DNAI3

Summary

DNAI3 (dynein axonemal intermediate chain 3, HGNC:30711) is a protein-coding gene on chromosome 1p22.3, encoding Dynein axonemal intermediate chain 3 (Q8IWG1). Acts as a negative regulator of cell migration, invasion, and metastasis downstream of p53/TP53, through inhibition of Arp2/3 complex-mediated actin polymerization.

Enables Arp2/3 complex binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation and negative regulation of cell migration. Located in cytoplasm.

Source: NCBI Gene 126820 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 142 total — 1 likely-pathogenic
• MANE Select transcript: NM_145172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30711
Approved symbol	DNAI3
Name	dynein axonemal intermediate chain 3
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	DIC3, FLJ30067, NYD-SP29
Ensembl gene	ENSG00000162643
Ensembl biotype	protein_coding
OMIM	617968
Entrez	126820

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000294664, ENST00000326813, ENST00000370596, ENST00000464801, ENST00000484007, ENST00000528899, ENST00000964695

RefSeq mRNA: 2 — MANE Select: NM_145172 NM_001288563, NM_145172

CCDS: CCDS702, CCDS72818

Canonical transcript exons

ENST00000294664 — 23 exons

Exon	Start	End
ENSE00001067219	85094431	85094555
ENSE00001067221	85082300	85082404
ENSE00001067225	85085831	85086030
ENSE00001067231	85084546	85084695
ENSE00001067236	85073054	85073092
ENSE00001067248	85093458	85093648
ENSE00001067249	85081234	85081415
ENSE00001067252	85090116	85090232
ENSE00001453113	85132855	85133138
ENSE00001950672	85062327	85062486
ENSE00002179324	85071928	85072005
ENSE00003505386	85129990	85130112
ENSE00003528303	85097569	85097655
ENSE00003530071	85104524	85104597
ENSE00003533367	85126511	85126715
ENSE00003559450	85098530	85098658
ENSE00003566484	85108033	85108177
ENSE00003575349	85117729	85117859
ENSE00003578029	85110048	85110135
ENSE00003584019	85128708	85128799
ENSE00003597149	85121751	85121814
ENSE00003620370	85095931	85096020
ENSE00003661126	85124121	85124251

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 96.78.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1382 / max 94.1018, expressed in 828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3813	1.2523	554
3812	0.7029	384
3814	0.1830	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	96.78	gold quality
bronchus	UBERON:0002185	95.16	gold quality
right uterine tube	UBERON:0001302	91.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.10	gold quality
right adrenal gland cortex	UBERON:0035827	86.84	gold quality
caput epididymis	UBERON:0004358	84.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.09	gold quality
right adrenal gland	UBERON:0001233	83.95	gold quality
left testis	UBERON:0004533	83.63	gold quality
oviduct epithelium	UBERON:0004804	83.28	gold quality
right testis	UBERON:0004534	82.97	gold quality
adrenal cortex	UBERON:0001235	82.84	gold quality
left adrenal gland	UBERON:0001234	82.65	gold quality
left adrenal gland cortex	UBERON:0035825	82.65	gold quality
testis	UBERON:0000473	81.58	gold quality
adrenal gland	UBERON:0002369	80.03	gold quality
sperm	CL:0000019	76.70	gold quality
fallopian tube	UBERON:0003889	76.63	gold quality
epithelium of nasopharynx	UBERON:0001951	74.04	gold quality
nasopharynx	UBERON:0001728	74.03	gold quality
stromal cell of endometrium	CL:0002255	72.19	gold quality
adenohypophysis	UBERON:0002196	71.55	gold quality
nasal cavity epithelium	UBERON:0005384	71.21	silver quality
pituitary gland	UBERON:0000007	70.38	gold quality
right lung	UBERON:0002167	69.51	gold quality
cauda epididymis	UBERON:0004360	67.17	silver quality
nasal cavity mucosa	UBERON:0001826	67.06	gold quality
corpus epididymis	UBERON:0004359	66.27	gold quality
adult organism	UBERON:0007023	61.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.50
E-MTAB-9388	yes	7.44
E-MTAB-7249	no	14.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting DNAI3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988

Literature-anchored findings (GeneRIF, showing 2)

• These results indicate that WDR63 is a positive enhancer for stem cells from apical papilla osteogenic differentiation and suggest that activation of WDR63 signaling might improve tissue regeneration mediated by MSCs of dental origin. (PMID:25498833)
• A rare deletion in WDR63 in a case of encephalocele has been characterized. Functional study on zebrafish supports role of WDR63 deletion in abnormal neural development. (PMID:29285825)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	DNAI3	ENSDARG00000105093
mus_musculus	Dnai3	ENSMUSG00000043020
rattus_norvegicus	Dnai3	ENSRNOG00000014893

Paralogs (7): DYNC1I2 (ENSG00000077380), DYNC2I2 (ENSG00000119333), DNAI1 (ENSG00000122735), DYNC2I1 (ENSG00000126870), DNAI4 (ENSG00000152763), DYNC1I1 (ENSG00000158560), DNAI2 (ENSG00000171595)

Protein

Protein identifiers

Dynein axonemal intermediate chain 3 — Q8IWG1 (reviewed: Q8IWG1)

Alternative names: Testis development protein NYD-SP29, WD repeat-containing protein 63

All UniProt accessions (5): A0A140VJZ8, E9PLK2, E9PLW4, Q8IWG1, H0YEC9

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of cell migration, invasion, and metastasis downstream of p53/TP53, through inhibition of Arp2/3 complex-mediated actin polymerization. Via its association with the multisubunit axonemal dynein complex, is potentially involved in the regulation of cilia function. May play a role in osteogenesis of dental tissue-derived mesenchymal stem cells.

Subunit / interactions. Interacts with ACTR2; this interaction reduces binding of the Arp2/3 complex to the VCA domain of nucleation promoting factors. Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains. Found in a associated with the catalytic heavy chain DNAH2, the intermediate chain DNAI4, and the light chain DYNLT1.

Subcellular location. Cytoplasm.

Disease relevance. A rare heterozygous in-frame DNAI3 deletion encompassing exons 14-17 has been found in a fetus with encephalocele. Overexpression of human DNAI3 RNA lacking exons 14-17 in zebrafish embryos also results in similar brain malformations, suggesting that DNAI3 defects might be involved in encephalocele formation.

Induction. Up-regulated at the transcriptional level by TP53.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWG1-1	1	yes
Q8IWG1-2	2

RefSeq proteins (2): NP_001275492, NP_660155* (*=MANE)

Domains & families (InterPro)

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

UniProt features (14 total): repeat 4, sequence conflict 3, sequence variant 2, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWG1-F1	77.17	0.33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_INNER_DYNEIN_ARM_ASSEMBLY, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_CILIUM_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_ARP2_3_COMPLEX_MEDIATED_ACTIN_NUCLEATION

GO Biological Process (5): negative regulation of cell migration (GO:0030336), negative regulation of Arp2/3 complex-mediated actin nucleation (GO:0034316), inner dynein arm assembly (GO:0036159), positive regulation of osteoblast differentiation (GO:0045669), cilium movement involved in cell motility (GO:0060294)

GO Molecular Function (4): dynein light chain binding (GO:0045503), dynein heavy chain binding (GO:0045504), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), axonemal dynein complex (GO:0005858), inner dynein arm (GO:0036156)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
negative regulation of actin nucleation	1
axonemal dynein complex assembly	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
cilium movement	1
cell motility	1
cilium-dependent cell motility	1
protein-containing complex binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
axoneme	1
dynein complex	1
axonemal dynein complex	1

Protein interactions and networks

STRING

795 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAI3	DNAI4	Q5VTH9	805
DNAI3	DNAI1	Q9UI46	583
DNAI3	WDR37	Q9Y2I8	553
DNAI3	TMEM184A	Q6ZMB5	502
DNAI3	WDR47	O94967	497
DNAI3	WBP2NL	Q6ICG8	495
DNAI3	DRC9	Q9H095	490
DNAI3	LVRN	Q6Q4G3	479
DNAI3	NME8	Q8N427	478
DNAI3	GALNTL5	Q7Z4T8	469
DNAI3	DNAH10	Q8IVF4	454
DNAI3	ZFHX3	Q15911	452
DNAI3	ACSBG2	Q5FVE4	451
DNAI3	DRC11	Q86XH1	450
DNAI3	DNAI7	Q6TDU7	447

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DNAI3	GALM	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): GALM (Affinity Capture-MS), OGDHL (Affinity Capture-MS), EEA1 (Cross-Linking-MS (XL-MS)), WDR63 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KIZ8, A0A1L8GXY4, A0A571BF63, A0A8M9QN10, A2CEI4, A2RRP1, A4D1P6, A6H8T2, A9X1C6, B0FXQ5, B1WC10, B2KIQ4, B2RY71, B2RYI0, B7FF09, B7FF12, E9PYY5, F1QHZ6, Q1LXZ7, Q2HJE1, Q3UMY5, Q402B2, Q4V8G4, Q5R6T6, Q5RE88, Q5U1Z0, Q5VTH9, Q5XIZ9, Q5ZLL7, Q6DFC6, Q6DTM3, Q6GPB9, Q6P2C0, Q6TEN6, Q7TMQ7, Q7ZVR1, Q8BMG7, Q8BX17, Q8C147, Q8IWG1

Diamond homologs: A0A0G2KIZ8, B2RY71, Q8IWG1, Q95JP0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	115
Likely benign	9
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
428608	NC_000001.10:g.85569702_85585573del	Likely pathogenic

SpliceAI

5454 predictions. Top by Δscore:

Variant	Effect	Δscore
1:85029104:A:AC	donor_gain	1.0000
1:85029105:C:CC	donor_gain	1.0000
1:85032694:A:AC	donor_gain	1.0000
1:85032695:C:CC	donor_gain	1.0000
1:85032695:CAGT:C	donor_gain	1.0000
1:85032793:C:CC	acceptor_gain	1.0000
1:85032953:CACT:C	acceptor_gain	1.0000
1:85032955:CT:C	acceptor_gain	1.0000
1:85032962:A:C	acceptor_gain	1.0000
1:85034259:C:CT	acceptor_gain	1.0000
1:85041175:CAGCT:C	acceptor_gain	1.0000
1:85045249:T:C	donor_gain	1.0000
1:85045358:CATCT:C	acceptor_gain	1.0000
1:85045361:CT:C	acceptor_gain	1.0000
1:85045363:C:CC	acceptor_gain	1.0000
1:85045363:C:CG	acceptor_loss	1.0000
1:85045364:T:A	acceptor_loss	1.0000
1:85073052:A:AG	acceptor_gain	1.0000
1:85073053:G:GG	acceptor_gain	1.0000
1:85073053:GCT:G	acceptor_gain	1.0000
1:85073053:GCTA:G	acceptor_gain	1.0000
1:85081218:ACTTT:A	acceptor_gain	1.0000
1:85081222:T:A	acceptor_gain	1.0000
1:85081229:CCTA:C	acceptor_loss	1.0000
1:85081231:TA:T	acceptor_loss	1.0000
1:85081232:A:AG	acceptor_gain	1.0000
1:85081232:A:AT	acceptor_loss	1.0000
1:85081232:AG:A	acceptor_gain	1.0000
1:85081233:G:C	acceptor_loss	1.0000
1:85081233:G:GA	acceptor_gain	1.0000

AlphaMissense

5963 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:85097578:T:A	W425R	0.999
1:85097578:T:C	W425R	0.999
1:85108046:T:A	W523R	0.999
1:85108046:T:C	W523R	0.999
1:85126565:T:A	W723R	0.999
1:85126565:T:C	W723R	0.999
1:85094526:T:A	W382R	0.998
1:85094526:T:C	W382R	0.998
1:85098638:T:A	W487R	0.998
1:85098638:T:C	W487R	0.998
1:85104582:C:A	T513K	0.998
1:85108160:T:A	W561R	0.998
1:85108160:T:C	W561R	0.998
1:85126625:T:A	W743R	0.998
1:85126625:T:C	W743R	0.998
1:85093630:T:A	W344R	0.997
1:85093630:T:C	W344R	0.997
1:85096016:G:T	G420V	0.997
1:85104582:C:G	T513R	0.997
1:85126578:G:C	R727P	0.997
1:85094446:C:G	S355W	0.996
1:85095943:A:C	S396R	0.996
1:85095945:C:A	S396R	0.996
1:85095945:C:G	S396R	0.996
1:85096001:G:A	G415E	0.996
1:85104576:T:C	L511P	0.996
1:85121775:T:A	W648R	0.996
1:85121775:T:C	W648R	0.996
1:85124205:T:C	L689P	0.996
1:85130051:G:C	R824P	0.996

dbSNP variants (sampled 300 via entrez): RS1000028420 (1:85113522 G>A,T), RS1000050456 (1:85109930 A>C,G,T), RS1000064336 (1:85104670 G>T), RS1000076313 (1:85078262 C>T), RS1000080404 (1:85113109 T>C), RS1000182487 (1:85071735 C>T), RS1000229215 (1:85088807 T>C), RS1000243096 (1:85119689 T>C), RS1000273065 (1:85084488 A>ATATG), RS1000288840 (1:85096498 T>A), RS1000289928 (1:85065304 AC>A), RS1000335262 (1:85111761 G>C), RS1000342510 (1:85126458 C>T), RS1000376373 (1:85129875 G>A), RS1000408812 (1:85096239 A>T)

Disease associations

OMIM: gene MIM:617968 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): occipital encephalocele (MONDO:0017080)

Orphanet (1): Occipital encephalocele (Orphanet:268823)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006418_13	Progressive supranuclear palsy	6.000000e-07
GCST006418_4	Progressive supranuclear palsy	6.000000e-07
GCST006988_197	Blond vs. brown/black hair color	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Doxorubicin	affects expression, increases expression	3
Cisplatin	affects expression, affects cotreatment, increases expression	2
Formaldehyde	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
chloroacetaldehyde	decreases expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
monomethylpropion	increases expression	1
CGP 52608	increases reaction, affects binding	1
adefovir dipivoxil	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
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	increases expression	1
Clodronic Acid	decreases expression	1
Ifosfamide	decreases expression	1
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression	1
Lucanthone	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1

Clinical trials (associated diseases)

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