IQSEC3

protein-coding

IQ motif and Sec7 domain ArfGEF 3, the group of IQSEC ArfGEF family

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including activation of GTPase activity; regulation of postsynaptic neurotransmitter receptor internalization; and regulation of small GTPase mediated signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001170738.2

Inheritance

ClinVar variants

U:152B:18

Top phenotype

IQSEC3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr12:66,767-178,455

External References & Databases

Ensembl (ENSG00000120645)

Transcript & Mutation Effects

hg38 • Region Span ~111.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IQSEC3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 148

not providedTotal: 14

IQSEC3-related disorderTotal: 3

Fetal akinesia deformation sequence 1Total: 2

Arthrogryposis multiplex congenitaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001170738.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	9 clinvar		13
missense			147 clinvar	5 clinvar	3 clinvar	155
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	152	14	4	170

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001170738.2	RefSeq	NP_001164209.1	14	MANE Select
ENST00000538872.6	Ensembl	ENSP00000437554.1	14	MANE Select
NM_015232.2	RefSeq	NP_056047.1	11	Standard
ENST00000382841.2	Ensembl	ENSP00000372292.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

actin cytoskeleton organization
regulation of ARF protein signal transduction

Molecular Function

ARF guanyl-nucleotide exchange factor activity

Cellular Component

cytoplasm
postsynaptic density
cell junction
postsynaptic membrane
inhibitory synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000538872
Coding exons: 14
Length: 111696
Individuals with no LoFs: 122177
Homozygous LoFs: 48
Heterozygous LoFs: 3523
Defined: 125748
p: 0.0143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.15	597	682	0.876	0.0000433	7398
Missense (PolyPhen)		186	279.36	0.6658		2908
Synonymous	-0.728	348	331	1.05	0.0000243	2434
Loss of Function	4.33	13	44.0	0.295	0.00000221	494

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0081	0.0081	notable
Latino/Admixed American	0.0067	0.0066	notable
Ashkenazi Jewish	0.0091	0.0092	notable
East Asian	0.00011	0.00011	rare
Finnish	0.032	0.031	notable
European (Non-Finnish)	0.020	0.020	notable
South Asian	0.0049	0.0049	notable
Other	0.016	0.016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) for ARF1. {ECO:0000269|PubMed:17981261}.;

Intolerance Scores

LoFtool: 0.350
RVIS EVS: -0.84
RVIS percentile EVS: 11.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.246

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium