094th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 74% of P/LP variants are LoF · LOEUF 0.24

Literature Evidence

LOFThe patients display common clinical features, including intellectual disability with epilepsy, owing to the presence of STXBP1 within the deletion, nail dysplasia and bone malformations, in particular patellar abnormalities attributed to LMX1B deletion, epistaxis and cutaneous-mucous telangiectasiaPMID:26395556

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90
Likely Pathogenic26
VUS160
Likely Benign204
Benign2
Conflicting8
90
Pathogenic
26
Likely Pathogenic
160
VUS
204
Likely Benign
2
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
67
3
20
0
90
Likely Pathogenic
19
6
1
0
26
VUS
3
131
25
1
160
Likely Benign
0
16
25
163
204
Benign
0
1
1
0
2
Conflicting
—8
Total8915772164490

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ENG · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast CancerDepression

E-Mindfulness Approaches for Living After Breast Cancer

RECRUITING
NCT06748222Phase PHASE3NRG OncologyStarted 2025-06-27
Mindfulness (MAPs) Live OnlineMindfulness (MAPs) Digital AppMeditation Only Control Group
Hereditary Hemorrhagic Telangiectasia

Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia

RECRUITING
NCT04469517University Hospital, EssenStarted 2020-08-10
hypoxic induced factors
Other Disorders of Vestibular Function, BilateralBilateral Vestibular Deficiency (BVD)Gentamicin Ototoxicity

Vestibular Implantation in Older Adults

RECRUITING
NCT05676944Phase NAJohns Hopkins UniversityStarted 2023-04-11
Labyrinth Devices MVI™ Multichannel Vestibular Implant System
Hot FlashesMenopause Surgical

Acupuncture With/Without Self-acupressure for Post-oophorectomy Hot Flashes in BRCA Carriers

NOT YET RECRUITING
NCT05331209Phase NAShaare Zedek Medical CenterStarted 2026-12-01
AcupunctureAcupuncture-Acupressure
Non Small Cell Lung CancerEpidermal Growth Factor Receptor Gene MutationStage III Lung Cancer

Prospective Non-Interventional Study Comparing Osimertinib +/- Chemotherapy for EGFR-Mutated NSCLC Patients

RECRUITING
NCT06538038PrECOG, LLC.Started 2024-09-17
OsimertinibOsimertinib + Chemotherapy
Nasopharyngeal Carriage of Streptococcus Pneumoniae

Pneumococcal Carriage, Serotypes, and Antibiotic Resistance in Malaysian Children: A Multi-Centre Study

RECRUITING
NCT07545876IMU University, MalaysiaStarted 2026-04-09
Heart Defects, CongenitalPulmonary Arterial HypertensionGenetic Testing

Genes Associated With Development of Pulmonary Arterial Hypertension in Patients With Congenital Shunt Lesions

RECRUITING
NCT02691689Phase NAUniversitaire Ziekenhuizen KU LeuvenStarted 2015-11
Genetic testing
Breast Cancer Susceptibility Gene (BRCA1) MutationBRCA2 MutationFear of Cancer Recurrence

Cognitive Behavioral Therapy for Fear of Cancer Recurrence in Women With BRCA1/2 Gene

RECRUITING
NCT06817694Phase NACHU de Quebec-Universite LavalStarted 2026-02
Cognitive-behavioral group therapy
Hereditary Hemorrhagic Telangiectasia

Cardiac Evaluation in Hereditary Hemorrhagic Telangiectasia

NOT YET RECRUITING
NCT07101575Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-08-05
Transthoracic echocardiography
Other Disorders of Vestibular Function, BilateralBilateral Vestibular Deficiency (BVD)Gentamicin Ototoxicity

Vestibular Implantation to Treat Adult-Onset Bilateral Vestibular Hypofunction

RECRUITING
NCT05674786Phase NAJohns Hopkins UniversityStarted 2023-02-28
Labyrinth Devices MVI™ Multichannel Vestibular Implant System
Shwachman-Diamond SyndromeSDSIBMF

Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform

RECRUITING
NCT06999954Shwachman-Diamond Syndrome Alliance IncStarted 2024-02-07
Cancer EducationSpanish Language Cancer Education

Outreach Core Activities

RECRUITING
NCT05832177H. Lee Moffitt Cancer Center and Research InstituteStarted 2023-03-22
Cancer CientoUno (101) programLatinos y el cáncer/Hablemos de cáncer (Translation in English: Latinos and Cancer/Let's Talk About Cancer)¡Salud! Serie de Charlas (Translation in English: Health! Talk Series)
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Charis Eng: an appreciation.
Foulkes WD et al.·J Med Genet
2024
Eng Meng Tan
Chan EKL et al.·Ann Rheum Dis
2024
Evaluation of Types of Vertigo With Electronystagmography: An Experience From a Tertiary Care Hospital in West Bengal, India
Saha S et al.·Cureus
2023
Endoglin in the Spotlight to Treat Cancer
González Muñoz T et al.·Int J Mol Sci
2021
Safety and Benefits of Contraceptives Implants: A Systematic Review
Rocca ML et al.·Pharmaceuticals (Basel)
2021Review
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Generation of ENG p.Met1Val mutant LUMCi029-A-2 for modeling Hereditary Hemorrhagic Telangiectasia type 1.
Cantarini C et al.·Stem Cell Res
2026Functional
Validation of the Charité Alarm Fatigue Questionnaire (CAFQa-Eng) for Use with English-Speaking Critical Care Clinicians.
Ruppel H et al.·Jt Comm J Qual Patient Saf
2026
Targeting a Pathogenic Variant Creating an Upstream AUG in the ENG 5' Untranslated Region with Antisense Oligonucleotides Fails to Restore Protein Expression.
Doisy M et al.·Nucleic Acid Ther
2026
[Clinical phenotype and genetic analysis of a child with Hereditary hemorrhagic telangiectasia combined with growth hormone deficiency due to variant of ENG gene].
Sun M et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
Hereditary Hemorrhagic Telangiectasia Prevalence Estimates Calculated From GnomAD Allele Frequencies of Predicted Pathogenic Variants in ENG and ACVRL1.
Anzell AR et al.·Circ Genom Precis Med
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients