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GeneE
7 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.
DYNC1I2
dynein cytoplasmic 1 intermediate chain 2
Chromosome 2 Β· 2q31.1
NCBI Gene: 1781Ensembl: ENSG00000077380.17HGNC: HGNC:2964UniProt: A0A140VKE9
146PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
centrosomemicrotubulevesicleprotein bindingneurodevelopmental disorder with microcephaly and structural brain anomaliesneurodegenerative diseaseviral diseaselysosomal storage disease
✦AI Summary

DYNC1I2 (dynein cytoplasmic 1 intermediate chain 2) encodes a non-catalytic accessory component of the cytoplasmic dynein 1 complex that mediates cargo binding and dynein motor function 1. As an intermediate chain, DYNC1I2 links dynein to dynactin and adapter proteins, facilitating retrograde intracellular transport of vesicles and organelles along microtubules, including Golgi apparatus, late endosomes, and lysosomes 1. DYNC1I2 specifically interacts with TMEM39A to regulate lysosome distribution and positioning in cells 2. Bi-allelic DYNC1I2 variants cause autosomal-recessive neurodevelopmental disorder with microcephaly and structural brain anomalies 13. Pathogenic variants impair neurogenesis through disrupted cargo transport essential for neuronal development 1. Functional studies in zebrafish demonstrate that dync1i2 dysfunction causes abnormal spindle morphology, increased apoptosis during prolonged mitosis, and altered craniofacial patterning with reduced head size 1. At the molecular level, DYNC1I2 is regulated post-transcriptionally; the lncRNA HHIP-AS1 protects DYNC1I2 mRNA from miR-425-5p-mediated degradation, enabling pro-mitotic effects in SHH-driven tumors 4. Alternative splicing generates tissue-specific DYNC1I2 isoforms with distinct roles in neuronal dynein complexes 5. These findings establish DYNC1I2 as critical for both normal neurodevelopment and microtubule-dependent cellular processes.

Sources cited
1
DYNC1I2 is a component of cytoplasmic dynein 1 complex involved in cargo transport; bi-allelic variants cause syndromic microcephaly with intellectual disability, cerebral malformations, and impaired mitotic spindle morphology
PMID: 31079899
2
DYNC1I2 (mammalian ortholog of C. elegans DYNC1I2) interacts with TMEM39A to regulate lysosome distribution and positioning
PMID: 33531362
3
HHIP-AS1 lncRNA stabilizes DYNC1I2 mRNA by preventing degradation by miR-425-5p, promoting mitotic spindle assembly and tumorigenicity in SHH-driven tumors
PMID: 35831316
4
DYNC1I2 splice site variant (c.607+1G>A) identified in consanguineous families with neurodevelopmental disorders and primary microcephaly (OMIM 618492)
PMID: 39281811
5
DYNC1I2 undergoes complex alternative splicing with tissue-specific isoforms, particularly in nervous system, essential for different dynein complex functions
PMID: 20657784
Disease Associationsβ“˜21
neurodevelopmental disorder with microcephaly and structural brain anomaliesOpen Targets
0.70Moderate
neurodegenerative diseaseOpen Targets
0.48Moderate
viral diseaseOpen Targets
0.46Moderate
lysosomal storage diseaseOpen Targets
0.43Moderate
neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomaliesOpen Targets
0.43Moderate
Alzheimer diseaseOpen Targets
0.32Weak
multiple sclerosisOpen Targets
0.32Weak
Parkinson diseaseOpen Targets
0.32Weak
smoking initiationOpen Targets
0.31Weak
PainOpen Targets
0.30Weak
obesityOpen Targets
0.29Weak
tuberculosisOpen Targets
0.29Weak
insomniaOpen Targets
0.17Weak
mathematical abilityOpen Targets
0.17Weak
hypertriglyceridemia 2Open Targets
0.03Suggestive
schizophreniaOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
Mobius syndromeOpen Targets
0.02Suggestive
Neurodevelopmental disorder with microcephaly and structural brain anomaliesUniProt
Pathogenic Variants5
NM_001378.3(DYNC1I2):c.49C>T (p.Arg17Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 17
NM_001378.3(DYNC1I2):c.740A>G (p.Tyr247Cys)Pathogenic
Neurodevelopmental disorder with microcephaly and structural brain anomalies|Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies
β˜…β˜†β˜†β˜†2020β†’ Residue 247
NM_001378.3(DYNC1I2):c.868C>T (p.Gln290Ter)Pathogenic
Neurodevelopmental disorder with microcephaly and structural brain anomalies|Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies
β˜…β˜†β˜†β˜†2020β†’ Residue 290
NM_001378.3(DYNC1I2):c.871-1G>ALikely pathogenic
Neurodevelopmental disorder with microcephaly and structural brain anomalies
β˜…β˜†β˜†β˜†2019
NM_001378.3(DYNC1I2):c.607+1G>APathogenic
Neurodevelopmental disorder with microcephaly and structural brain anomalies
β˜†β˜†β˜†β˜†2019
View on ClinVar β†—
Related Genes
ACTR10Protein interaction100%DCTN2Protein interaction100%DCTN5Protein interaction100%DCTN4Protein interaction100%DCTN3Protein interaction100%ACTR1AProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
40%
Ovary
37%
Lung
33%
Liver
17%
Bone Marrow
14%
Gene Interaction Network
Click a node to explore
DYNC1I2ACTR10DCTN2DCTN5DCTN4DCTN3ACTR1A
PROTEIN STRUCTURE
Preparing viewer…
PDB7Z8I Β· 3.30 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.84LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.64 [0.49–0.84]
RankingsWhere DYNC1I2 stands among ~20K protein-coding genes
  • #3,101of 20,598
    Most Researched146 Β· top quartile
  • #3,500of 5,498
    Most Pathogenic Variants5
  • #7,225of 17,882
    Most Constrained (LOEUF)0.84
Genes detectedDYNC1I2
Sources retrieved7 papers
Response timeβ€”
πŸ“„ Sources
7β–Ό
1
The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors.
PMID: 35831316
Nat Commun Β· 2022
1.00
2
The genetic cause of neurodevelopmental disorders in 30 consanguineous families.
PMID: 39281811
Front Med (Lausanne) Β· 2024
0.86
3
The conserved autoimmune-disease risk gene
PMID: 33531362
Proc Natl Acad Sci U S A Β· 2021
0.71
4
Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features.
PMID: 31079899
Am J Hum Genet Β· 2019
0.57
5
Mouse cytoplasmic dynein intermediate chains: identification of new isoforms, alternative splicing and tissue distribution of transcripts.
PMID: 20657784
PLoS One Β· 2010
0.43