RET

Chr 10AD

ret proto-oncogene

Also known as: CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1, PTC, RET-ELE1

This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Hirschsprung disease, protection against}MIM #142623
AD
{Hirschsprung disease, susceptibility to, 1}MIM #142623
AD
Medullary thyroid carcinomaMIM #155240
AD
Multiple endocrine neoplasia IIAMIM #171400
AD
Multiple endocrine neoplasia IIBMIM #162300
AD
PheochromocytomaMIM #171300
AD
UniProtMultiple neoplasia 2B
UniProtMultiple neoplasia 2A

Clinical highlights

Gene-disease validity (ClinGen)
multiple endocrine neoplasia type 2B · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
0.12
LOEUF· LoF intol.
Multiple*
Mechanism· G2P
📖
GeneReview available — RET
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.12LOEUF
pLI 1.000
Z-score 6.37
OE 0.04 (0.010.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
0.96Z-score
OE missense 0.90 (0.840.96)
594 obs / 663.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.04 (0.010.12)
00.351.4
Missense OE?0.90 (0.840.96)
00.61.4
Synonymous OE?1.01
01.21.6
LoF obs/exp: 2 / 51.2Missense obs/exp: 594 / 663.2Syn Z: -0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RET · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING
NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14
SunitinibTemsirolimusTrastuzumab and Pertuzumab
Carcinoma, Non-Small-Cell Lung

MYLUNG Consortium Part 3: Observational Study

RECRUITING
NCT05885698US Oncology ResearchStarted 2023-01-30
Lung Cancer

Survival Outcomes of Lung Cancer

RECRUITING
NCT03647098Hunan Province Tumor HospitalStarted 2018-08-01
Treatment
Non Small Cell Lung CancerRET Gene MutationMET Amplification

The Efficacy and Safety of LMV-12 Combined With Osimertinib in NSCLC

RECRUITING
NCT06109558Phase PHASE1, PHASE2Hunan Province Tumor HospitalStarted 2023-12-31
LMV-12(HE003)
Papillary Thyroid CarcinomaThyroid NeoplasmsRET Proto-Oncogene Mutation

RET-US Study - Ultrasound-Based Prediction of RET Alterations and Lateral-Neck Metastasis in Thyroid Cancer

NOT YET RECRUITING
NCT07042984Fujian Medical UniversityStarted 2025-07-01
AI-Ultrasound RET Prediction
Lung Adenocarcinoma

PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC

NOT YET RECRUITING
NCT07416058Phase PHASE2Guangdong Association of Clinical TrialsStarted 2026-01-31
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
Breast Cancer

Lenvatinib+Letrozole Versus Fulvestrant in Metastatic ER+/HER2- Breast Cancer, Post Progression on Al + CDK4/6 Inhibitor

RECRUITING
NCT05181033Phase PHASE2National University Hospital, SingaporeStarted 2021-12-27
Lenvatinib + LetrozoleFulvestrant
NSCLC (Non-small Cell Lung Cancer)Thyroid CancerSolid Tumor Malignancies

Pralsetinib DDI Study in Patients With Advanced or Metastatic Solid Tumors

RECRUITING
NCT07704658Phase PHASE4Rigel PharmaceuticalsStarted 2026-03-04
PralsetinibCYP3A4, CYP2C8, and CYP2C9 substrates, and hormonal contraceptive
Malignant Solid Neoplasms

Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment

RECRUITING
NCT02029001Phase PHASE2Centre Leon BerardStarted 2014-03
Nilotinib (400 mg BID)Everolimus (10 mg QD)Sorafenib (400 mg BID)
NSCLC (Advanced Non-small Cell Lung Cancer)

QL1706 Combined With Chemotherapy in the Treatment of Immune-mediated NSCLC

RECRUITING
NCT07330596Phase PHASE2Anhui Provincial Cancer HospitalStarted 2025-10-30
QL1706 combined with ChemotherapyChemotherapy
Hip Replacement in Osteoarthritis PatientsOsteoarthritis, Hip

Prehabilitation in Older People Undergoing Total Hip Replacement

NOT YET RECRUITING
NCT07048080Phase NAUniversidad de La FronteraStarted 2026-08-02
(P)rehabilitation Progresive Resistance Exercise TrainingPrehabilitation Group Deuterated WaterUsual Care Group Deuterated Water
Patients Must Have Histologically or Cytologically Confirmed Locally Advanced or Metastatic NSCLCEGFR Mutation-negative and ALK Rearrangement-negativeEastern Cooperative Oncology Group Performance Status (ECOG PS) Score of 0 to 2

Efficacy and Safety of Ivonescimab Monotherapy as First-Line Treatment for PD-L1-Positive, Driver Gene-Negative, Locally Advanced or Metastatic NSCLC: A Multicenter, Prospective, Real-World Cohort Study

RECRUITING
NCT07696832Guangdong Association of Clinical TrialsStarted 2026-01-20
Ivonescimab Injection