IGFBP3

Chr 7

insulin like growth factor binding protein 3

Also known as: BP-53, IBP-3, IBP3, IGFBP-3

NCBI Gene: 3486ENSG00000146674UniProt: P17936

This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

60
ClinVar variants
22
Pathogenic / LP
0.91
pLI score· haploinsufficient
7
Active trials
Clinical Summary— IGFBP3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 35 VUS of 60 total submissions
💊
Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.39LOEUF
pLI 0.910
Z-score 2.58
OE 0.00 (0.00–0.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.79Z-score
OE missense 0.80 (0.68–0.95)
96 obs / 120.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.68–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 0 / 7.8Missense obs/exp: 96 / 120.3Syn Z: -0.63

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS35
Benign3
21
Pathogenic
1
Likely Pathogenic
35
VUS
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
32
3
0
35
Likely Benign
0
0
0
0
0
Benign
0
1
1
1
3
Total03326160

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

View in ClinVar →

Protein Context — Lollipop Plot

IGFBP3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — IGFBP3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis.
Du Q et al.·Cell Death Dis
2022
IGFALS suppresses hepatocellular carcinoma progression by stabilizing PPAR-γ.
Xu L et al.·Int Immunopharmacol
2024
Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis.
Evans DS et al.·Ann Rheum Dis
2015Meta-analysis
IGFBP3 polymorphisms and risk of cancer: a meta-analysis.
Li L et al.·Mol Biol Rep
2010Meta-analysis
Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma.
Li X et al.·Exp Mol Med
2024
HDAC3 and Snail2 complex promotes melanoma metastasis by epigenetic repression of IGFBP3.
Wu N et al.·Int J Biol Macromol
2025
Genetic secrets of long-term glioblastoma survivors.
Jovčevska I·Bosn J Basic Med Sci
2019Review
Targeting a novel apoptotic pathway in human disease.
D'Addio F et al.·Bioessays
2023
[Overgrowth with and without obesity: clinical and molecular principles].
Argente J et al.·An Pediatr (Barc)
2012Review
Hyper-androgenemia and obesity in early-pubertal girls.
Durá-Travé T et al.·J Endocrinol Invest
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CASC15 Promotes Cholangiocyte Proliferation and Liver Fibrosis by Regulating the HNRNPU-IGFBP3 Axis in Biliary Atresia.
Lu Y et al.·Dig Dis Sci
2026
EPCs-derived exosomal miR-7116-3p alleviate high glucose-induced endothelial cell dysfunction by targeting Orai1-IGFBP3 complexes.
Han S et al.·BMJ Open Diabetes Res Care
2026🔓 Open Access
Cancer-associated fibroblast-derived extracellular vesicles deliver ATP6V1C1 to promote lung adenocarcinoma metastasis via the ID1-IGFBP3 axis.
Chen X et al.·Cell Rep
2026
Erratum: IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.
Zhang X et al.·iScience
2026🔓 Open Access
Single-cell transcriptome reveals that immune cells inhibit the repairment of IGFBP3 + stromal cells in thin endometrium.
Zou H et al.·Immunobiology
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Prostate Cancer

GU-01: Glycyrrhizin in Prostate Cancer

RECRUITING
NCT06378346Phase PHASE2University of Illinois at ChicagoStarted 2024-07-25
ObservationGlycyrrhizin - 75 mgGlycyrrhizin - 150 mg
Carcinoma, Intraductal, NoninfiltratingRecurrence, Local NeoplasmBreast Neoplasms

Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

ACTIVE NOT RECRUITING
NCT01357772Phase PHASE3Andrea DeCensiStarted 2008-11-12
Tamoxifenplacebo
Gut MicrobiomeLinear Growth

Effects of Complementary Feeding on Infant Growth and Gut Health

ACTIVE NOT RECRUITING
NCT05012930Phase NAUniversity of Colorado, DenverStarted 2021-08-01
Baby Foods - MeatBaby Foods - DairyBaby Foods - Plant
Breast Carcinoma

Breast Cancer WEight Loss Study (BWEL Study)

ACTIVE NOT RECRUITING
NCT02750826Phase PHASE3Alliance for Clinical Trials in OncologyStarted 2016-09-16
Health Education ProgramWeight Loss Intervention
Gonad Regulating Hormone Adverse ReactionAnalgesic Adverse ReactionDevelopmental Disability

Neurobehavioral Development in Toddlers and Preschoolers in Relation to Prenatal Exposure of Mild Analgesics (NeuroToP - a COPANA Follow up)

ENROLLING BY INVITATION
NCT07316387Rigshospitalet, DenmarkStarted 2024-05-27
IGF1 Deficiency

Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).

RECRUITING
NCT00903110Esteve Pharmaceuticals, S.A.Started 2008-12-09
Increlex®
Pediatric CancerLeukemiaNeoplasms

Integrative Neuromuscular Training in Adolescents and Children Treated for Cancer

ACTIVE NOT RECRUITING
NCT04706676Phase NARigshospitalet, DenmarkStarted 2021-01-26
Integrative neuromuscular training (INT)Active control group: home-based training programmotivational counseling session

External Resources

Links to major genomics databases and tools