DNAI4

Summary

DNAI4 (dynein axonemal intermediate chain 4, HGNC:26252) is a protein-coding gene on chromosome 1p31.3, encoding Dynein axonemal intermediate chain 4 (Q5VTH9). Plays a critical role in the assembly of axonemal dynein complex, thereby playing a role in ciliary motility.

Predicted to enable dynein heavy chain binding activity and dynein light chain binding activity. Predicted to be involved in axonemal dynein complex assembly and cilium movement. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in axoneme; dynein axonemal particle; and motile cilium. Predicted to be part of axonemal dynein complex.

Source: NCBI Gene 79819 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 163 total — 1 pathogenic
• MANE Select transcript: NM_024763

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26252
Approved symbol	DNAI4
Name	dynein axonemal intermediate chain 4
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	DIC4, FLJ23129
Ensembl gene	ENSG00000152763
Ensembl biotype	protein_coding
OMIM	619156
Entrez	79819

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000371022, ENST00000371023, ENST00000371026, ENST00000464352, ENST00000469450, ENST00000474506, ENST00000488333, ENST00000491297, ENST00000493572, ENST00000531552, ENST00000531980, ENST00000532629, ENST00000908561, ENST00000908562, ENST00000908563, ENST00000908564, ENST00000908565, ENST00000908566, ENST00000908567, ENST00000959923

RefSeq mRNA: 2 — MANE Select: NM_024763 NM_024763, NM_207014

CCDS: CCDS44157, CCDS635

Canonical transcript exons

ENST00000371026 — 17 exons

Exon	Start	End
ENSE00001006971	66835626	66835777
ENSE00001864720	66812885	66814180
ENSE00003496086	66847484	66847678
ENSE00003541035	66862147	66862302
ENSE00003545197	66837710	66837796
ENSE00003552009	66822361	66822517
ENSE00003556170	66905201	66905375
ENSE00003570041	66891154	66891266
ENSE00003570474	66874781	66874937
ENSE00003572338	66871370	66871509
ENSE00003577230	66893229	66893413
ENSE00003608937	66826820	66827046
ENSE00003616445	66840469	66840671
ENSE00003635678	66833991	66834148
ENSE00003670331	66833585	66833706
ENSE00003675657	66924662	66924856
ENSE00003684695	66827812	66827910

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2491 / max 75.2944, expressed in 1360 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12732	3.1401	1335
12733	0.1090	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.43	gold quality
epithelium of bronchus	UBERON:0002031	97.04	gold quality
sperm	CL:0000019	96.16	gold quality
bronchus	UBERON:0002185	96.00	gold quality
right uterine tube	UBERON:0001302	94.72	gold quality
calcaneal tendon	UBERON:0003701	93.75	gold quality
male germ cell	CL:0000015	92.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.11	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.70	gold quality
left testis	UBERON:0004533	86.56	gold quality
right testis	UBERON:0004534	86.06	gold quality
epithelium of nasopharynx	UBERON:0001951	85.90	gold quality
testis	UBERON:0000473	85.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.70	gold quality
caput epididymis	UBERON:0004358	83.22	gold quality
mucosa of transverse colon	UBERON:0004991	81.63	gold quality
buccal mucosa cell	CL:0002336	81.61	gold quality
nasal cavity epithelium	UBERON:0005384	81.36	gold quality
tendon	UBERON:0000043	80.51	gold quality
adrenal tissue	UBERON:0018303	79.84	gold quality
rectum	UBERON:0001052	77.86	gold quality
corpus callosum	UBERON:0002336	76.53	gold quality
left lobe of thyroid gland	UBERON:0001120	76.18	gold quality
right lobe of thyroid gland	UBERON:0001119	75.95	gold quality
sural nerve	UBERON:0015488	75.89	gold quality
thyroid gland	UBERON:0002046	75.88	gold quality
endocervix	UBERON:0000458	75.37	gold quality
nasal cavity mucosa	UBERON:0001826	75.31	gold quality
fallopian tube	UBERON:0003889	75.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	60.82
E-ANND-3	yes	7.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting DNAI4, 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-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-12129	99.72	67.45	1311

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnai4	ENSDARG00000044400
mus_musculus	Dnai4	ENSMUSG00000035126
rattus_norvegicus	Dnai4	ENSRNOG00000006999
drosophila_melanogaster	CG13930	FBGN0035256
drosophila_melanogaster	Dic61B	FBGN0263988

Paralogs (7): DYNC1I2 (ENSG00000077380), DYNC2I2 (ENSG00000119333), DNAI1 (ENSG00000122735), DYNC2I1 (ENSG00000126870), DYNC1I1 (ENSG00000158560), DNAI3 (ENSG00000162643), DNAI2 (ENSG00000171595)

Protein

Protein identifiers

Dynein axonemal intermediate chain 4 — Q5VTH9 (reviewed: Q5VTH9)

Alternative names: WD repeat-containing protein 78

All UniProt accessions (9): Q5VTH9, E9PQT5, H0YCX1, H0YD49, H0YD58, H0YDI6, H0YEH4, H0YES1, Q5TAD8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in the assembly of axonemal dynein complex, thereby playing a role in ciliary motility.

Subunit / interactions. Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains. Associated with axonemal dynein subunits such as, DNAH2, DNAI3, and DYNLT1. Interacts with DYNLT1.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme. Cilium axoneme. Dynein axonemal particle.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VTH9-1	1	yes
Q5VTH9-2	2
Q5VTH9-3	3

RefSeq proteins (2): NP_079039, NP_996897 (=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

Pfam: PF00400

UniProt features (18 total): repeat 6, splice variant 4, sequence variant 3, compositionally biased region 2, region of interest 2, chain 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-Q5VTH9-F1	68.48	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 164 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, CMYB_01, MAZ_Q6, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, HNF1_C, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CDPCR3HD_01, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (3): hematopoietic progenitor cell differentiation (GO:0002244), cilium movement (GO:0003341), axonemal dynein complex assembly (GO:0070286)

GO Molecular Function (3): dynein light chain binding (GO:0045503), dynein heavy chain binding (GO:0045504), protein binding (GO:0005515)

GO Cellular Component (8): axonemal dynein complex (GO:0005858), axoneme (GO:0005930), motile cilium (GO:0031514), dynein axonemal particle (GO:0120293), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
intracellular membraneless organelle	2
hemopoiesis	1
cell differentiation	1
microtubule-based movement	1
axoneme assembly	1
protein-containing complex assembly	1
binding	1
axoneme	1
dynein complex	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cilium	1
cytoplasm	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

913 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAI4	DNAI3	Q8IWG1	805
DNAI4	DYNLT5	Q8N7M0	611
DNAI4	DNAAF1	Q8NEP3	570
DNAI4	SPAG1	Q07617	569
DNAI4	RUVBL1	P82276	568
DNAI4	CFAP251	Q8TBY9	530
DNAI4	WDR47	O94967	492
DNAI4	DNAH10	Q8IVF4	480
DNAI4	DNAH9	Q9NYC9	479
DNAI4	CFAP43	Q8NDM7	471
DNAI4	IFT140	Q96RY7	469
DNAI4	DNAH6	Q9C0G6	464
DNAI4	WDR37	Q9Y2I8	461
DNAI4	DNAH2	Q9P225	455
DNAI4	CFAP52	Q8N1V2	453

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): WDR78 (Protein-RNA), WDR78 (Affinity Capture-MS), ARPC4 (Cross-Linking-MS (XL-MS)), WDR78 (Affinity Capture-RNA)

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: E9PYY5, F1QHZ6, Q16959, Q39578, Q4V8G4, Q5VTH9, Q6GPB9, Q32KS2, Q5XIL8, Q8C0M8, Q9UI46, Q54ED4, Q55C80, Q4QR85, Q5E9I7, Q5RBZ2, Q6NUD0, Q99J09, Q9BQA1, Q9Y7T2, O22607, Q9FFA7, A1CGS0, A2QHM1, A3LNW3, A4REK3, A5DHD9, A5DXE2, A6RT32, A7EZJ5, A7RWD2, A8WVD2, A8XJ40, B0XAF3, B9WD30, C4YPI7, C5MJE8, G0SA60, O45933, O64740

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	130
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425382	NC_000001.10:g.(?61548464)(67861772_?)del	Pathogenic

SpliceAI

2556 predictions. Top by Δscore:

Variant	Effect	Δscore
1:66826813:AACTT:A	donor_loss	1.0000
1:66826814:ACTT:A	donor_loss	1.0000
1:66826815:CTT:C	donor_loss	1.0000
1:66826816:TTA:T	donor_loss	1.0000
1:66826817:TACGT:T	donor_loss	1.0000
1:66826818:A:AC	donor_gain	1.0000
1:66826818:A:T	donor_loss	1.0000
1:66826818:ACGTG:A	donor_gain	1.0000
1:66826819:C:CA	donor_gain	1.0000
1:66826819:CGT:C	donor_gain	1.0000
1:66826819:CGTG:C	donor_gain	1.0000
1:66826819:CGTGC:C	donor_gain	1.0000
1:66833580:TTTAC:T	donor_loss	1.0000
1:66833581:TTAC:T	donor_loss	1.0000
1:66833582:TAC:T	donor_loss	1.0000
1:66833609:T:A	donor_gain	1.0000
1:66833702:CAAAT:C	acceptor_gain	1.0000
1:66833703:AAAT:A	acceptor_gain	1.0000
1:66833704:AAT:A	acceptor_gain	1.0000
1:66833705:AT:A	acceptor_gain	1.0000
1:66833706:TC:T	acceptor_loss	1.0000
1:66833707:C:CA	acceptor_loss	1.0000
1:66833707:C:CC	acceptor_gain	1.0000
1:66833709:G:C	acceptor_gain	1.0000
1:66833711:A:C	acceptor_gain	1.0000
1:66833712:T:TC	acceptor_gain	1.0000
1:66833713:T:C	acceptor_gain	1.0000
1:66833713:T:TC	acceptor_gain	1.0000
1:66834147:CA:C	acceptor_gain	1.0000
1:66835778:C:CC	acceptor_gain	1.0000

AlphaMissense

5578 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:66826993:G:C	S722R	1.000
1:66826993:G:T	S722R	1.000
1:66826995:T:G	S722R	1.000
1:66826896:A:G	W755R	0.999
1:66826896:A:T	W755R	0.999
1:66827888:C:T	G679D	0.999
1:66837730:A:G	W521R	0.999
1:66837730:A:T	W521R	0.999
1:66826839:A:G	W774R	0.998
1:66826839:A:T	W774R	0.998
1:66826965:A:G	W732R	0.998
1:66826965:A:T	W732R	0.998
1:66827000:A:G	F720S	0.998
1:66822428:C:T	G810E	0.997
1:66826871:A:G	F763S	0.997
1:66826988:G:A	S724F	0.997
1:66826989:A:G	S724P	0.997
1:66827039:A:T	V707E	0.997
1:66827889:C:G	G679R	0.997
1:66840537:A:G	W476R	0.997
1:66840537:A:T	W476R	0.997
1:66822410:A:T	V816D	0.996
1:66822429:C:G	G810R	0.996
1:66822429:C:T	G810R	0.996
1:66826837:C:A	W774C	0.996
1:66826837:C:G	W774C	0.996
1:66826868:G:T	A764E	0.996
1:66827898:A:C	Y676D	0.996
1:66834021:A:G	W621R	0.996
1:66834021:A:T	W621R	0.996

dbSNP variants (sampled 300 via entrez): RS1000000574 (1:66884939 G>A), RS1000006761 (1:66913948 C>A,T), RS1000051306 (1:66884653 G>C), RS1000107998 (1:66818922 A>G,T), RS1000113140 (1:66920650 C>T), RS1000149082 (1:66859145 C>G,T), RS1000156512 (1:66862855 T>G), RS1000197917 (1:66832138 C>A), RS1000204242 (1:66849890 GA>G,GAA), RS1000229669 (1:66921163 T>C), RS1000249567 (1:66825165 T>C), RS1000279515 (1:66863101 C>A), RS1000327015 (1:66838635 T>G), RS1000373847 (1:66852356 A>G), RS1000387653 (1:66812785 CA>C,CAA)

Disease associations

OMIM: gene MIM:619156 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004131_16	Inflammatory bowel disease	5.000000e-111
GCST004132_7	Crohn’s disease	6.000000e-93
GCST004133_2	Ulcerative colitis	4.000000e-41
GCST008362_138	Birth weight	5.000000e-08
GCST90002389_56	Lymphocyte percentage of white cells	1.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression, decreases methylation	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Smoke	increases abundance, increases expression	1
Gold Compounds	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery