IQSEC1

IQ motif and Sec7 domain ArfGEF 1, the group of IQSEC ArfGEF family

Basic information

Region (hg38): 3:12897042-13283281

Links

ENSG00000144711 ∙ NCBI:9922 ∙ OMIM:610166 ∙ HGNC:29112 ∙ Uniprot:Q6DN90 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with short stature and behavioral abnormalities (Limited), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual developmental disorder with short stature and behavioral abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with short stature and behavioral abnormalities	AR	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	Craniofacial; Neurologic	31607425

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IQSEC1 gene.

• Inborn genetic diseases (61 variants)
• not provided (47 variants)
• Intellectual developmental disorder with short stature and behavioral abnormalities (9 variants)
• Intellectual disability (1 variants)
• Developmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IQSEC1 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				24	6	30
missense		1	67	5	4	77
nonsense						0
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3	2	1	6
Total	0	2	71	31	11

Highest pathogenic variant AF is 0.0000131

Variants in IQSEC1

This is a list of pathogenic ClinVar variants found in the IQSEC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-12899391-TAGG-T		IQSEC1-related disorder	Likely benign (Jul 02, 2020)
3-12901002-C-A		not specified	Uncertain significance (Sep 14, 2021)
3-12901002-C-T		not specified	Uncertain significance (Jun 11, 2021)
3-12901078-C-T			Benign (Jul 16, 2018)
3-12901084-C-T		not specified	Uncertain significance (Dec 27, 2022)
3-12901089-G-A		not specified	Uncertain significance (Jan 03, 2022)
3-12901095-G-A			Uncertain significance (Oct 26, 2023)
3-12901104-C-T		not specified	Uncertain significance (Jan 03, 2024)
3-12901126-C-T			Benign (Dec 31, 2019)
3-12901164-GCGTGCTGGATGTGCTGGGGTGGGT-G		Intellectual developmental disorder with short stature and behavioral abnormalities	Uncertain significance (Apr 04, 2024)
3-12901185-G-A		not specified	Uncertain significance (Dec 06, 2022)
3-12901195-G-A		not specified	Uncertain significance (Apr 07, 2022)
3-12901198-G-A		not specified	Uncertain significance (Oct 25, 2022)
3-12901211-C-T			Benign (Dec 31, 2019)
3-12901250-C-T			Likely benign (Oct 01, 2023)
3-12901258-TGGC-T			Benign (Jan 20, 2023)
3-12901259-G-A			Likely benign (May 01, 2022)
3-12901261-C-G			Benign (Dec 31, 2019)
3-12901262-G-A			Likely benign (Oct 01, 2023)
3-12901289-C-T		IQSEC1-related disorder	Benign/Likely benign (Dec 22, 2022)
3-12901299-C-T		not specified	Uncertain significance (Jun 07, 2023)
3-12901300-C-T		Intellectual developmental disorder with short stature and behavioral abnormalities	Uncertain significance (Feb 02, 2022)
3-12901344-G-A		not specified	Uncertain significance (Dec 12, 2023)
3-12901345-G-A		not specified	Uncertain significance (Aug 04, 2021)
3-12901349-T-G			Likely benign (Aug 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IQSEC1	protein_coding	protein_coding	ENST00000273221	14	175899

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000308	125737	0	9	125746	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	496	661	0.750	0.0000481	6247
Missense in Polyphen		147	251.14	0.58534		2327
Synonymous	-0.112	294	292	1.01	0.0000220	1953
Loss of Function	5.34	4	40.8	0.0980	0.00000208	463

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000937	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000551	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000538	0.0000527
Middle Eastern	0.0000551	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor for ARF1 and ARF6 (PubMed:24058294). Guanine nucleotide exchange factor activity is enhanced by lipid binding (PubMed:24058294). Accelerates GTP binding by ARFs of all three classes. Guanine nucleotide exchange protein for ARF6, mediating internalisation of beta-1 integrin. {ECO:0000269|PubMed:11226253, ECO:0000269|PubMed:16461286, ECO:0000269|PubMed:24058294}.
• Pathway: Endocytosis - Homo sapiens (human);EGF-EGFR Signaling Pathway;Plexin-D1 Signaling;Arf6 signaling events (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.159
• rvis_EVS: -1.26
• rvis_percentile_EVS: 5.34

Haploinsufficiency Scores

• pHI: 0.209
• hipred: Y
• hipred_score: 0.809
• ghis: 0.635

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.207

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Iqsec1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: iqsec1a
• Affected structure: vascular lymphangioblast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: actin cytoskeleton organization;regulation of ARF protein signal transduction;positive regulation of GTPase activity;positive regulation of keratinocyte migration;positive regulation of adherens junction organization
• Cellular component: nucleolus;cytoplasm;membrane;intracellular membrane-bounded organelle
• Molecular function: ARF guanyl-nucleotide exchange factor activity;protein binding;lipid binding