ITSN1

intersectin 1, the group of EF-hand domain containing|C2 domain containing|Dbl family Rho GEFs|Pleckstrin homology domain containing

Basic information

Region (hg38): 21:33642400-33899861

Previous symbols: [ "SH3D1A", "ITSN" ]

Links

ENSG00000205726 ∙ NCBI:6453 ∙ OMIM:602442 ∙ HGNC:6183 ∙ Uniprot:Q15811 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITSN1 gene.

• Inborn_genetic_diseases (156 variants)
• not_provided (131 variants)
• ITSN1-related_disorder (55 variants)
• Autistic_behavior (9 variants)
• Neurodevelopmental_disorder (5 variants)
• not_specified (5 variants)
• Nephrotic_syndrome (2 variants)
• Esophageal_atresia/tracheoesophageal_fistula (1 variants)
• ITSN1-related_neurodevelopmental_disorders (1 variants)
• Autism (1 variants)
• ITSN1-related_neurodevelopmental_disorder (1 variants)
• Generalized-onset_seizure (1 variants)
• Intellectual_disability,_autosomal_dominant_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITSN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003024.3. 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	27	2	30
missense		1	234	17	1	253
nonsense	9	4	7			20
start loss						0
frameshift	6	3	5			14
splice donor/acceptor (+/-2bp)		2	2			4
Total	15	10	249	44	3

Highest pathogenic variant AF is 0.00006439426

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITSN1	protein_coding	protein_coding	ENST00000381318	39	257460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.25e-7	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.61	644	959	0.672	0.0000542	11253
Missense in Polyphen		136	276.57	0.49173		3302
Synonymous	0.341	356	364	0.977	0.0000218	3263
Loss of Function	8.30	16	110	0.146	0.00000600	1195

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000314	0.000304
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000164	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000116	0.000114
Middle Eastern	0.000164	0.000163
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) specific for the CDC42 GTPase (By similarity). Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1. {ECO:0000250, ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:22648170}.
• Pathway: Developmental Biology;Signaling by GPCR;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;EPH-Ephrin signaling;EPHB-mediated forward signaling;Rho GTPase cycle;Signaling by Rho GTPases;Clathrin-mediated endocytosis;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Cargo recognition for clathrin-mediated endocytosis;Axon guidance;G alpha (12/13) signalling events;GPCR downstream signalling;Regulation of CDC42 activity;Internalization of ErbB1;EPHB forward signaling;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Recessive Scores

• pRec: 0.202

Intolerance Scores

• loftool: 0.512
• rvis_EVS: -2.01
• rvis_percentile_EVS: 1.72

Haploinsufficiency Scores

• pHI: 0.718
• hipred: Y
• hipred_score: 0.756
• ghis: 0.570

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itsn1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;small GTPase mediated signal transduction;viral process;positive regulation of kinase activity;regulation of Rho protein signal transduction;positive regulation of apoptotic process;negative regulation of neuron apoptotic process;ephrin receptor signaling pathway;synaptic vesicle endocytosis;regulation of small GTPase mediated signal transduction;positive regulation of protein kinase B signaling;membrane organization
• Cellular component: cytosol;plasma membrane;clathrin-coated pit;lamellipodium;cell junction;endocytic vesicle;calyx of Held;presynaptic endocytic zone
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;calcium ion binding;protein binding;kinase activator activity;protein-containing complex scaffold activity;proline-rich region binding