IQSEC2

Chr XX-linked

IQ motif and Sec7 domain ArfGEF 2

Also known as: BRAG1, IQ-ArfGEF, MRX1, MRX18, MRX78, NEDXSB, XLID1

NCBI Gene: 23096ENSG00000124313UniProt: Q5JU85OMIM: 300522

This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 1MIM #309530
X-linked
Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalitiesMIM #301164
X-linked

Clinical highlights

Gene-disease validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
13
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — IQSEC2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.13LOEUF
pLI 1.000
Z-score 5.37
OE 0.03 (0.01–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
5.19Z-score
OE missense 0.40 (0.36–0.45)
241 obs / 598.2 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.03 (0.01–0.13)
0≤0.351.4
Missense OE?0.40 (0.36–0.45)
0≤0.61.4
Synonymous OE?0.85
0≤1.21.6
LoF obs/exp: 1 / 35.6Missense obs/exp: 241 / 598.2Syn Z: 1.91

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IQSEC2 · protein map & ClinVar variants

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

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