DYNC1I2

Summary

DYNC1I2 (dynein cytoplasmic 1 intermediate chain 2, HGNC:2964) is a protein-coding gene on chromosome 2q31.1, encoding Cytoplasmic dynein 1 intermediate chain 2 (Q13409). Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

This gene encodes a member of the dynein intermediate chain family. The encoded protein is a non-catalytic component of the cytoplasmic dynein 1 complex, which acts as a retrograde microtubule motor to transport organelles and vesicles. A pseudogene of this gene is located on chromosome 10. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1781 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with microcephaly and structural brain anomalies (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 122 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_001378

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2964
Approved symbol	DYNC1I2
Name	dynein cytoplasmic 1 intermediate chain 2
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	DIC74
Ensembl gene	ENSG00000077380
Ensembl biotype	protein_coding
OMIM	603331
Entrez	1781

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 49 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000340296, ENST00000397119, ENST00000409197, ENST00000409317, ENST00000409453, ENST00000409773, ENST00000410079, ENST00000411953, ENST00000412370, ENST00000422646, ENST00000423910, ENST00000425485, ENST00000430778, ENST00000435234, ENST00000438879, ENST00000443458, ENST00000445378, ENST00000452242, ENST00000456808, ENST00000470286, ENST00000471482, ENST00000476551, ENST00000479806, ENST00000482454, ENST00000508530, ENST00000869658, ENST00000869659, ENST00000869660, ENST00000869661, ENST00000869662, ENST00000869663, ENST00000869664, ENST00000869665, ENST00000869666, ENST00000869667, ENST00000869668, ENST00000869669, ENST00000869670, ENST00000869671, ENST00000869672, ENST00000869673, ENST00000869674, ENST00000933315, ENST00000933316, ENST00000933317, ENST00000933318, ENST00000959545, ENST00000959546, ENST00000959547, ENST00000959548, ENST00000959549, ENST00000959550, ENST00000959551, ENST00000959552, ENST00000959553

RefSeq mRNA: 12 — MANE Select: NM_001378 NM_001271785, NM_001271786, NM_001271787, NM_001271788, NM_001271789, NM_001271790, NM_001320882, NM_001320883, NM_001320884, NM_001378, NM_001378455, NM_001378456

CCDS: CCDS46450, CCDS63054, CCDS63056, CCDS63057, CCDS82533

Canonical transcript exons

ENST00000397119 — 18 exons

Exon	Start	End
ENSE00001632050	171707287	171707377
ENSE00001927290	171687469	171687627
ENSE00002185937	171692777	171692894
ENSE00002525492	171706547	171706564
ENSE00003485477	171744049	171744189
ENSE00003502382	171745802	171745927
ENSE00003514314	171726791	171726916
ENSE00003558811	171727821	171727967
ENSE00003586538	171712767	171712826
ENSE00003612976	171728717	171728850
ENSE00003614530	171726194	171726293
ENSE00003621042	171729709	171729853
ENSE00003637662	171715328	171715443
ENSE00003656849	171728305	171728418
ENSE00003660433	171690147	171690263
ENSE00003694341	171747776	171750158
ENSE00003787575	171725618	171725713
ENSE00003789069	171725919	171726081

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 132.4893 / max 2861.7997, expressed in 1824 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23676	83.4763	1823
23673	37.4366	1806
23677	3.9444	1295
23674	3.8518	1526
23672	1.5645	990
23671	1.4383	919
23675	0.7774	441

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.25	gold quality
cortical plate	UBERON:0005343	99.21	gold quality
ganglionic eminence	UBERON:0004023	99.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.69	gold quality
ventricular zone	UBERON:0003053	98.49	gold quality
sural nerve	UBERON:0015488	97.88	gold quality
smooth muscle tissue	UBERON:0001135	97.64	gold quality
adrenal tissue	UBERON:0018303	97.31	gold quality
islet of Langerhans	UBERON:0000006	97.28	gold quality
popliteal artery	UBERON:0002250	97.28	gold quality
tibial artery	UBERON:0007610	97.28	gold quality
descending thoracic aorta	UBERON:0002345	97.08	gold quality
right coronary artery	UBERON:0001625	96.89	gold quality
aorta	UBERON:0000947	96.88	gold quality
colonic epithelium	UBERON:0000397	96.84	gold quality
rectum	UBERON:0001052	96.81	gold quality
gall bladder	UBERON:0002110	96.80	gold quality
thoracic aorta	UBERON:0001515	96.73	gold quality
ascending aorta	UBERON:0001496	96.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.68	gold quality
body of uterus	UBERON:0009853	96.60	gold quality
lower esophagus	UBERON:0013473	96.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.53	gold quality
left coronary artery	UBERON:0001626	96.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.46	gold quality
ectocervix	UBERON:0012249	96.37	gold quality
right lung	UBERON:0002167	96.33	gold quality
tibial nerve	UBERON:0001323	96.23	gold quality
endocervix	UBERON:0000458	96.12	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.88
E-GEOD-93593	no	6.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

126 targeting DYNC1I2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Using mouse cells as a model, show that Par3 associates with dynein by interacting with dynein light intermediate chain 2. (PMID:19540120)
• SQSTM1 is required for proper dynein motility and trafficking along microtubules. (PMID:25015291)
• Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features. (PMID:31079899)
• Dynein intermediate chain 2c (DNCI2c) complex is essential for exiting Mad2-dependent spindle assembly checkpoint. (PMID:34400173)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	dync1i2a	ENSDARG00000078386
danio_rerio	dync1i2b	ENSDARG00000103195
mus_musculus	Dync1i2	ENSMUSG00000027012
rattus_norvegicus	Dync1i2	ENSRNOG00000009781
drosophila_melanogaster	sw	FBGN0003654
drosophila_melanogaster	Sdic3	FBGN0052823
drosophila_melanogaster	Sdic2	FBGN0053497
drosophila_melanogaster	Sdic4	FBGN0053499
drosophila_melanogaster	Sdic1	FBGN0067861
drosophila_melanogaster	SdicA	FBGN0283432
drosophila_melanogaster	SdicB	FBGN0283433
drosophila_melanogaster	SdicC	FBGN0283434
caenorhabditis_elegans		WBGENE00015927

Paralogs (7): DYNC2I2 (ENSG00000119333), DNAI1 (ENSG00000122735), DYNC2I1 (ENSG00000126870), DNAI4 (ENSG00000152763), DYNC1I1 (ENSG00000158560), DNAI3 (ENSG00000162643), DNAI2 (ENSG00000171595)

Protein

Protein identifiers

Cytoplasmic dynein 1 intermediate chain 2 — Q13409 (reviewed: Q13409)

Alternative names: Cytoplasmic dynein intermediate chain 2, Dynein intermediate chain 2, cytosolic

All UniProt accessions (14): Q13409, A0A140VKE9, E7EMU4, E7EQL5, E7EQU2, E7ERH4, E7ERR6, E7ESD3, E7ET01, E7ETL8, E7EU01, E7EUM4, E7EV09, E9PGG1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1. Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes.

Subunit / interactions. Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNLT3. Interacts with DYNLT1. Interacts (dephosphorylated at Ser-90) with DCTN1. Interacts with BICD2. Interacts with SPEF2. Interacts with CFAP61. (Microbial infection) Interacts with human adenovirus 5 hexon protein; this interaction probably allows virus intracellular transport.

Subcellular location. Cytoplasm. Cytoskeleton.

Post-translational modifications. The phosphorylation status of Ser-90 appears to be involved in dynactin-dependent target binding. Pyrophosphorylation by 5-diphosphoinositol pentakisphosphate (5-IP7) promotes interaction with DCTN1. Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue.

Disease relevance. Neurodevelopmental disorder with microcephaly and structural brain anomalies (NEDMIBA) [MIM:618492] An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, microcephaly, dysmorphic facial features, and cerebral malformations including simplification of cerebral gyration, agenesis of the corpus callosum, and brainstem and white matter hypoplasia. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the dynein intermediate chain family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q13409-1	2A	yes
Q13409-2	2B
Q13409-3	2C
Q13409-5	2E
Q13409-6	2F
Q13409-7	3

RefSeq proteins (12): NP_001258714, NP_001258715, NP_001258716, NP_001258717, NP_001258718, NP_001258719, NP_001307811, NP_001307812, NP_001307813, NP_001365384, NP_001365385, NP_001369* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR025956	DYNC1I1/DYNC1I2	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050687	Dynein_IC	Family

Pfam: PF00400, PF11540

UniProt features (88 total): strand 41, modified residue 17, repeat 7, compositionally biased region 4, splice variant 4, helix 4, sequence variant 3, sequence conflict 3, region of interest 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
7Z8I	ELECTRON MICROSCOPY	3.3
6F1U	ELECTRON MICROSCOPY	3.4
6F1Z	ELECTRON MICROSCOPY	3.4
6F1T	ELECTRON MICROSCOPY	3.5
9BLY	ELECTRON MICROSCOPY	3.5
8PR2	ELECTRON MICROSCOPY	3.8
8PR3	ELECTRON MICROSCOPY	3.9
7Z8J	ELECTRON MICROSCOPY	3.93
9YNC	ELECTRON MICROSCOPY	3.93
9YNG	ELECTRON MICROSCOPY	4.07
8PQW	ELECTRON MICROSCOPY	4.2
9YND	ELECTRON MICROSCOPY	4.26
7Z8K	ELECTRON MICROSCOPY	4.37
9E28	ELECTRON MICROSCOPY	4.4
9E12	ELECTRON MICROSCOPY	4.5
9E13	ELECTRON MICROSCOPY	4.5
9E14	ELECTRON MICROSCOPY	5
8PQZ	ELECTRON MICROSCOPY	5.5
9YNH	ELECTRON MICROSCOPY	5.5
9E23	ELECTRON MICROSCOPY	6.2
9HHL	ELECTRON MICROSCOPY	6.53
6F38	ELECTRON MICROSCOPY	6.7
6F3A	ELECTRON MICROSCOPY	8.2
8PR1	ELECTRON MICROSCOPY	8.2
9YNE	ELECTRON MICROSCOPY	8.46
8PR0	ELECTRON MICROSCOPY	9.4
8PTK	ELECTRON MICROSCOPY	10
7Z8F	ELECTRON MICROSCOPY	20
5JPW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13409-F1	73.03	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (17): 2, 51, 51, 90, 95, 97, 101, 104, 73, 81, 84, 73, 81, 84, 73, 81, 84

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9609690	HCMV Early Events
R-HSA-9646399	Aggrephagy
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 369 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GCM_MAP4K4, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, MORF_MBD4, GCM_GSPT1, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_CHROMOSOME_SEPARATION, REACTOME_MEMBRANE_TRAFFICKING, CHANDRAN_METASTASIS_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (3): microtubule-based movement (GO:0007018), transport along microtubule (GO:0010970), positive regulation of intracellular transport (GO:0032388)

GO Molecular Function (4): microtubule motor activity (GO:0003777), dynein light chain binding (GO:0045503), dynein heavy chain binding (GO:0045504), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasmic dynein complex (GO:0005868), microtubule (GO:0005874), vesicle (GO:0031982), cytoskeleton (GO:0005856), dynein complex (GO:0030286)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Mitotic Prometaphase	3
G2/M Transition	2
Centrosome maturation	2
Amplification of signal from the kinetochores	1
Adaptive Immune System	1
Mitotic Anaphase	1
Cellular responses to stress	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
M Phase	1
HCMV Infection	1
Selective autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
microtubule-based process	1
microtubule-based movement	1
cytoskeleton-dependent intracellular transport	1
microtubule-based transport	1
regulation of intracellular transport	1
intracellular transport	1
positive regulation of cellular process	1
positive regulation of transport	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
binding	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane-bounded organelle	1
intracellular membraneless organelle	1
microtubule associated complex	1
catalytic complex	1

Protein interactions and networks

STRING

1874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNC1I2	DYNC1H1	Q14204	929
DYNC1I2	DYNLL1	P63167	808
DYNC1I2	DYNC1LI2	O43237	776
DYNC1I2	CDKN1C	P49918	759
DYNC1I2	DCTN2	Q13561	753
DYNC1I2	KCNQ1	P51787	740
DYNC1I2	PHLDA2	Q53GA4	700
DYNC1I2	DYNC1LI1	Q9Y6G9	697
DYNC1I2	TWNK	Q96RR1	687
DYNC1I2	DCTN1	Q14203	675
DYNC1I2	DYNLT2	Q8IZS6	671
DYNC1I2	DYNLT1	P63172	652
DYNC1I2	DYNLRB1	Q9NP97	636
DYNC1I2	DNAL1	Q4LDG9	634
DYNC1I2	DYNLL2	Q96FJ2	628

IntAct

88 interactions, top by confidence:

A	B	Type	Score
DYNC1I2	DYNLRB1	psi-mi:“MI:0915”(physical association)	0.750
DYNLRB1	DYNC1I2	psi-mi:“MI:0915”(physical association)	0.750
DYNC1I2	DYNLT3	psi-mi:“MI:0915”(physical association)	0.750
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DYNC1H1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.530
DYNC1LI1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.530
ITK	GAPDHS	psi-mi:“MI:0914”(association)	0.530
DYNC1LI1	DYNC1I2	psi-mi:“MI:0914”(association)	0.530
DYNLL2	SHMT2	psi-mi:“MI:0914”(association)	0.510
PAFAH1B1	DYNLT3	psi-mi:“MI:0914”(association)	0.510
vpr	AGPS	psi-mi:“MI:0914”(association)	0.460
vpr	ANKRD17	psi-mi:“MI:0914”(association)	0.460
DYNC1I2	NPM1	psi-mi:“MI:0915”(physical association)	0.400
Dynll1		psi-mi:“MI:0915”(physical association)	0.400
Dync1h1	DYNLT3	psi-mi:“MI:0915”(physical association)	0.400
Dync1i2	DYNLT3	psi-mi:“MI:0915”(physical association)	0.400
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (458): DYNLRB1 (Two-hybrid), DYNC1I2 (Affinity Capture-MS), DYNLT3 (Two-hybrid), ADD1 (Co-fractionation), ADD3 (Co-fractionation), AHNAK2 (Co-fractionation), DCTN1 (Co-fractionation), DYNC1H1 (Co-fractionation), DYNC1I2 (Co-fractionation), DYNC1LI1 (Co-fractionation), DYNC1LI2 (Co-fractionation), DYNLRB2 (Co-fractionation), PSMA2 (Co-fractionation), PSMA5 (Co-fractionation), DYNC1I2 (Affinity Capture-MS)

ESM2 similar proteins: A2AC93, B2RY71, E7F6H7, E9PYY5, E9Q5M6, O14576, O43815, O55106, O88485, O88487, P27766, P36872, P70483, Q0III3, Q13409, Q13610, Q16959, Q16960, Q29RQ3, Q2HJ56, Q32KS2, Q32LP9, Q4QR00, Q4V8G4, Q5DQR4, Q5NVM2, Q5SQE2, Q5VTH9, Q5XIL8, Q5ZLK1, Q62871, Q63100, Q66HC9, Q6GPB9, Q8BPM2, Q8C0M8, Q8C0P5, Q8IVH8, Q8IWG1, Q92828

Diamond homologs: E7F6H7, O14576, O88485, O88487, O94518, P54703, Q0III3, Q13409, Q24246, Q29RQ3, Q5NVM2, Q62871, Q63100

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	DYNC1I2	phosphorylation
TRIM58	“down-regulates quantity by destabilization”	DYNC1I2	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Aggrephagy	10	43.5×	1e-12
COPI-independent Golgi-to-ER retrograde traffic	11	40.1×	2e-13
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	10	34.0×	1e-11
Loss of Nlp from mitotic centrosomes	9	25.0×	3e-09
Loss of proteins required for interphase microtubule organization from the centrosome	9	25.0×	3e-09
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	12	24.5×	3e-12
AURKA Activation by TPX2	9	24.0×	3e-09
EML4 and NUDC in mitotic spindle formation	14	22.8×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of microtubule polymerization	5	46.8×	1e-05
microtubule-based movement	6	24.6×	3e-05
microtubule cytoskeleton organization	9	15.2×	3e-06
intracellular protein localization	6	8.7×	3e-03
cell division	11	7.0×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

122 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	79
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2817809	NM_001378.3(DYNC1I2):c.49C>T (p.Arg17Ter)	Pathogenic
635399	NM_001378.3(DYNC1I2):c.607+1G>A	Pathogenic
635400	NM_001378.3(DYNC1I2):c.740A>G (p.Tyr247Cys)	Pathogenic
635401	NM_001378.3(DYNC1I2):c.868C>T (p.Gln290Ter)	Pathogenic
1324307	NM_001378.3(DYNC1I2):c.871-1G>A	Likely pathogenic

SpliceAI

2824 predictions. Top by Δscore:

Variant	Effect	Δscore
2:171690142:CTAAG:C	acceptor_loss	1.0000
2:171690144:A:AG	acceptor_gain	1.0000
2:171690144:AAG:A	acceptor_gain	1.0000
2:171690145:A:G	acceptor_gain	1.0000
2:171690146:G:GA	acceptor_loss	1.0000
2:171690251:G:GT	donor_gain	1.0000
2:171690252:A:T	donor_gain	1.0000
2:171690259:AAGAA:A	donor_gain	1.0000
2:171690260:AGAA:A	donor_gain	1.0000
2:171690261:GAA:G	donor_gain	1.0000
2:171690261:GAAG:G	donor_gain	1.0000
2:171690262:AA:A	donor_gain	1.0000
2:171690263:AGT:A	donor_loss	1.0000
2:171690264:G:GG	donor_gain	1.0000
2:171690265:T:A	donor_loss	1.0000
2:171702366:GC:G	donor_gain	1.0000
2:171702367:C:G	donor_gain	1.0000
2:171707285:A:AG	acceptor_gain	1.0000
2:171707286:G:GG	acceptor_gain	1.0000
2:171715313:A:AG	acceptor_gain	1.0000
2:171715314:T:G	acceptor_gain	1.0000
2:171715317:A:AG	acceptor_gain	1.0000
2:171715318:C:G	acceptor_gain	1.0000
2:171715321:A:AG	acceptor_gain	1.0000
2:171715322:A:G	acceptor_gain	1.0000
2:171715324:TTA:T	acceptor_loss	1.0000
2:171715325:TA:T	acceptor_loss	1.0000
2:171715326:A:AG	acceptor_gain	1.0000
2:171715326:AGAC:A	acceptor_gain	1.0000
2:171715327:G:GA	acceptor_gain	1.0000

AlphaMissense

4207 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:171690187:T:C	L11S	1.000
2:171690193:G:C	R13P	1.000
2:171690195:A:G	K14E	1.000
2:171690197:G:C	K14N	1.000
2:171690197:G:T	K14N	1.000
2:171690205:G:C	R17P	1.000
2:171690208:T:C	L18P	1.000
2:171690210:G:C	A19P	1.000
2:171690214:A:C	Q20P	1.000
2:171690217:T:C	I21T	1.000
2:171690217:T:G	I21S	1.000
2:171690221:A:C	R22S	1.000
2:171690221:A:T	R22S	1.000
2:171726262:G:C	R280P	1.000
2:171726851:G:C	G311R	1.000
2:171726852:G:A	G311D	1.000
2:171726866:T:A	W316R	1.000
2:171726866:T:C	W316R	1.000
2:171727851:T:C	F343L	1.000
2:171727853:T:A	F343L	1.000
2:171727853:T:G	F343L	1.000
2:171727867:T:A	V348D	1.000
2:171727872:G:C	G350R	1.000
2:171727873:G:A	G350D	1.000
2:171727875:G:C	G351R	1.000
2:171727876:G:A	G351D	1.000
2:171727887:G:C	G355R	1.000
2:171727888:G:A	G355D	1.000
2:171727888:G:T	G355V	1.000
2:171727900:T:C	L359P	1.000

dbSNP variants (sampled 300 via entrez): RS1000068600 (2:171750274 G>A), RS1000110289 (2:171726713 A>T), RS1000143660 (2:171708810 A>T), RS1000145404 (2:171697192 GT>G,GTT,GTTTTTT), RS1000184250 (2:171745979 G>A), RS1000186840 (2:171699248 A>C,G), RS1000198203 (2:171698826 G>A), RS1000203519 (2:171694022 C>T), RS1000264821 (2:171713264 A>C,G), RS1000356502 (2:171718694 A>G,T), RS1000365087 (2:171713025 A>G), RS1000532082 (2:171700627 T>C), RS1000605583 (2:171724566 C>T), RS1000683557 (2:171738301 C>A,T), RS1000730965 (2:171738737 T>C)

Disease associations

OMIM: gene MIM:603331 | disease phenotypes: MIM:618492, MIM:617481

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly and structural brain anomalies	Strong	Autosomal recessive

Mondo (2): neurodevelopmental disorder with microcephaly and structural brain anomalies (MONDO:0032779), neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (MONDO:0060490)

Orphanet (2): Microcephaly-corpus callosum hypoplasia-simplified gyral pattern-intellectual disability syndrome (Orphanet:699844), PRUNE1-related neurological syndrome (Orphanet:544469)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000414	Bulbous nose
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000520	Proptosis
HP:0000582	Upslanted palpebral fissure
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001274	Agenesis of corpus callosum
HP:0001290	Generalized hypotonia
HP:0001331	Absent septum pellucidum
HP:0001347	Hyperreflexia
HP:0001611	Hypernasal speech
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002365	Hypoplasia of the brainstem
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0009879	Simplified gyral pattern
HP:0010864	Severe intellectual disability
HP:0011344	Severe global developmental delay

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002761_2	Hippocampal volume	9.000000e-07
GCST008152_69	Weight	2.000000e-06
GCST009391_411	Metabolite levels	6.000000e-06
GCST010002_404	Refractive error	2.000000e-39

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004338	body weight
EFO:0010387	phosphatidylcholine 38:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295815 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	Kd	2.384	nM	CHEMBL5653589
8.62	ED50	2.384	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148271: Binding affinity to human DYNC1I2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0024	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, affects expression, increases abundance	3
bisphenol F	affects cotreatment, increases expression	2
sodium arsenite	decreases methylation, increases expression, decreases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression, increases expression	1
FR900359	affects phosphorylation	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tetrahydropalmatine	decreases expression	1
perfluorooctanoic acid	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118570	Binding	Binding affinity to DYNC1I2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.