IQSEC1

Chr 3AR

IQ motif and Sec7 domain ArfGEF 1

Also known as: ARF-GEP100, ARFGEP100, BRAG2, GEP100, IDDSSBA

NCBI Gene: 9922ENSG00000144711UniProt: Q6DN90OMIM: 610166

IQSEC1 encodes a guanine nucleotide exchange factor for ARF proteins that regulates vesicle formation and AMPA receptor internalization at synapses. Biallelic mutations cause autosomal recessive intellectual developmental disorder with short stature and behavioral abnormalities. This gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.221 OMIM phenotype
Clinical Summary— IQSEC1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 210 VUS of 316 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 5.34
OE 0.10 (0.05–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.28Z-score
OE missense 0.75 (0.70–0.81)
496 obs / 660.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.05–0.22)
0≤0.351.4
Missense OE0.75 (0.70–0.81)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 4 / 40.8Missense obs/exp: 496 / 660.9Syn Z: -0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongIQSEC1-related intellectual disability, developmental delay, and short statureOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4289th %ile
GOF
0.5169th %ile
LOF
0.71top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

316 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS210
Likely Benign52
Benign9
Conflicting1
22
Pathogenic
2
Likely Pathogenic
210
VUS
52
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
21
0
22
Likely Pathogenic
1
1
0
0
2
VUS
2
203
5
0
210
Likely Benign
0
8
3
41
52
Benign
0
4
1
4
9
Conflicting
—1
Total32173045296

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

View in ClinVar →

Protein Context — Lollipop Plot

IQSEC1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients