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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ITSN1
intersectin 1
Chromosome 21 Β· 21q22.11
NCBI Gene: 6453Ensembl: ENSG00000205726.15HGNC: HGNC:6183UniProt: A7XZY7
154PubMed Papers
20Diseases
0Drugs
24Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTransporter
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
proline-rich region bindingintracellular protein localizationnucleoplasmclathrin-coated pitgenetic disorderNeurodevelopmental disorderAutistic behaviorIntellectual disability
✦AI Summary

ITSN1 (intersectin 1) is a multi-domain scaffold protein that plays crucial roles in clathrin-mediated endocytosis and neurodevelopment 1. The protein functions by organizing and stabilizing endocytic protein interaction networks during clathrin-mediated endocytosis, recruiting key proteins including AP2, epsin1, and dynamin2 to facilitate vesicle formation 1. ITSN1 is recruited during endocytic site stabilization and growth phases, and its knockdown impairs endocytic protein recruitment 1. Beyond endocytosis, ITSN1 is critical for brain development and neuronal function 2. Disease-wise, ITSN1 haploinsufficiency is associated with multiple neurological conditions. Loss-of-function variants cause autism spectrum disorders (90% of cases), intellectual disability (86%), and epilepsy (30%) 23. Notably, ITSN1 protein-truncating variants confer substantially increased Parkinson's disease risk (odds ratio 10.5) 4. The clinical significance is substantial, as ITSN1 represents a moderate-risk autism gene with less severe cognitive impairment compared to highly penetrant autism genes 3. Located on chromosome 21, ITSN1 overexpression in Down syndrome may contribute to early-onset Alzheimer's disease through endocytic dysfunction 5.

Sources cited
1
ITSN1 organizes and stabilizes endocytic protein interaction networks during clathrin-mediated endocytosis
PMID: 39580802
2
ITSN1 variants cause autism spectrum disorders (90%), intellectual disability (86%), and epilepsy (30%)
PMID: 34707297
3
ITSN1 is a moderate-risk autism gene with less cognitive impairment than highly penetrant genes
PMID: 35982159
4
ITSN1 protein-truncating variants increase Parkinson's disease risk with odds ratio of 10.5
PMID: 40056900
5
ITSN1 overexpression in Down syndrome may contribute to Alzheimer's disease through endocytic dysfunction
PMID: 16442855
Disease Associationsβ“˜20
genetic disorderOpen Targets
0.53Moderate
Neurodevelopmental disorderOpen Targets
0.45Moderate
Autistic behaviorOpen Targets
0.40Moderate
Intellectual disabilityOpen Targets
0.37Weak
autosomal dominant non-syndromic intellectual disabilityOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.35Weak
2q23.1 microdeletion syndromeOpen Targets
0.34Weak
Generalized-onset seizureOpen Targets
0.27Weak
esophageal atresia/tracheoesophageal fistulaOpen Targets
0.26Weak
Tracheoesophageal fistulaOpen Targets
0.26Weak
auditory system diseaseOpen Targets
0.22Weak
Abruptio PlacentaeOpen Targets
0.22Weak
tooth diseaseOpen Targets
0.22Weak
pericarditisOpen Targets
0.15Weak
polycythemiaOpen Targets
0.15Weak
osteoarthritisOpen Targets
0.15Weak
nephrotic syndromeOpen Targets
0.15Weak
autismOpen Targets
0.12Weak
gliomaOpen Targets
0.09Suggestive
SepsisOpen Targets
0.09Suggestive
Pathogenic Variants24
NM_003024.3(ITSN1):c.1909C>T (p.Arg637Ter)Pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 637
NM_003024.3(ITSN1):c.1954C>T (p.Arg652Ter)Pathogenic
not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 652
NM_003024.3(ITSN1):c.3712C>T (p.Arg1238Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1238
NM_003024.3(ITSN1):c.795_798del (p.Ser266fs)Pathogenic
ITSN1-associated neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 266
NM_003024.3(ITSN1):c.973del (p.Ser324_Val325insTer)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 324
NM_003024.3(ITSN1):c.2400T>G (p.Tyr800Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 800
NM_003024.3(ITSN1):c.2070_2071del (p.Lys691fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 691
NM_003024.3(ITSN1):c.3113G>A (p.Trp1038Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1038
NM_003024.3(ITSN1):c.1271_1272del (p.Glu424fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 424
NM_003024.3(ITSN1):c.1363C>T (p.Gln455Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 455
NM_003024.3(ITSN1):c.1651C>T (p.Gln551Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 551
NM_003024.3(ITSN1):c.4248_4249del (p.Cys1417fs)Pathogenic
Intellectual disability, autosomal dominant 1
β˜…β˜†β˜†β˜†2024β†’ Residue 1417
NM_003024.3(ITSN1):c.3038dup (p.Tyr1013Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1013
NM_003024.3(ITSN1):c.1660C>T (p.Gln554Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 554
NM_003024.3(ITSN1):c.2895C>G (p.Tyr965Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 965
NM_003024.3(ITSN1):c.1102C>T (p.Arg368Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 368
NM_003024.3(ITSN1):c.1333C>T (p.Arg445Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 445
NM_003024.3(ITSN1):c.2772G>A (p.Trp924Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 924
NM_003024.3(ITSN1):c.3937_3941dup (p.Met1314fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 1314
NM_003024.3(ITSN1):c.3017-2A>GLikely pathogenic
Generalized-onset seizure
β˜…β˜†β˜†β˜†2022
View on ClinVar β†—
Related Genes
AMPHProtein interaction100%BIN1Protein interaction100%CDC42Protein interaction100%DNM2Protein interaction100%WIPF1Protein interaction100%CLTCL1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Liver
97%
Heart
83%
Ovary
71%
Bone Marrow
40%
Lung
39%
Gene Interaction Network
Click a node to explore
ITSN1AMPHBIN1CDC42DNM2WIPF1CLTCL1
PROTEIN STRUCTURE
Preparing viewer…
PDB3FIA Β· 1.45 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.30Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.24 [0.18–0.30]
RankingsWhere ITSN1 stands among ~20K protein-coding genes
  • #2,937of 20,598
    Most Researched154 Β· top quartile
  • #2,005of 5,498
    Most Pathogenic Variants24
  • #1,184of 17,882
    Most Constrained (LOEUF)0.30 Β· top 10%
Genes detectedITSN1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes.
PMID: 35982159
Nat Genet Β· 2022
1.00
2
ITSN1: a novel candidate gene involved in autosomal dominant neurodevelopmental disorder spectrum.
PMID: 34707297
Eur J Hum Genet Β· 2022
0.90
3
Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease.
PMID: 40056900
Cell Rep Β· 2025
0.80
4
Further evidence of involvement of ITSN1 in autosomal dominant neurodevelopmental disorder.
PMID: 38346866
Clin Genet Β· 2024
0.70
5
Intersectin1 promotes clathrin-mediated endocytosis by organizing and stabilizing endocytic protein interaction networks.
PMID: 39580802
Cell Rep Β· 2024
0.60