IGFBP4

Chr 17

insulin like growth factor binding protein 4

Also known as: BP-4, HT29-IGFBP, IBP4, IGFBP-4

The protein binds insulin-like growth factors I and II, prolonging their half-life and modulating their interaction with cell surface receptors to regulate growth-promoting effects. Mutations cause autosomal dominant short stature with accelerated skeletal maturation, affecting growth and bone development in childhood. The gene shows low constraint to loss-of-function variants, suggesting tolerance to reduced protein levels.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.98
Clinical SummaryIGFBP4
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 31 VUS of 48 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.023
Z-score 1.62
OE 0.43 (0.210.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.85Z-score
OE missense 0.80 (0.690.93)
117 obs / 146.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.210.98)
00.351.4
Missense OE0.80 (0.690.93)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 4 / 9.3Missense obs/exp: 117 / 146.0Syn Z: 1.38

ClinVar Variant Classifications

48 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS31
Likely Benign3
Benign1
8
Pathogenic
1
Likely Pathogenic
31
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
1
0
0
1
VUS
0
30
1
0
31
Likely Benign
0
1
1
1
3
Benign
0
0
0
1
1
Total03210244

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

View in ClinVar →

Protein Context — Lollipop Plot

IGFBP4 · 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

No active trials found for this gene.

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Clinical Literature
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