IQSEC2

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

Basic information

Region (hg38): X:53225828-53321350

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

• 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
• complex neurodevelopmental disorder (Definitive), mode of inheritance: XL
• intellectual disability, X-linked 1 (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 (1005 variants)
• not_provided (399 variants)
• Inborn_genetic_diseases (137 variants)
• not_specified (91 variants)
• IQSEC2-related_disorder (38 variants)
• Intellectual_disability (8 variants)
• See_cases (7 variants)
• Neurodevelopmental_disorder (2 variants)
• Specific_learning_disability (2 variants)
• Tip-toe_gait (2 variants)
• Severe_intellectual_deficiency (2 variants)
• Seizure (2 variants)
• Undetermined_early-onset_epileptic_encephalopathy (1 variants)
• IQSEC2-related_X-linked_neurodevelopmental_disorder (1 variants)
• Paraplegia-intellectual_disability-hyperkeratosis_syndrome (1 variants)
• Autism_spectrum_disorder (1 variants)
• Neurodevelopmental_delay (1 variants)
• Microcephaly (1 variants)
• Abnormal_brain_morphology (1 variants)
• Intellectual_developmental_disorder,_X-linked_108 (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Autism (1 variants)
• Involuntary_movements (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. These statistics are base on transcript: NM_001111125.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	2	8	322	30	363
missense	11	23	454	103	19	610
nonsense	42	13				55
start loss						0
frameshift	79	20	2			101
splice donor/acceptor (+/-2bp)	9	14	2			25
Total	142	72	466	425	49

Highest pathogenic variant AF is 0.0000265106

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