IQSEC1

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

Basic information

Region (hg38): 3:12897043-13283281

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
intellectual developmental disorder with short stature and behavioral abnormalities (Strong), mode of inheritance: AR
intellectual developmental disorder with short stature and behavioral abnormalities (Limited), 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.

not_specified (168 variants)
not_provided (59 variants)
Intellectual_developmental_disorder_with_short_stature_and_behavioral_abnormalities (14 variants)
IQSEC1-related_disorder (4 variants)
Neurodevelopmental_abnormality (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. These statistics are base on transcript: NM_001134382.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				36 clinvar	6 clinvar	42
missense	1 clinvar	1 clinvar	170 clinvar	7 clinvar	4 clinvar	183
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	2	172	43	10

Highest pathogenic variant AF is 0.000014325487

Loading clinvar variants...

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