DNAL4

Summary

DNAL4 (dynein axonemal light chain 4, HGNC:2955) is a protein-coding gene on chromosome 22q13.1, encoding Dynein axonemal light chain 4 (O96015). Force generating protein of respiratory cilia.

This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella.

Source: NCBI Gene 10126 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial congenital mirror movements (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 19 total — 1 pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_005740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2955
Approved symbol	DNAL4
Name	dynein axonemal light chain 4
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ327J16, PIG27
Ensembl gene	ENSG00000100246
Ensembl biotype	protein_coding
OMIM	610565
Entrez	10126

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000216068, ENST00000406199, ENST00000475512, ENST00000486019, ENST00000906779, ENST00000906780, ENST00000906781, ENST00000916101, ENST00000916102, ENST00000964351, ENST00000964352, ENST00000964353, ENST00000964354

RefSeq mRNA: 1 — MANE Select: NM_005740 NM_005740

CCDS: CCDS13979

Canonical transcript exons

ENST00000216068 — 4 exons

Exon	Start	End
ENSE00000654559	38780926	38781009
ENSE00001048120	38778508	38779613
ENSE00001048126	38782663	38782870
ENSE00001829474	38794068	38794143

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 95.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2949 / max 86.1217, expressed in 96 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194231	16.2463	1804
194229	0.2949	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.11	gold quality
right testis	UBERON:0004534	94.90	gold quality
right uterine tube	UBERON:0001302	94.14	gold quality
testis	UBERON:0000473	92.96	gold quality
adenohypophysis	UBERON:0002196	90.38	gold quality
oocyte	CL:0000023	90.16	gold quality
cingulate cortex	UBERON:0003027	89.70	gold quality
anterior cingulate cortex	UBERON:0009835	89.69	gold quality
right lobe of thyroid gland	UBERON:0001119	89.60	gold quality
right frontal lobe	UBERON:0002810	89.33	gold quality
amygdala	UBERON:0001876	89.17	gold quality
nucleus accumbens	UBERON:0001882	89.10	gold quality
pituitary gland	UBERON:0000007	88.98	gold quality
left lobe of thyroid gland	UBERON:0001120	88.96	gold quality
prefrontal cortex	UBERON:0000451	88.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.06	gold quality
thyroid gland	UBERON:0002046	87.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.69	gold quality
caudate nucleus	UBERON:0001873	87.63	gold quality
mucosa of transverse colon	UBERON:0004991	87.39	gold quality
body of pancreas	UBERON:0001150	87.11	gold quality
putamen	UBERON:0001874	87.06	gold quality
lower esophagus mucosa	UBERON:0035834	87.01	gold quality
metanephros cortex	UBERON:0010533	86.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.31	gold quality
right adrenal gland	UBERON:0001233	86.29	gold quality
stromal cell of endometrium	CL:0002255	86.21	gold quality
right adrenal gland cortex	UBERON:0035827	86.14	gold quality
secondary oocyte	CL:0000655	86.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting DNAL4, 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-188-3P	100.00	68.76	1240
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4534	99.99	66.58	1907
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-1250-3P	99.96	70.04	4038
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-410-3P	99.27	69.98	2457

Literature-anchored findings (GeneRIF, showing 2)

• DNAL4 may play a role in the cytoplasmic dynein complex for netrin-1-directed retrograde transport, and in commissural neurons of the corpus callosum in particular. This could lead to faulty cross-brain wiring, resulting in Mirror movements (MRMV). (PMID:25098561)
• No mutation in DNAL4 in Congenital mirror movements. (PMID:25236653)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnal4a	ENSDARG00000031116
danio_rerio	dnal4b	ENSDARG00000088841
mus_musculus	Dnal4	ENSMUSG00000022420
rattus_norvegicus	Dnal4	ENSRNOG00000015583
rattus_norvegicus	Dnal4-ps1	ENSRNOG00000067902
drosophila_melanogaster	CG8407	FBGN0033687

Protein

Protein identifiers

Dynein axonemal light chain 4 — O96015 (reviewed: O96015)

All UniProt accessions (2): O96015, B0QXZ5

UniProt curated annotations — full annotation on UniProt →

Function. Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity.

Subunit / interactions. Consists of at least two heavy chains and a number of intermediate and light chains.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Disease relevance. Mirror movements 3 (MRMV3) [MIM:616059] A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the dynein light chain family.

RefSeq proteins (1): NP_005731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001372	Dynein_light_chain_typ-1/2	Family
IPR037177	DLC_sf	Homologous_superfamily

Pfam: PF01221

UniProt features (3 total): chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O96015-F1	90.49	0.79

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-177504	Retrograde neurotrophin signalling

MSigDB gene sets: 131 (showing top): REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, SCIBETTA_KDM5B_TARGETS_UP, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, KEGG_HUNTINGTONS_DISEASE, AGGAGTG_MIR483, CYTAGCAAY_UNKNOWN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, AIYAR_COBRA1_TARGETS_UP, GOCC_CYTOPLASMIC_REGION, chr22q13, GOCC_DYNEIN_COMPLEX, RFX1_01, GOCC_CILIUM, GOMF_MICROTUBULE_MOTOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (2): microtubule-based movement (GO:0007018), microtubule-based process (GO:0007017)

GO Molecular Function (3): microtubule motor activity (GO:0003777), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (8): microtubule (GO:0005874), plasma membrane (GO:0005886), axoneme (GO:0005930), dynein complex (GO:0030286), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by NTRK1 (TRKA)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule-based process	1
cellular process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
protein binding	1
binding	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule associated complex	1
catalytic complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAL4	HOXA4	Q00056	712
DNAL4	DNAI2	Q9GZS0	565
DNAL4	DNAH9	Q9NYC9	547
DNAL4	DNALI1	O14645	543
DNAL4	DNAI1	Q9UI46	535
DNAL4	DYNLT1	P63172	521
DNAL4	DYNLL2	Q96FJ2	516
DNAL4	DYNLRB1	Q9NP97	494
DNAL4	NUP98	P52948	491
DNAL4	DNAH3	Q8TD57	491
DNAL4	DNAAF8	Q8IYS4	488
DNAL4	DNAL1	Q4LDG9	479
DNAL4	DNAH7	Q8WXX0	479
DNAL4	DNAH10	Q8IVF4	478
DNAL4	DYNLT3	P51808	476

IntAct

74 interactions, top by confidence:

A	B	Type	Score
DNAL4	DYNLL2	psi-mi:“MI:0915”(physical association)	0.800
DNAL4	FHL5	psi-mi:“MI:0915”(physical association)	0.800
DYNLL2	DNAL4	psi-mi:“MI:0915”(physical association)	0.800
FHL5	DNAL4	psi-mi:“MI:0915”(physical association)	0.800
CAMK2D	DNAL4	psi-mi:“MI:0915”(physical association)	0.740
DNAL4	CAMK2D	psi-mi:“MI:0915”(physical association)	0.740
DNAL4	DYNLL1	psi-mi:“MI:0915”(physical association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
GNA14	DNAL4	psi-mi:“MI:0915”(physical association)	0.560
	DNAL4	psi-mi:“MI:0915”(physical association)	0.560
DNAL4	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	DNAL4	psi-mi:“MI:0915”(physical association)	0.560
DNAL4	GNA14	psi-mi:“MI:0915”(physical association)	0.560
DNAL4		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (48): DNAL4 (Two-hybrid), DNAL4 (Two-hybrid), TRIM54 (Two-hybrid), DYNLL2 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), DYNLL2 (Two-hybrid), DNAL4 (Two-hybrid), FHL5 (Two-hybrid), DNAL4 (Two-hybrid), DNAL4 (Two-hybrid), DNAL4 (Two-hybrid), CHIC2 (Two-hybrid), FHL5 (Two-hybrid), NUDT22 (Two-hybrid)

ESM2 similar proteins: A2VE01, A4F4L4, O70133, O88761, O94973, O96015, P17427, P18484, P19803, P35615, P38024, P48444, P52565, P53619, P62495, P62496, P62497, P62498, Q08211, Q0VCK5, Q0VCX5, Q1W375, Q28141, Q32KN5, Q3TXS7, Q4R4J0, Q4R7R3, Q5F418, Q5R4C7, Q5R5S4, Q5R874, Q5RA77, Q5U2Q7, Q5XI73, Q5XJY5, Q5ZJL4, Q5ZL57, Q66H80, Q68FK8, Q6NRT5

Diamond homologs: A4F4L4, O02414, O94111, O96015, O96860, P61273, P61285, P63167, P63168, P63169, P63170, Q02647, Q22799, Q24117, Q32KN5, Q39580, Q3MHR3, Q6BZF8, Q6CWX4, Q6FUJ0, Q759T0, Q78P75, Q86A88, Q94758, Q96FJ2, Q9D0M5, Q9DCM4, Q9UR05, Q21557, Q39579, Q94748

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
157500	NM_005740.3(DNAL4):c.153+2T>C	Pathogenic

SpliceAI

743 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38779610:CGCT:C	acceptor_gain	1.0000
22:38781007:GTG:G	acceptor_gain	1.0000
22:38781008:TG:T	acceptor_gain	1.0000
22:38781008:TGC:T	acceptor_loss	1.0000
22:38781009:GCT:G	acceptor_loss	1.0000
22:38781010:C:CC	acceptor_gain	1.0000
22:38781010:CTAG:C	acceptor_loss	1.0000
22:38781011:T:C	acceptor_loss	1.0000
22:38794062:CCTCA:C	donor_loss	1.0000
22:38794063:CTCA:C	donor_loss	1.0000
22:38794064:TCAC:T	donor_loss	1.0000
22:38794065:CA:C	donor_loss	1.0000
22:38794067:CCTG:C	donor_gain	1.0000
22:38779460:T:TA	donor_gain	0.9900
22:38779609:GCGCT:G	acceptor_gain	0.9900
22:38779610:CGCTC:C	acceptor_gain	0.9900
22:38779612:CT:C	acceptor_gain	0.9900
22:38779613:TC:T	acceptor_loss	0.9900
22:38779614:C:A	acceptor_gain	0.9900
22:38779614:C:CA	acceptor_loss	0.9900
22:38779614:C:CC	acceptor_gain	0.9900
22:38779615:T:C	acceptor_loss	0.9900
22:38780924:ACCT:A	donor_loss	0.9900
22:38780925:CCTC:C	donor_loss	0.9900
22:38781003:CCGAG:C	acceptor_gain	0.9900
22:38781005:GAGTG:G	acceptor_gain	0.9900
22:38781006:AGTG:A	acceptor_gain	0.9900
22:38781022:C:CT	acceptor_gain	0.9900
22:38781023:A:T	acceptor_gain	0.9900
22:38782661:AC:A	donor_gain	0.9900

AlphaMissense

700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38779562:A:G	W69R	1.000
22:38779562:A:T	W69R	1.000
22:38779593:T:A	K58N	1.000
22:38779593:T:G	K58N	1.000
22:38779463:A:G	W102R	0.999
22:38779463:A:T	W102R	0.999
22:38779474:G:T	A98D	0.999
22:38779536:A:C	F77L	0.999
22:38779536:A:T	F77L	0.999
22:38779538:A:G	F77L	0.999
22:38779546:C:A	G74V	0.999
22:38779546:C:T	G74D	0.999
22:38779547:C:G	G74R	0.999
22:38779594:T:A	K58I	0.999
22:38779606:G:T	A54D	0.999
22:38779609:G:T	A53D	0.999
22:38780954:G:T	A42D	0.999
22:38780955:C:G	A42P	0.999
22:38780962:A:C	C39W	0.999
22:38780963:C:T	C39Y	0.999
22:38780964:A:G	C39R	0.999
22:38779461:C:A	W102C	0.998
22:38779461:C:G	W102C	0.998
22:38779465:A:T	V101D	0.998
22:38779467:G:C	C100W	0.998
22:38779501:A:G	L89P	0.998
22:38779504:A:G	L88P	0.998
22:38779555:A:T	V71E	0.998
22:38779560:C:A	W69C	0.998
22:38779560:C:G	W69C	0.998

dbSNP variants (sampled 300 via entrez): RS1000047956 (22:38795673 G>A), RS1000163071 (22:38778388 G>A), RS1000272503 (22:38793943 A>G), RS1000368451 (22:38783639 T>C), RS1000374361 (22:38789243 G>A), RS1000625161 (22:38795462 A>C,G), RS1000820138 (22:38784909 G>A), RS1000901487 (22:38779472 C>T), RS1001016717 (22:38795236 CAAGAGT>C), RS1001153034 (22:38789752 A>G), RS1001273756 (22:38784324 C>T), RS1001387719 (22:38784666 A>G), RS1001431582 (22:38789636 T>G), RS1001545878 (22:38781491 C>T), RS1001680670 (22:38792488 G>C)

Disease associations

OMIM: gene MIM:610565 | disease phenotypes: MIM:616059

GenCC curated gene-disease

Disease	Classification	Inheritance
familial congenital mirror movements	Supportive	Autosomal dominant
mirror movements 3	Limited	Unknown

Mondo (2): mirror movements 3 (MONDO:0014478), familial congenital mirror movements (MONDO:0016558)

Orphanet (1): Familial congenital mirror movements (Orphanet:238722)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0001256	Mild intellectual disability
HP:0001274	Agenesis of corpus callosum
HP:0001328	Specific learning disability
HP:0001335	Bimanual synkinesia
HP:0001696	Situs inversus totalis
HP:0002312	Clumsiness
HP:0002492	Abnormal corticospinal tract morphology
HP:0002949	Fused cervical vertebrae
HP:0003326	Myalgia
HP:0003388	Easy fatigability
HP:0007010	Poor fine motor coordination
HP:0025101	Dysgenesis of the hippocampus
HP:0100021	Cerebral palsy
HP:0100022	Abnormality of movement

GWAS associations

0 associations (top):

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
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02073604	Not specified	COMPLETED	Role of the SMA During Unimanual and Bimanual Movements Preparation: the Mirror Movements Paradigm