DNALI1

Summary

DNALI1 (dynein axonemal light intermediate chain 1, HGNC:14353) is a protein-coding gene on chromosome 1p34.3, encoding Axonemal dynein light intermediate polypeptide 1 (O14645). Involved in sperm flagellum assembly.

This gene is the human homolog of the Chlamydomonas inner dynein arm gene, p28. The precise function of this gene is not known, however, it is a potential candidate for immotile cilia syndrome (ICS). Ultrastructural defects of the inner dynein arms are seen in patients with ICS. Immotile mutant strains of Chlamydomonas, a biflagellated algae, exhibit similar defects.

Source: NCBI Gene 7802 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 83 (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 68 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_003462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14353
Approved symbol	DNALI1
Name	dynein axonemal light intermediate chain 1
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	P28, hp28, dJ423B22.5
Ensembl gene	ENSG00000163879
Ensembl biotype	protein_coding
OMIM	602135
Entrez	7802

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000296218, ENST00000466723, ENST00000467277, ENST00000490312, ENST00000497858, ENST00000652629, ENST00000852954, ENST00000918331, ENST00000970663

RefSeq mRNA: 1 — MANE Select: NM_003462 NM_003462

CCDS: CCDS420

Canonical transcript exons

ENST00000652629 — 6 exons

Exon	Start	End
ENSE00001215073	37559327	37559496
ENSE00001925656	37565026	37566857
ENSE00003490680	37562081	37562245
ENSE00003530202	37557603	37557748
ENSE00003564108	37561557	37561735
ENSE00003848650	37556940	37557075

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5202 / max 330.6453, expressed in 1157 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2211	5.8443	1055
2212	4.4134	956
2213	0.2625	145

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.40	gold quality
left testis	UBERON:0004533	97.65	gold quality
bronchial epithelial cell	CL:0002328	97.47	gold quality
right testis	UBERON:0004534	97.39	gold quality
epithelium of bronchus	UBERON:0002031	96.86	gold quality
bronchus	UBERON:0002185	96.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.00	gold quality
testis	UBERON:0000473	95.34	gold quality
adenohypophysis	UBERON:0002196	94.23	gold quality
pituitary gland	UBERON:0000007	92.97	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.66	gold quality
body of pancreas	UBERON:0001150	89.65	gold quality
caput epididymis	UBERON:0004358	89.38	gold quality
right lobe of thyroid gland	UBERON:0001119	88.66	gold quality
ventricular zone	UBERON:0003053	88.39	gold quality
left lobe of thyroid gland	UBERON:0001120	88.33	gold quality
thyroid gland	UBERON:0002046	87.92	gold quality
pancreas	UBERON:0001264	87.05	gold quality
islet of Langerhans	UBERON:0000006	87.02	gold quality
nasal cavity epithelium	UBERON:0005384	86.87	gold quality
gall bladder	UBERON:0002110	86.66	gold quality
metanephros cortex	UBERON:0010533	86.19	gold quality
body of stomach	UBERON:0001161	86.00	gold quality
epithelium of nasopharynx	UBERON:0001951	85.98	gold quality
nasopharynx	UBERON:0001728	85.97	gold quality
left ovary	UBERON:0002119	85.88	gold quality
right ovary	UBERON:0002118	85.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.60	gold quality
sperm	CL:0000019	84.22	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	938.99
E-CURD-114	yes	64.13
E-MTAB-10287	yes	26.84
E-HCAD-1	yes	25.99
E-ANND-3	yes	11.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXJ1

miRNA regulators (miRDB)

114 targeting DNALI1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-548AU-3P	99.70	68.22	1373

Literature-anchored findings (GeneRIF, showing 5)

• ADAP coprecipitates with dynein from activated Jurkat cells, and loss of ADAP prevents microtubule-organizing center (MTOC) translocation and the specific recruitment of dynein to the synapse. (PMID:16990435)
• Data indicate a putative toxofilin-binding protein dynein (DNALI1) by yeast two-hybrid assay. (PMID:29528377)
• DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath. (PMID:36792588)
• DNALI1 is a prognosis-related biomarker and correlates with immune infiltrates in low grade glioma. (PMID:37955080)
• DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome-Lysosome Fusion. (PMID:38348540)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnali1	ENSDARG00000069815
mus_musculus	Dnali1	ENSMUSG00000042707
rattus_norvegicus	Dnali1	ENSRNOG00000024957
drosophila_melanogaster	Dnali1	FBGN0037962
caenorhabditis_elegans		WBGENE00018307

Protein

Protein identifiers

Axonemal dynein light intermediate polypeptide 1 — O14645 (reviewed: O14645)

Alternative names: Inner dynein arm light chain, axonemal, hp28

All UniProt accessions (2): A0A499FIY3, O14645

UniProt curated annotations — full annotation on UniProt →

Function. Involved in sperm flagellum assembly.

Subunit / interactions. Interacts with CFAP45. Interacts with DYNC1H1.

Subcellular location. Cell projection. Cilium. Flagellum. Dynein axonemal particle. Cytoplasm.

Tissue specificity. Expressed in many tissues. A smaller 0.9 kb and a larger 2.5 kb transcripts were detected at the highest level in the testis, at medium levels in the prostate, heart, liver, lung and pancreas, at low levels in the ovary, skeletal muscle and small intestine. Not detected in spleen, colon epithelium, thymus or peripheral blood leukocytes. The 0.9 kb transcript is expressed at a 20-fold higher level than the 2.5 kb transcript in the testis. Expressed in spermatozoa and airway epithelial cells (at protein level).

Disease relevance. Spermatogenic failure 83 (SPGF83) [MIM:620354] An autosomal recessive male infertility disorder characterized by asthenoteratozoospermia. Patient sperm exhibit an asymmetric fibrous sheath of the flagella. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the inner dynein arm light chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14645-1	1	yes
O14645-2	2

RefSeq proteins (1): NP_003453* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019347	Axonemal_dynein_light_chain	Family

Pfam: PF10211

UniProt features (12 total): sequence conflict 3, region of interest 2, splice variant 2, sequence variant 2, chain 1, coiled-coil region 1, compositionally biased region 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-O14645-F1	85.32	0.75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 155 (showing top): YANG_BREAST_CANCER_ESR1_BULK_UP, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOBP_MALE_GAMETE_GENERATION, CHANDRAN_METASTASIS_DN, SMID_BREAST_CANCER_RELAPSE_IN_LIVER_DN, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SMID_BREAST_CANCER_LUMINAL_B_UP, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, MODULE_206, chr1p34, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, KEGG_HUNTINGTONS_DISEASE

GO Biological Process (1): sperm flagellum assembly (GO:0120316)

GO Molecular Function (2): dynein heavy chain binding (GO:0045504), protein binding (GO:0005515)

GO Cellular Component (18): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cilium (GO:0005929), axoneme (GO:0005930), microtubule cytoskeleton (GO:0015630), filopodium (GO:0030175), dynein complex (GO:0030286), motile cilium (GO:0031514), sperm flagellum (GO:0036126), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), ciliary base (GO:0097546), 9+2 motile cilium (GO:0097729), dynein axonemal particle (GO:0120293), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	9
sperm flagellum	3
cytoskeleton	2
cilium	2
developmental process involved in reproduction	1
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
protein binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule	1
ciliary plasm	1
actin-based cell projection	1
microtubule associated complex	1
catalytic complex	1
9+2 motile cilium	1
spindle	1
ciliary transition zone	1
ciliary transition fiber	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNALI1	DNAI2	Q9GZS0	983
DNALI1	DNAH5	Q8TE73	975
DNALI1	DNAAF1	Q8NEP3	966
DNALI1	DNAI1	Q9UI46	825
DNALI1	RSPH4A	Q5TD94	760
DNALI1	CCDC39	Q9UFE4	755
DNALI1	DRC4	O95995	734
DNALI1	DNAAF3	Q8N9W5	732
DNALI1	ZMYND10	O75800	724
DNALI1	DNAAF11	Q86X45	717
DNALI1	CCDC40	Q4G0X9	713
DNALI1	DNAH9	Q9NYC9	701
DNALI1	RSPH9	Q9H1X1	693
DNALI1	ODAD1	Q96M63	688
DNALI1	DNAAF6	Q9NQM4	666

IntAct

262 interactions, top by confidence:

A	B	Type	Score
DNALI1	HTT	psi-mi:“MI:0915”(physical association)	0.740
HTT	DNALI1	psi-mi:“MI:0915”(physical association)	0.740
DNALI1	EIF3K	psi-mi:“MI:0915”(physical association)	0.730
DNALI1	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	DNALI1	psi-mi:“MI:0915”(physical association)	0.560
DNALI1		psi-mi:“MI:0915”(physical association)	0.560
DNALI1	ALAS1	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	ANXA8	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	ATP6V1B1	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	BCAT1	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	KLF5	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	DXO	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	DPYS	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	FYN	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	DNALI1	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	IFI35	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	MT2A	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	RAP1GAP	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	RGR	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (20): DNALI1 (Two-hybrid), GSN (Affinity Capture-MS), PFN2 (Affinity Capture-MS), EIF3K (Affinity Capture-MS), SESTD1 (Affinity Capture-MS), ARPC4 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), DNM2 (Affinity Capture-MS), ACTR3 (Affinity Capture-MS), DNALI1 (Two-hybrid), DNALI1 (Two-hybrid), DNALI1 (Two-hybrid), HIST1H4A (Cross-Linking-MS (XL-MS)), PRPF40A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0AUQ6, A2BE76, O14645, O18973, O35427, O35473, O55003, O88447, O88597, P50503, Q05B58, Q12983, Q13901, Q14457, Q14AM7, Q14CZ0, Q28HY5, Q32KN2, Q32PE4, Q4A1L3, Q4A1L4, Q4A1L5, Q4R3K5, Q4R8N2, Q4RLT3, Q52LA3, Q5JSJ4, Q5NVP8, Q5R878, Q5RBU4, Q5TKA1, Q5ZHS3, Q5ZJQ3, Q68FJ8, Q6DKA1, Q6GMH0, Q6GP52, Q6PAX8, Q6X4M3, Q7TSU0

Diamond homologs: O14645, Q26630, Q39604, Q4FZV3, Q4R3K5, Q6GN86, Q8BVN8, Q9VGG6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXJ1	“up-regulates quantity by expression”	DNALI1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	50
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2500164	NM_003462.5(DNALI1):c.666_669del (p.Ser222fs)	Pathogenic
3338308	DNALI1, IVS3, G-A, -1	Pathogenic
4849363	NM_003462.5(DNALI1):c.568G>T (p.Glu190Ter)	Likely pathogenic

SpliceAI

847 predictions. Top by Δscore:

Variant	Effect	Δscore
1:37557072:CAAG:C	donor_loss	1.0000
1:37557077:T:A	donor_loss	1.0000
1:37561549:A:AG	acceptor_gain	1.0000
1:37561549:ATT:A	acceptor_gain	1.0000
1:37561733:A:T	donor_gain	1.0000
1:37561536:AT:A	acceptor_gain	0.9900
1:37561537:T:TA	acceptor_gain	0.9900
1:37561549:ATTG:A	acceptor_gain	0.9900
1:37561550:T:G	acceptor_gain	0.9900
1:37561551:T:TA	acceptor_gain	0.9900
1:37561556:GATGA:G	acceptor_gain	0.9900
1:37561690:G:GT	donor_gain	0.9900
1:37561703:GC:G	donor_gain	0.9900
1:37561714:G:GT	donor_gain	0.9900
1:37561714:G:T	donor_gain	0.9900
1:37561731:GGAAA:G	donor_gain	0.9900
1:37561732:GAAAG:G	donor_gain	0.9900
1:37561736:G:GG	donor_gain	0.9900
1:37562076:CTCA:C	acceptor_loss	0.9900
1:37562077:TCAG:T	acceptor_loss	0.9900
1:37562077:TCAGA:T	acceptor_gain	0.9900
1:37562078:CA:C	acceptor_loss	0.9900
1:37562078:CAGAT:C	acceptor_gain	0.9900
1:37562079:A:T	acceptor_gain	0.9900
1:37562079:AGAT:A	acceptor_loss	0.9900
1:37562080:G:T	acceptor_gain	0.9900
1:37562080:GA:G	acceptor_gain	0.9900
1:37562080:GATC:G	acceptor_gain	0.9900
1:37562243:AAGG:A	donor_loss	0.9900
1:37562245:GGTAA:G	donor_loss	0.9900

AlphaMissense

1673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:37559460:T:C	C121R	1.000
1:37561598:G:A	G147R	1.000
1:37561598:G:C	G147R	1.000
1:37561598:G:T	G147W	1.000
1:37561599:G:A	G147E	1.000
1:37561679:T:C	F174L	1.000
1:37561681:T:A	F174L	1.000
1:37561681:T:G	F174L	1.000
1:37562241:T:C	L246P	1.000
1:37559416:T:C	L106S	0.999
1:37559428:T:C	L110P	0.999
1:37559443:C:A	A115D	0.999
1:37559454:G:C	G119R	0.999
1:37559455:G:A	G119D	0.999
1:37559461:G:A	C121Y	0.999
1:37559462:C:G	C121W	0.999
1:37559469:C:A	R124S	0.999
1:37559479:T:C	L127P	0.999
1:37561569:G:C	R137P	0.999
1:37561599:G:T	G147V	0.999
1:37561608:T:C	L150P	0.999
1:37561620:G:C	R154P	0.999
1:37561659:T:C	L167P	0.999
1:37561670:A:C	S171R	0.999
1:37561672:C:A	S171R	0.999
1:37561672:C:G	S171R	0.999
1:37561683:G:A	G175D	0.999
1:37561689:G:T	R177M	0.999
1:37561690:G:C	R177S	0.999
1:37561690:G:T	R177S	0.999

dbSNP variants (sampled 300 via entrez): RS1000182103 (1:37560431 A>G), RS1000212313 (1:37562552 G>A), RS1000276192 (1:37560329 G>A), RS1000288291 (1:37566749 A>C), RS1000732591 (1:37564531 T>A,C), RS1000808548 (1:37566143 C>A), RS1001198685 (1:37566358 C>G), RS1001253104 (1:37559399 G>A,C), RS1001368891 (1:37559780 G>A,T), RS1001518095 (1:37565368 A>G), RS1001968572 (1:37565791 G>C), RS1002254944 (1:37563879 T>G), RS1003023001 (1:37557990 A>T), RS1003275578 (1:37564624 G>A), RS1003337339 (1:37556852 C>A,G,T)

Disease associations

OMIM: gene MIM:602135 | disease phenotypes: MIM:620354

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 83	Limited	Unknown

Mondo (1): spermatogenic failure 83 (MONDO:0957250)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0034011	Reduced progressive sperm motility
HP:0034947	Altered location of the longitudinal column in the fibrous sheath

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002115_4	Axial length	4.000000e-13
GCST003476_2	Eyebrow thickness	7.000000e-06
GCST005580_250	Intraocular pressure	1.000000e-10
GCST005580_279	Intraocular pressure	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
sodium arsenite	decreases expression	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Lead	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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