IGFBP1

Chr 7

insulin like growth factor binding protein 1

Also known as: AFBP, IBP1, IGF-BP25, PP12, hIGFBP-1

NCBI Gene: 3484ENSG00000146678UniProt: P08833

This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients. [provided by RefSeq, Aug 2017]

63
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— IGFBP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 37 VUS of 63 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.19LOEUF
pLI 0.001
Z-score 1.15
OE 0.60 (0.33–1.19)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.25Z-score
OE missense 0.94 (0.81–1.09)
125 obs / 133.2 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.0.60 (0.33–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.81–1.09)
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.1.04
0≤1.21.6
LoF obs/exp: 6 / 9.9Missense obs/exp: 125 / 133.2Syn Z: -0.22

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS37
Likely Benign4
21
Pathogenic
1
Likely Pathogenic
37
VUS
4
Likely 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
34
3
0
37
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total03725163

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

View in ClinVar →

Protein Context — Lollipop Plot

IGFBP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Pathophysiological, Genetic, and Hormonal Changes in Preeclampsia: A Systematic Review of the Molecular Mechanisms.
Chiang YT et al.·Int J Mol Sci
2024Review
Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization.
Zhou M et al.·J Adv Res
2020
Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis.
Shih AJ et al.·BMC Med
2022
Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis.
Delenko J et al.·Reprod Biol Endocrinol
2024
Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women.
Loucks AB et al.·J Clin Endocrinol Metab
2003Clinical trial
[Somatomedins].
Chevenne D·Ann Biol Clin (Paris)
1991Review
Liver-bone crosstalk in non-alcoholic fatty liver disease: Clinical implications and underlying pathophysiology.
Zhao J et al.·Front Endocrinol (Lausanne)
2023Review
Equivalency of Multiple Biomarkers to Clinical Pulmonary Arterial Hypertension Survival Risk Models.
Griffiths M et al.·Chest
2024Functional
HBP1 enhances progesterone receptor activity and IGFBP1 expression driving endometrial decidualization.
Guo Y et al.·Commun Biol
2026
High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients.
Wei SY et al.·Sci Rep
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Endometriosis

Research OutSmarts Endometriosis II Study

ENROLLING BY INVITATION
NCT05601596Northwell HealthStarted 2022-05-27
Analysis of menstrual blood to predict endometriosis
Pre-Eclampsia

At High-risk for Pre-eclampsia After Assisted Reproductive Technology

RECRUITING
NCT05746793CRG UZ BrusselStarted 2023-02-15
endometrium biopsyTransabdominal ultrasoundPeripheral phlebotomy

External Resources

Links to major genomics databases and tools