IQSEC2

IQ motif and Sec7 domain ArfGEF 2, the group of IQSEC ArfGEF family

Basic information

Region (hg38): X:53225827-53321350

Previous symbols: [ "MRX1", "MRX78", "MRX18" ]

Links

ENSG00000124313 ∙ NCBI:23096 ∙ OMIM:300522 ∙ HGNC:29059 ∙ Uniprot:Q5JU85 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 1 (Definitive), mode of inheritance: XLD
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 1 (Strong), mode of inheritance: XL
• intellectual disability, X-linked 1 (Definitive), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 1	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	7943039; 3177466; 20473311

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IQSEC2 gene.

• Intellectual disability, X-linked 1 (756 variants)
• not provided (311 variants)
• Inborn genetic diseases (104 variants)
• not specified (81 variants)
• See cases (7 variants)
• Intellectual disability (6 variants)
• IQSEC2-related condition (4 variants)
• Tip-toe gait (2 variants)
• Neurodevelopmental disorder (2 variants)
• Seizure (2 variants)
• Abnormal brain morphology (1 variants)
• Neurodevelopmental delay (1 variants)
• Autism spectrum disorder (1 variants)
• Specific learning disability (1 variants)
• Undetermined early-onset epileptic encephalopathy (1 variants)
• Paraplegia-intellectual disability-hyperkeratosis syndrome (1 variants)
• Intellectual developmental disorder, X-linked 108 (1 variants)
• IQSEC2-related X-linked neurodevelopmental disorder (1 variants)
• Specific learning disability;Involuntary movements (1 variants)
• Severe intellectual deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IQSEC2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	10	237	27	275
missense	5	12	314	47	16	394
nonsense	37	9				46
start loss						0
frameshift	69	11	1			81
inframe indel		1	8	1	1	11
splice donor/acceptor (+/-2bp)	7	10				17
splice region		3	11	11	3	28
non coding			5	61	29	95
Total	118	44	338	346	73

Highest pathogenic variant AF is 0.00000907

Variants in IQSEC2

This is a list of pathogenic ClinVar variants found in the IQSEC2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-53227827-C-T			Likely benign (Jun 01, 2023)
X-53234206-C-G		not specified	Likely benign (Mar 18, 2016)
X-53234221-A-T			Uncertain significance (Dec 05, 2019)
X-53234223-A-G			Likely pathogenic (Aug 23, 2019)
X-53234227-C-T		Intellectual disability, X-linked 1	Uncertain significance (Sep 15, 2021)
X-53234228-G-A			Likely benign (Apr 09, 2018)
X-53234229-G-A		Intellectual disability, X-linked 1	Uncertain significance (Feb 04, 2022)
X-53234231-G-A		Intellectual disability, X-linked 1	Likely benign (Oct 26, 2022)
X-53234238-C-T		Intellectual disability, X-linked 1	Uncertain significance (Oct 04, 2023)
X-53234240-G-A		Intellectual disability, X-linked 1	Likely benign (May 15, 2023)
X-53234247-T-TTGGCC		Intellectual disability, X-linked 1	Pathogenic (Jul 31, 2017)
X-53234252-CT-C			Uncertain significance (May 07, 2023)
X-53234256-G-A		Intellectual disability, X-linked 1	Uncertain significance (Aug 17, 2023)
X-53234266-TG-T		Intellectual disability, X-linked 1	Pathogenic (May 04, 2022)
X-53234266-T-TG		Intellectual disability, X-linked 1	Pathogenic (Jun 25, 2023)
X-53234267-G-T		Intellectual disability, X-linked 1	Likely benign (Nov 03, 2023)
X-53234268-G-A		Intellectual disability, X-linked 1	Conflicting classifications of pathogenicity (Jan 01, 2024)
X-53234267-G-GGGGGGGTTGGCTGTGCC		Intellectual disability, X-linked 1	Pathogenic (Jan 23, 2020)
X-53234270-G-A		not specified	Uncertain significance (Aug 12, 2014)
X-53234275-T-TG		Intellectual disability, X-linked 1	Pathogenic (Nov 22, 2022)
X-53234278-C-T		not specified • Intellectual disability, X-linked 1 • Inborn genetic diseases	Benign (Jan 29, 2024)
X-53234279-T-C		Intellectual disability, X-linked 1	Likely benign (Dec 18, 2021)
X-53234295-G-C		Intellectual disability, X-linked 1	Uncertain significance (May 16, 2022)
X-53234296-A-G		Intellectual disability, X-linked 1	Uncertain significance (Aug 23, 2022)
X-53234299-C-T		Intellectual disability, X-linked 1	Uncertain significance (Mar 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IQSEC2	protein_coding	protein_coding	ENST00000396435	15	88465

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000155	124418	0	1	124419	0.00000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.19	241	598	0.403	0.0000515	9587
Missense in Polyphen		48	184.28	0.26047		2482
Synonymous	1.91	210	248	0.845	0.0000204	3186
Loss of Function	5.37	1	35.6	0.0281	0.00000282	577

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000123	0.00000888
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Is a guanine nucleotide exchange factor for the ARF GTP- binding proteins. {ECO:0000269|PubMed:26793055}.
• Pathway: Endocytosis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0922

Intolerance Scores

• loftool: 0.228
• rvis_EVS: -0.52
• rvis_percentile_EVS: 21.2

Haploinsufficiency Scores

• pHI: 0.711
• hipred: Y
• hipred_score: 0.617
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.328

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Iqsec2

Gene ontology

• Biological process: actin cytoskeleton organization;regulation of ARF protein signal transduction;modulation of chemical synaptic transmission;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
• Cellular component: cytoplasm;Schaffer collateral - CA1 synapse
• Molecular function: ARF guanyl-nucleotide exchange factor activity