ITSN2

intersectin 2, the group of EF-hand domain containing|C2 domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): 2:24202864-24360536

Previous symbols: [ "SH3D1B" ]

Links

ENSG00000198399 ∙ NCBI:50618 ∙ OMIM:604464 ∙ HGNC:6184 ∙ Uniprot:Q9NZM3 ∙ 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 ITSN2 gene.

• not_specified (217 variants)
• not_provided (169 variants)
• ITSN2-related_disorder (76 variants)
• Landau-Kleffner_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITSN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006277.3. 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			7	48	7	62
missense			276	15	6	297
nonsense			2			2
start loss			2			2
frameshift			2			2
splice donor/acceptor (+/-2bp)			11	1		12
Total	0	0	300	64	13

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITSN2	protein_coding	protein_coding	ENST00000355123	39	157851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125599	1	148	125748	0.000593

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	788	881	0.894	0.0000479	11073
Missense in Polyphen		90	135.5	0.66421		1656
Synonymous	-0.603	333	319	1.04	0.0000168	3129
Loss of Function	6.00	41	108	0.378	0.00000587	1276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00136	0.00135
Ashkenazi Jewish	0.000419	0.000397
East Asian	0.000551	0.000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000649	0.000633
Middle Eastern	0.000551	0.000544
South Asian	0.000741	0.000719
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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 (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:23999003}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;TCR;Clathrin-mediated endocytosis;EGFR1;Cargo recognition for clathrin-mediated endocytosis;Regulation of CDC42 activity (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• loftool: 0.926
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.42

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.634

Gene Damage Prediction

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

Gene ontology

• Biological process: endocytosis;positive regulation of signal transduction;viral process;regulation of Rho protein signal transduction;positive regulation of dendrite extension
• Cellular component: cytoplasm;centrosome;extracellular exosome
• Molecular function: SH3/SH2 adaptor activity;Rho guanyl-nucleotide exchange factor activity;calcium ion binding;protein binding