ITSN1

Chr 21

intersectin 1

Also known as: ITSN, SH3D1A, SH3P17

NCBI Gene: 6453 ENSG00000205726 UniProt: Q15811 OMIM: 602442

The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOEUF 0.22

Clinical Summary— ITSN1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 296 VUS of 467 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 8.30

OE 0.15 (0.10–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.61Z-score

OE missense 0.67 (0.63–0.72)

644 obs / 958.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.15 (0.10–0.22)

0≤0.351.4

Missense OE?0.67 (0.63–0.72)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 16 / 109.9Missense obs/exp: 644 / 958.9Syn Z: 0.34

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic8

VUS296

Likely Benign58

Benign53

Conflicting3

Pathogenic

Likely Pathogenic

296

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	0	1	0	17
Likely Pathogenic	7	1	0	0	8
VUS	18	271	6	1	296
Likely Benign	0	18	11	29	58
Benign	0	2	45	6	53
Conflicting	—				3
Total	41	292	63	36	435

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

63 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap ITSN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →