DYNLL2

Summary

DYNLL2 (dynein light chain LC8-type 2, HGNC:24596) is a protein-coding gene on chromosome 17q22, encoding Dynein light chain 2, cytoplasmic (Q96FJ2). 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.

Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in several processes, including flagellated sperm motility; intraciliary retrograde transport; and positive regulation of mitotic cell cycle spindle assembly checkpoint. Located in 9+0 non-motile cilium and centrosome. Is active in glutamatergic synapse and postsynapse.

Source: NCBI Gene 140735 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 7 total
• GTEx eGene: eQTL in 36 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.96 (loss-of-function intolerant), LOEUF 0.46 (moderately constrained)
• MANE Select transcript: NM_080677
• Interaction hub: 2,556 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24596
Approved symbol	DYNLL2
Name	dynein light chain LC8-type 2
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	MGC17810, Dlc2, DNCL1B, RSPH22
Ensembl gene	ENSG00000264364
Ensembl biotype	protein_coding
OMIM	608942
Entrez	140735

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

MANE Select: ENST00000579991

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000579991, ENST00000908491, ENST00000908492, ENST00000908493, ENST00000931536, ENST00000945285, ENST00001090666, ENST00001090667, ENST00001090668, ENST00001142805

RefSeq mRNA: 1 — MANE Select: NM_080677 NM_080677

CCDS: CCDS11601

Canonical transcript exons

ENST00000579991 — 3 exons

Exon	Start	End
ENSE00000820250	58087082	58087222
ENSE00001291217	58083419	58083683
ENSE00002718456	58089142	58095542

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.4538 / max 598.9114, expressed in 1825 samples.

Highest expression (Bgee): medial globus pallidus, sperm, ventricle myocardium, globus pallidus, cardiac muscle of right atrium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DYNLL2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 36 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	3.1e-22	+0.27	17:58093234:C:T
Skin Sun Exposed Lower leg	eqtl	1.8e-20	+0.25	17:58091010:G:A
Nerve Tibial	eqtl	4.1e-19	+0.23	17:58091010:G:A
Testis	eqtl	5.0e-17	+0.33	17:58091010:G:A
Esophagus Mucosa	eqtl	1.7e-15	-0.58	17:58090517:C:T
Muscle Skeletal	eqtl	2.4e-14	+0.17	17:58093234:C:T
Adipose Subcutaneous	eqtl	3.9e-14	+0.23	17:58093234:C:T
Colon Sigmoid	eqtl	5.0e-14	+0.25	17:58091010:G:A
Esophagus Muscularis	eqtl	4.6e-13	+0.19	17:58091010:G:A
Colon Transverse	eqtl	4.0e-10	+0.20	17:58094333:GTGA:G
Skin Not Sun Exposed Suprapubic	eqtl	6.9e-10	+0.19	17:58101539:T:C
Artery Tibial	eqtl	7.0e-10	+0.16	17:58091010:G:A
Cells Cultured fibroblasts	eqtl	2.1e-09	+0.15	17:58097128:G:A
Stomach	eqtl	1.4e-08	+0.25	17:58091010:G:A
Pancreas	eqtl	1.8e-08	+0.30	17:58091010:G:A
Brain Frontal Cortex BA9	eqtl	1.9e-08	+0.20	17:58094333:GTGA:G
Lung	eqtl	5.9e-08	+0.21	17:58091010:G:A
Cells EBV-transformed lymphocytes	eqtl	2.1e-07	+0.19	17:58082201:C:T
Breast Mammary Tissue	eqtl	9.3e-07	+0.18	17:58098842:A:T
Brain Caudate basal ganglia	eqtl	2.4e-06	-0.39	17:58074735:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
161893	68.4538	1825

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	99.19	gold quality
sperm	CL:0000019	98.98	gold quality
left ventricle myocardium	UBERON:0006566	98.98	gold quality
globus pallidus	UBERON:0001875	98.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.66	gold quality
oviduct epithelium	UBERON:0004804	98.56	gold quality
upper arm skin	UBERON:0004263	98.52	gold quality
ileal mucosa	UBERON:0000331	98.27	gold quality
pons	UBERON:0000988	98.18	gold quality
superior vestibular nucleus	UBERON:0007227	98.06	gold quality
substantia nigra pars compacta	UBERON:0001965	98.04	gold quality
ventral tegmental area	UBERON:0002691	97.95	gold quality
kidney epithelium	UBERON:0004819	97.94	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.93	gold quality
medulla oblongata	UBERON:0001896	97.81	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.78	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.66	gold quality
lateral globus pallidus	UBERON:0002476	97.62	gold quality
midbrain	UBERON:0001891	97.55	gold quality
tendon of biceps brachii	UBERON:0008188	97.53	gold quality
substantia nigra	UBERON:0002038	97.50	gold quality
parietal lobe	UBERON:0001872	97.44	gold quality
myocardium	UBERON:0002349	97.42	gold quality
postcentral gyrus	UBERON:0002581	97.42	gold quality
subthalamic nucleus	UBERON:0001906	97.38	gold quality
superior frontal gyrus	UBERON:0002661	97.34	gold quality
inferior vagus X ganglion	UBERON:0005363	97.29	gold quality
occipital lobe	UBERON:0002021	97.18	gold quality
putamen	UBERON:0001874	97.17	gold quality
primary visual cortex	UBERON:0002436	97.13	gold quality
endothelial cell	CL:0000115	97.00	gold quality
hypothalamus	UBERON:0001898	96.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.92	gold quality
tibialis anterior	UBERON:0001385	96.87	gold quality
nucleus accumbens	UBERON:0001882	96.86	gold quality
middle temporal gyrus	UBERON:0002771	96.79	gold quality
heart right ventricle	UBERON:0002080	96.78	gold quality
entorhinal cortex	UBERON:0002728	96.69	gold quality
caudate nucleus	UBERON:0001873	96.65	gold quality
temporal lobe	UBERON:0001871	96.58	gold quality
vastus lateralis	UBERON:0001379	96.55	gold quality
dorsal root ganglion	UBERON:0000044	96.52	gold quality
amygdala	UBERON:0001876	96.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.48	gold quality
quadriceps femoris	UBERON:0001377	96.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.35	gold quality
superficial temporal artery	UBERON:0001614	96.21	gold quality
cerebral cortex	UBERON:0000956	96.17	gold quality
spinal cord	UBERON:0002240	96.15	gold quality
anterior cingulate cortex	UBERON:0009835	96.14	gold quality
frontal cortex	UBERON:0001870	96.11	gold quality
pigmented layer of retina	UBERON:0001782	96.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.07	gold quality
neocortex	UBERON:0001950	96.04	gold quality
Ammon’s horn	UBERON:0001954	96.01	gold quality
brain	UBERON:0000955	96.00	gold quality
adult organism	UBERON:0007023	95.98	gold quality
prefrontal cortex	UBERON:0000451	95.97	gold quality
forebrain	UBERON:0001890	95.92	gold quality
nasal cavity epithelium	UBERON:0005384	95.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.84	gold quality
cerebellum	UBERON:0002037	95.75	gold quality
gingival epithelium	UBERON:0001949	95.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.65	gold quality
skeletal muscle tissue	UBERON:0001134	95.59	gold quality
right frontal lobe	UBERON:0002810	95.59	gold quality
cerebellar cortex	UBERON:0002129	95.58	gold quality
cerebellar hemisphere	UBERON:0002245	95.51	gold quality
cardiac ventricle	UBERON:0002082	95.42	gold quality
gingiva	UBERON:0001828	95.37	gold quality
heart left ventricle	UBERON:0002084	95.37	gold quality
biceps brachii	UBERON:0001507	95.36	gold quality
trigeminal ganglion	UBERON:0001675	95.34	gold quality
ganglionic eminence	UBERON:0004023	95.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.07	gold quality
muscle tissue	UBERON:0002385	94.97	gold quality
cerebellar vermis	UBERON:0004720	94.94	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.73	gold quality
caput epididymis	UBERON:0004358	94.69	gold quality
parotid gland	UBERON:0001831	94.65	gold quality
apex of heart	UBERON:0002098	94.57	gold quality
seminal vesicle	UBERON:0000998	94.51	gold quality
germinal epithelium of ovary	UBERON:0001304	94.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.34	gold quality
deltoid	UBERON:0001476	94.31	gold quality
islet of Langerhans	UBERON:0000006	94.10	gold quality
corpus epididymis	UBERON:0004359	94.05	gold quality
gastrocnemius	UBERON:0001388	93.94	gold quality
muscle of leg	UBERON:0001383	93.86	gold quality
buccal mucosa cell	CL:0002336	93.83	gold quality
renal medulla	UBERON:0000362	93.74	gold quality
placenta	UBERON:0001987	93.68	gold quality
heart	UBERON:0000948	93.67	gold quality
body of tongue	UBERON:0011876	93.57	gold quality
saphenous vein	UBERON:0007318	93.29	gold quality
nasal cavity mucosa	UBERON:0001826	93.13	gold quality
epithelium of mammary gland	UBERON:0003244	93.00	gold quality
cauda epididymis	UBERON:0004360	93.00	gold quality
mammary duct	UBERON:0001765	92.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.18

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Caudate putamen	tissue	537.3
Frontal cortex	tissue	494.6
Pons	tissue	333.2
Thalamus	tissue	295.7
Spinal cord	tissue	293.4
Superior colliculi	tissue	293.3
Midbrain	tissue	290.3
Substantia nigra	tissue	277.6
Medulla oblongata	tissue	274.6
Putamen	tissue	262.3
Hypothalamus	tissue	252.9
Cerebellum	tissue	242.3
Periaqueductal gray	tissue	232.8
Cerebral cortex	tissue	225.2
Occipital cortex	tissue	225.2
Somatosensory cortex	tissue	224.8
Ventral forebrain	tissue	223.6
Septum	tissue	218.9
Motor cortex	tissue	211.3
Prefrontal cortex	tissue	208.0
Basal ganglia	tissue	202.6
Hippocampal formation	tissue	188.6
Entorhinal cortex	tissue	188.6
Temporal cortex	tissue	186.1
Retrosplenial and cingulate cortex	tissue	178.8
Retrosplenial cortex	tissue	175.7
Corpus callosum	tissue	168.2
Insular cortex	tissue	167.1
Amygdala	tissue	161.1
Olfactory bulb	tissue	130.1
Locus coeruleus	tissue	118.6
Skeletal muscle	tissue	106.5
Postcentral gyrus	tissue	86.5
Nucleus accumbens	tissue	85.7
Hippocampus	tissue	68.7
Tongue	tissue	54.9
Heart muscle	tissue	47.1
Parathyroid gland	tissue	44.4
Adrenal gland	tissue	39.5
Choroid plexus	tissue	39.4
Kidney	tissue	39.4
Retina	tissue	38.2
Liver	tissue	32.9
Thyroid gland	tissue	30.9
Salivary gland	tissue	29.1
Placenta	tissue	28.5
Prostate	tissue	28.5
Pituitary gland	tissue	26.9
Seminal vesicle	tissue	24.8
Duodenum	tissue	23.5
Adipose tissue	tissue	23.0
Small intestine	tissue	22.9
Epididymis	tissue	21.2
Thymus	tissue	21.0
Colon	tissue	20.8
Rectum	tissue	18.8
Stomach 1	tissue	18.5
Testis	tissue	18.4
Fallopian tube	tissue	18.3
Skin 1	tissue	18.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Ventral spinal cord (293.4), Dorsal spinal cord (230.3), Subiculum (178.4), Dorsal hippocampus (175.0), Ventral hippocampus (169.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DYNLL2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 95 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-623	99.76	68.16	1170

Functional genomics

gnomAD constraint: pLI 0.96, LOEUF 0.462, missense Z 2.81 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000579991 — one region, missense o/e 0.32.

Literature-anchored findings (GeneRIF, showing 2)

• the thermodynamic and kinetic fine-tuning of binding of various ligands to DYNLL could have physiological relevance in its interaction network. (PMID:20889982)
• The DYNLL2 binding region, located in an intrinsically disordered domain of the myo5a tail, has a nascent helical character. (PMID:25312846)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dynll2b	ENSDARG00000005172
danio_rerio	dynll2a	ENSDARG00000069790
mus_musculus	Dynll2	ENSMUSG00000020483
rattus_norvegicus	Dynll2	ENSRNOG00000008921
drosophila_melanogaster	ctp	FBGN0011760
drosophila_melanogaster	Cdlc2	FBGN0026141
caenorhabditis_elegans		WBGENE00001005

Paralogs (1): DYNLL1 (ENSG00000088986)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915347) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased anxiety-related response	1
decreased locomotor activity	1
decreased startle reflex	1
abnormal vocalization	1
impaired glucose tolerance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	A4F4L4	100.0%	Diamond
Macaca fascicularis	P61273	100.0%	Diamond
Bos taurus	P61285	100.0%	Diamond
Oryctolagus cuniculus	P63169	100.0%	Diamond
Chlamydomonas reinhardtii	Q39580	95.3%	Diamond
Heliocidaris crassispina	O02414	94.4%	Diamond
Schizosaccharomyces pombe 972h-	Q9UR05	78.6%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CWX4	78.4%	Diamond
Eremothecium gossypii ATCC 10895	Q759T0	78.4%	Diamond
Schistosoma mansoni	Q94748	76.4%	Diamond
Aspergillus nidulans FGSC A4	O94111	75.3%	Diamond
Saccharomyces cerevisiae S288C	Q02647	72.3%	Diamond
Dictyostelium discoideum	Q86A88	67.1%	Diamond
Debaryomyces hansenii CBS767	Q6BZF8	65.1%	Diamond
Nakaseomyces glabratus CBS 138	Q6FUJ0	64.6%	Diamond
Tetrahymena thermophila SB210	A4VE64	57.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
OR4D1	protein-coding	26689
SRSF1	protein-coding	6426
DYNLL2-DT	ncRNA	101927666
VEZF1	protein-coding	7716
OR4D2	protein-coding	124538
MKS1	protein-coding	54903
EPX	protein-coding	8288

Protein

Protein identifiers

Dynein light chain 2, cytoplasmic — Q96FJ2 (reviewed: Q96FJ2)

Alternative names: 8 kDa dynein light chain b, Dynein light chain LC8-type 2

All UniProt accessions (1): Q96FJ2

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. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.

Subunit / interactions. Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits which present 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. Dynein ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1I1. Interacts with BMF. Component of the myosin V motor complex. Interacts with BCAS1. Interacts with Basson/BSN. Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton. Interacts with IQUB.

Subcellular location. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the dynein light chain family.

RefSeq proteins (1): NP_542408* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001372	Dynein_light_chain_typ-1/2	Family
IPR019763	Dynein_light_1/2_CS	Conserved_site
IPR037177	DLC_sf	Homologous_superfamily

Pfam: PF01221

UniProt features (9 total): strand 4, helix 2, chain 1, site 1, turn 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
2XQQ	Human dynein light chain (DYNLL2) in complex with an in vitro evolved peptide …	X-RAY DIFFRACTION	1.31
4D07	DYNLL2 dynein light chain binds to an extended, unstructured linear motif of myosin 5a …	X-RAY DIFFRACTION	1.85
7CNU	Crystal structure of DLC2 in complex with BMF peptide	X-RAY DIFFRACTION	2
3P8M	Human dynein light chain (DYNLL2) in complex with an in vitro evolved peptide dimerized …	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FJ2-F1	95.73	0.94

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; mid piece; nucleoplasm; principal piece

Antibody reliability (HPA): IF uncertain

Functional residue map

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

Catalytic / active sites (1)

Position	Role
41	interaction with myosin v motor complex

Function

Pathways and Gene Ontology

Reactome pathways

15 curated (TAS) of 53; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

53 pathways:

ID	Pathway	Evidence
R-HSA-9609690	HCMV Early Events ⚕	curated
R-HSA-139910	Activation of BMF and translocation to mitochondria	curated
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	curated
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic	curated
R-HSA-6807878	COPI-mediated anterograde transport	curated
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	curated
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	curated
R-HSA-5620924	Intraflagellar transport	curated
R-HSA-2132295	MHC class II antigen presentation	curated
R-HSA-1632852	Macroautophagy	curated
R-HSA-68877	Mitotic Prometaphase	curated
R-HSA-9979719	Processing of antigen in germinal center B cells	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-2500257	Resolution of Sister Chromatid Cohesion	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-9609646	HCMV Infection ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-114452	Activation of BH3-only proteins	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-9646399	Aggrephagy	electronic
R-HSA-141424	Amplification of signal from the kinetochores	—
R-HSA-109581	Apoptosis	—
R-HSA-446203	Asparagine N-linked glycosylation	—
R-HSA-9612973	Autophagy	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-5617833	Cilium Assembly	—
R-HSA-199977	ER to Golgi Anterograde Transport	—
R-HSA-8856688	Golgi-to-ER retrograde transport	—
R-HSA-168256	Immune System	—
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic	—
R-HSA-109606	Intrinsic Pathway for Apoptosis	—
R-HSA-68886	M Phase	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-69618	Mitotic Spindle Checkpoint	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-9663891	Selective autophagy	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-948021	Transport to the Golgi and subsequent modification	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 283 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CHROMOSOME_SEPARATION, REACTOME_MEMBRANE_TRAFFICKING, GOCC_MICROTUBULE_ORGANIZING_CENTER, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (6): cilium movement (GO:0003341), flagellated sperm motility (GO:0030317), positive regulation of intracellular transport (GO:0032388), intraciliary retrograde transport (GO:0035721), positive regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090267), microtubule-based process (GO:0007017)

GO Molecular Function (5): identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), dynein intermediate chain binding (GO:0045505), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (22): male germ cell nucleus (GO:0001673), nucleus (GO:0005634), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856), cytoplasmic dynein complex (GO:0005868), microtubule (GO:0005874), plasma membrane (GO:0005886), cilium (GO:0005929), axoneme (GO:0005930), postsynaptic density (GO:0014069), membrane (GO:0016020), myosin V complex (GO:0031475), sperm flagellum (GO:0036126), ciliary tip (GO:0097542), 9+2 motile cilium (GO:0097729), 9+0 non-motile cilium (GO:0097731), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), microtubule associated complex (GO:0005875), microtubule cytoskeleton (GO:0015630), dynein complex (GO:0030286)

Reactome top-level categories

19 top-level categories:

Category	Pathways
Mitotic Prometaphase	2
Activation of BH3-only proteins	1
Amplification of signal from the kinetochores	1
Autophagy	1
Adaptive Immune System	1
Mitotic Anaphase	1
Cellular responses to stress	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
Affinity selection of immunoglobulins	1
Programmed Cell Death	1
Apoptosis	1
Intrinsic Pathway for Apoptosis	1
Immune System	1

GO top-level categories

48 GO namespaces:

Category	Terms
cellular anatomical structure	5
protein binding	3
binding	2
microtubule cytoskeleton	2
synapse	2
microtubule-based movement	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
regulation of intracellular transport	1
intracellular transport	1
positive regulation of cellular process	1
positive regulation of transport	1
intraciliary transport	1
mitotic spindle assembly checkpoint signaling	1
positive regulation of cell cycle process	1
positive regulation of spindle checkpoint	1
regulation of mitotic cell cycle spindle assembly checkpoint	1
cellular process	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intracellular membraneless organelle	1
dynein complex	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
asymmetric synapse	1
postsynaptic specialization	1
unconventional myosin complex	1
9+2 motile cilium	1
cilium	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
non-motile cilium	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 33 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
9+0 non-motile cilium	CC	direct assay
centrosome	CC	direct assay
cytoskeleton	CC	direct assay
glutamatergic synapse	CC	direct assay
membrane	CC	high-throughput assay
nucleus	CC	high-throughput assay
postsynapse	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,556 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNLL2	DYNLT3	P51808	741
DYNLL2	DYNLRB1	Q9NP97	720
DYNLL2	GPHN	Q9NQX3	713
DYNLL2	DYNLT1	P63172	687
DYNLL2	DYNLRB2	Q8TF09	685
DYNLL2	DYNC1LI2	O43237	677
DYNLL2	DYNC1LI1	Q9Y6G9	667
DYNLL2	DYNC1H1	Q14204	667
DYNLL2	DYNC1I1	O14576	637
DYNLL2	DYNC2I2	Q96EX3	609
DYNLL2	DYNLT2B	Q8WW35	605
DYNLL2	SYP	P08247	599
DYNLL2	DYNC2LI1	Q8TCX1	597
DYNLL2	DYNC2I1	Q8WVS4	589
DYNLL2	DYNC1I2	Q13409	508

IntAct

Human interaction partners of DYNLL2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 60 partners by confidence:

Partner	Interaction type	MIscore	Records
FAM117B	physical association	0.880	7
XIAP	physical association	0.850	3
TLK1	physical association	0.840	3
DNAL4	physical association	0.800	6
HMBOX1	physical association	0.800	4
HOMER3	physical association	0.800	4
KANK2	physical association	0.800	3
SECISBP2L	physical association	0.740	3
MORN3	physical association	0.670	4
REDIC1	physical association	0.670	4
DYNC1I1	physical association	0.660	1
BLTP3B	association	0.640	3
BMF	physical association	0.560	3
C14orf119	physical association	0.560	3
DPPA3	physical association	0.560	3
GABARAPL2	physical association	0.560	3
IHO1	physical association	0.560	3
MEOX2	physical association	0.560	3
OTUD6A	physical association	0.560	3
PKIA	physical association	0.560	3
PKIG	physical association	0.560	3
RASGRP3	physical association	0.560	3
SEPTIN4	physical association	0.560	3
SMCP	physical association	0.560	3
SPAG8	physical association	0.560	3
ZAR1	physical association	0.560	3
GPRIN2	physical association	0.550	2
THAP10	physical association	0.550	2
SHMT2	association	0.510	2
SUDS3	physical association	0.400	1

BioGRID (444 interactions; top human partners by supporting records): DYNLL1 (Co-fractionation; 11 records), DLGAP1 (Two-hybrid; 6 records), MYO5A (Two-hybrid; 6 records), AMOT (Affinity Capture-MS; 5 records), DYRK1A (Affinity Capture-MS; 5 records), BMF (Two-hybrid; 4 records), DNAL4 (Two-hybrid; 4 records), DYNC1I2 (Affinity Capture-MS; 4 records), FAM117B (Affinity Capture-MS; 4 records), NEK9 (Affinity Capture-MS; 4 records), TLK1 (Two-hybrid; 4 records), TLK2 (Affinity Capture-MS; 4 records), XIAP (Two-hybrid; 4 records), AMBRA1 (Affinity Capture-MS; 3 records), BCL2L11 (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
DYNLL2	down-regulates	AMBRA1	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
Dynein-2 complex, cytoplasmic	12	DYNC2H1, DYNC2I1, DYNC2I2, DYNLL1, DYNLL2, DYNLRB1, DYNLT3, NUDCD3, DYNC2LI1, DYNLRB2, DYNLT1, DYNLT2B
DLGAP1-DLG4-DYNLL2 complex	3	DLG4, DLGAP1, DYNLL2
Dynein light chain complex (DYNLL1, DYNLL2)	2	DYNLL1, DYNLL2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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
Regulation of PLK1 Activity at G2/M Transition	6	22.4×	6e-05
Anchoring of the basal body to the plasma membrane	5	16.6×	9e-04
Mitotic Prometaphase	5	10.2×	4e-03

Disease & clinical

Genetic variants

Variant evidence for DYNLL2: 7 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 234):

Position(s)	Effect	Δscore	Sites
17:58087080–58087081	acceptor_loss	1.0000	6
17:58087220	donor_gain	1.0000
17:58083684–58083685	donor_loss	0.9900	5
17:58087077	acceptor_gain	0.9900
17:58087223–58087224	donor_loss	0.9900	5
17:58089140–58089141	acceptor_loss	0.9900	6
17:58083607	donor_gain	0.9800
17:58087233	donor_gain	0.9700
17:58084308	donor_gain	0.9600
17:58089201	donor_gain	0.9500

AlphaMissense

423 missense substitutions predicted likely pathogenic (of 601 scored), across 85 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M13	9	0.912	0.998
H55	8	0.994	0.999
H68	8	0.994	1.000
D12	8	0.989	0.998
D47	8	0.987	0.999
F73	8	0.972	0.999
F62	8	0.964	1.000
S64	8	0.963	0.997
D37	8	0.955	0.993
F86	8	0.950	1.000
F76	8	0.930	0.993
F46	8	0.928	0.994
W54	7	0.999	1.000
E35	7	0.983	0.997
C56	7	0.972	1.000
K43	7	0.968	1.000
E69	7	0.965	0.995
N10	7	0.884	0.991
N61	7	0.876	0.991
Q18	7	0.847	0.993

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.92e-10
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	1.44e-06
Kidney Renal Clear Cell Carcinoma (validation)	favorable	2.72e-06
Pancreatic Adenocarcinoma (TCGA)	favorable	0.000953

Disease associations

OMIM: gene MIM:608942 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_1201	Blood protein levels	3e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067226 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

7 measured of 7 human assays (8 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
7-bromo-2-[1-(4-chlorophenyl)cyclopropyl]-9-oxo-2,3,3a,4,4a,5,6,7,8,8a-decahydro-1H-pyrazolo[5,1-b]quinazoline-3-carbonitrile	IC50	290 nM	US-11192893: Pyrazoloquinazolinone antitumor agents
2-[4-(4-chlorophenyl)cyclohexyl]-9-oxo-2,3,3a,4,4a,5,6,7,8,8a-decahydro-1H-pyrazolo[5,1-b]quinazoline-3-carbonitrile	IC50	620 nM	US-11192893: Pyrazoloquinazolinone antitumor agents
2-[1-(4-chlorophenyl)cyclopropyl]-9-oxo-2,3,3a,4,4a,5,6,7,8,8a-decahydro-1H-pyrazolo[5,1-b]quinazoline-3-carbonitrile	IC50	710 nM	US-11192893: Pyrazoloquinazolinone antitumor agents
2-[3-(4-chlorophenoxy)propyl]-9-oxo-2,3,3a,4,4a,5,6,7,8,8a-decahydro-1H-pyrazolo[5,1-b]quinazoline-3-carbonitrile	IC50	730 nM	US-11192893: Pyrazoloquinazolinone antitumor agents
CHEMBL5653589	KD	1440 nM
2-[1-(4-chlorophenyl)cyclopropyl]-7-iodo-5-oxo-2,3,3a,4,5a,6,7,8,9,9a-decahydro-1H-pyrazolo[1,5-a]quinazoline-3-carbonitrile	IC50	2600 nM	US-11192893: Pyrazoloquinazolinone antitumor agents
2-[1-(4-chlorophenyl)cyclopropyl]-5-oxo-7-(trifluoromethyl)-2,3,3a,4,5a,6,7,8,9,9a-decahydro-1H-pyrazolo[1,5-a]quinazoline-3-carbonitrile	IC50	3300 nM	US-11192893: Pyrazoloquinazolinone antitumor agents

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.09	Kd	80.89	nM	CHEMBL3752910
6.83	ED50	148	nM	CHEMBL3752910
6.60	Kd	250.5	nM	CHEMBL5653589
6.34	ED50	458.5	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148275: Binding affinity to human DYNLL2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0809	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148275: Binding affinity to human DYNLL2 incubated for 45 mins by Kinobead based pull down assay	kd	0.2505	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases expression	3
bisphenol A	increases expression	2
Leflunomide	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
resorcinol	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases expression	1
Copper	affects binding, decreases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Disulfiram	affects binding, decreases expression	1
Colforsin	increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Phenobarbital	affects expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651317	Binding	Binding affinity to human DYNLL2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DYNLL2 across ~30M SureChEMBL compounds — explore on Sugi Predict.