IGFBPL1

Chr 9

insulin like growth factor binding protein like 1

Also known as: IGFBP-RP4, IGFBPRP4, bA113O24.1

The protein binds insulin-like growth factors (IGFs) to regulate their half-life and modulate their growth-promoting effects by altering IGF interactions with cell surface receptors. Mutations cause autosomal recessive intellectual developmental disorder with cardiac arrhythmia. This gene shows minimal constraint against loss-of-function variants (pLI 0.00004), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.64
Clinical SummaryIGFBPL1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 75 VUS of 153 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.64LOEUF
pLI 0.000
Z-score 0.26
OE 0.90 (0.511.64)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.44Z-score
OE missense 0.88 (0.741.05)
87 obs / 99.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.90 (0.511.64)
00.351.4
Missense OE0.88 (0.741.05)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 7 / 7.8Missense obs/exp: 87 / 99.3Syn Z: 0.76
DN
0.6162th %ile
GOF
0.6151th %ile
LOF
0.4529th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

153 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic8
VUS75
Likely Benign3
Benign2
60
Pathogenic
8
Likely Pathogenic
75
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
8
0
8
VUS
0
70
5
0
75
Likely Benign
0
0
1
2
3
Benign
2
0
0
0
2
Total270742148

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

View in ClinVar →

Protein Context — Lollipop Plot

IGFBPL1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC