DYNLRB2

Summary

DYNLRB2 (dynein light chain roadblock-type 2, HGNC:15467) is a protein-coding gene on chromosome 16q23.2, encoding Dynein light chain roadblock-type 2 (Q8TF09). 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 microtubule-based movement. Predicted to be located in ciliary tip. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in centrosome and cytoplasm. Biomarker of hepatocellular carcinoma.

Source: NCBI Gene 83657 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 34 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_130897

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15467
Approved symbol	DYNLRB2
Name	dynein light chain roadblock-type 2
Location	16q23.2
Locus type	gene with protein product
Status	Approved
Aliases	DNLC2B, ROBLD2
Ensembl gene	ENSG00000168589
Ensembl biotype	protein_coding
OMIM	607168
Entrez	83657

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 nonsense_mediated_decay

ENST00000305904, ENST00000338542, ENST00000561880, ENST00000562982, ENST00000568035, ENST00000570222

RefSeq mRNA: 2 — MANE Select: NM_130897 NM_001305017, NM_130897

CCDS: CCDS10929, CCDS76904

Canonical transcript exons

ENST00000305904 — 4 exons

Exon	Start	End
ENSE00001378357	80543276	80543351
ENSE00002598485	80540993	80541079
ENSE00003492095	80550515	80550811
ENSE00003626380	80549484	80549651

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 99.60.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2686 / max 288.6944, expressed in 402 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155131	1.1749	374
155132	0.0937	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.60	gold quality
right uterine tube	UBERON:0001302	99.17	gold quality
bronchus	UBERON:0002185	99.03	gold quality
left testis	UBERON:0004533	98.82	gold quality
right testis	UBERON:0004534	98.59	gold quality
sperm	CL:0000019	98.20	gold quality
adult organism	UBERON:0007023	97.42	gold quality
testis	UBERON:0000473	96.76	gold quality
oviduct epithelium	UBERON:0004804	94.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.42	gold quality
caput epididymis	UBERON:0004358	92.82	gold quality
fallopian tube	UBERON:0003889	89.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.99	gold quality
epithelium of nasopharynx	UBERON:0001951	84.58	gold quality
corpus epididymis	UBERON:0004359	83.81	gold quality
nasal cavity epithelium	UBERON:0005384	82.30	gold quality
trachea	UBERON:0003126	81.90	gold quality
hypothalamus	UBERON:0001898	81.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.25	gold quality
caudate nucleus	UBERON:0001873	80.12	gold quality
right lung	UBERON:0002167	79.78	gold quality
nucleus accumbens	UBERON:0001882	78.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.47	gold quality
nasal cavity mucosa	UBERON:0001826	78.37	gold quality
amygdala	UBERON:0001876	77.79	gold quality
adenohypophysis	UBERON:0002196	76.72	gold quality
spinal cord	UBERON:0002240	76.67	gold quality
anterior cingulate cortex	UBERON:0009835	76.18	gold quality
putamen	UBERON:0001874	75.92	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	63.70
E-HCAD-1	yes	30.67
E-GEOD-134144	yes	30.06
E-MTAB-10287	yes	26.12
E-GEOD-130148	yes	12.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting DYNLRB2, 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-223-3P	99.99	70.14	1140
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-34C-3P	98.11	65.60	858
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-3189-3P	96.80	66.34	896

Literature-anchored findings (GeneRIF, showing 2)

• Among the total 68 liver cancer samples tested, DNLC2B was down-regulated in 28 cases. (PMID:11750132)
• Findings indicate that km23-2 (DYNLRB2) is required for Smad3-dependent TGFbeta signaling. Km23-2 has functions in TGFbeta signaling that are distinct from those for km23-1 (DYNLRB1). (PMID:19711352)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dynlrb2	ENSDARG00000089952
mus_musculus	Dynlrb2	ENSMUSG00000034467
rattus_norvegicus	Dynlrb2	ENSRNOG00000012450
drosophila_melanogaster	robl	FBGN0024196
caenorhabditis_elegans		WBGENE00012004

Paralogs (1): DYNLRB1 (ENSG00000125971)

Protein

Protein identifiers

Dynein light chain roadblock-type 2 — Q8TF09 (reviewed: Q8TF09)

Alternative names: Dynein light chain 2B, cytoplasmic, Roadblock domain-containing protein 2

All UniProt accessions (6): Q8TF09, A0A140VJH9, H3BNG9, H3BPA0, H3BQI1, Q7Z4M1

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.

Subunit / interactions. Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by 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. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1I1 and DYNC1I2. Self-associates. Interacts with DYNLRB1.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. High expression in heart, brain, placenta, skeletal muscle, prostate and small intestine; moderate in kidney, pancreas, spleen, testis, ovary and colon; low in lung, liver, thymus and leukocyte.

Miscellaneous. Expression is significantly down-regulated in hepatocellular carcinoma (HCC) patients.

Similarity. Belongs to the GAMAD family.

RefSeq proteins (2): NP_001291946, NP_570967* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004942	Roadblock/LAMTOR2_dom	Domain
IPR016561	DYNLRB1/2	Family

Pfam: PF03259

UniProt features (4 total): initiator methionine 1, chain 1, modified residue 1, sequence 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-Q8TF09-F1	95.08	0.91

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 143 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CHROMOSOME_SEPARATION, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_ORGANELLE_FISSION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_CILIUM_ORGANIZATION

GO Biological Process (1): microtubule-based movement (GO:0007018)

GO Molecular Function (2): microtubule motor activity (GO:0003777), dynein intermediate chain binding (GO:0045505)

GO Cellular Component (8): cytoplasm (GO:0005737), centrosome (GO:0005813), cytoplasmic dynein complex (GO:0005868), microtubule (GO:0005874), cilium (GO:0005929), ciliary tip (GO:0097542), cytoskeleton (GO:0005856), dynein complex (GO:0030286)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
microtubule-based process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
protein binding	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
intracellular membraneless organelle	1
microtubule associated complex	1
catalytic complex	1

Protein interactions and networks

STRING

1416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNLRB2	DYNLL2	Q96FJ2	794
DYNLRB2	DYNLT3	P51808	786
DYNLRB2	DYNLT1	P63172	731
DYNLRB2	DYNLL1	P63167	722
DYNLRB2	DYNLT2B	Q8WW35	703
DYNLRB2	DYNC1LI2	O43237	615
DYNLRB2	DYNC2LI1	Q8TCX1	608
DYNLRB2	DYNC1I1	O14576	601
DYNLRB2	DYNC1LI1	Q9Y6G9	591
DYNLRB2	DYNC2I2	Q96EX3	570
DYNLRB2	DYNC2I1	Q8WVS4	570
DYNLRB2	DYNC1I2	Q13409	518
DYNLRB2	DYNLT4	Q5JR98	510
DYNLRB2	GPR119	Q8TDV5	500
DYNLRB2	DYNLT5	Q8N7M0	485

IntAct

13 interactions, top by confidence:

A	B	Type	Score
DYNLRB2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.510
DYNLRB2	MYH9	psi-mi:“MI:0915”(physical association)	0.400
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC26A10P	DDX10	psi-mi:“MI:0914”(association)	0.350
DYNLRB2	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.000
PAFAH1B1	DYNLRB2	psi-mi:“MI:0915”(physical association)	0.000
DYNLT1	DYNLRB2	psi-mi:“MI:0915”(physical association)	0.000
KIF7	DYNLRB2	psi-mi:“MI:0915”(physical association)	0.000
DYNC2I1	DYNLRB2	psi-mi:“MI:0915”(physical association)	0.000
DYNLRB2	DYNLT2B	psi-mi:“MI:0915”(physical association)	0.000
DYNLRB2	DYNC2I2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): DYNLRB2 (Co-fractionation), GTF2H2C (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), TCTEX1D2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Proximity Label-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), DYNLRB2 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A7RT29, A7S6M8, A9UMU8, B0G185, D3ZVF4, E2QV03, F1SRI0, O02173, O43041, O94697, P0DI81, P0DI82, P22214, P35181, P49231, P53290, P62627, P62628, Q00582, Q08CN0, Q0P3X8, Q21193, Q28IG8, Q32P85, Q3T0F2, Q3T140, Q4PM15, Q54BN3, Q54CU7, Q54QW5, Q54RV6, Q54UB5, Q54UU1, Q557G3, Q5RES6, Q5ZKP4, Q6C880, Q6CJA0, Q74ZD2, Q7TN05

Diamond homologs: P62627, P62628, Q32P85, Q3T140, Q8TF09, Q9DAJ5, Q9NP97

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	28
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3243515	NC_000016.9:g.(?78420737)(81991603_?)del	Pathogenic
564356	GRCh37/hg19 16q23.2-24.3(chr16:79400436-90155062)x3	Pathogenic
655227	NC_000016.10:g.(?78278583)(80589366_?)del	Pathogenic
979478	GRCh37/hg19 16q23.2-23.3(chr16:80483625-82044152)x1	Likely pathogenic

SpliceAI

678 predictions. Top by Δscore:

Variant	Effect	Δscore
16:80541135:G:GT	donor_gain	0.9900
16:80549478:TAATA:T	acceptor_loss	0.9900
16:80549480:ATAG:A	acceptor_loss	0.9900
16:80549481:TAGG:T	acceptor_loss	0.9900
16:80549482:A:T	acceptor_loss	0.9900
16:80549483:G:GC	acceptor_loss	0.9900
16:80541233:G:GT	donor_gain	0.9800
16:80541273:G:GT	donor_gain	0.9800
16:80543270:TTTCA:T	acceptor_loss	0.9800
16:80543271:TTCA:T	acceptor_loss	0.9800
16:80543272:TCA:T	acceptor_loss	0.9800
16:80543273:CAG:C	acceptor_loss	0.9800
16:80543274:A:T	acceptor_loss	0.9800
16:80543275:GGCA:G	acceptor_gain	0.9800
16:80549013:G:T	donor_gain	0.9800
16:80549483:GGT:G	acceptor_gain	0.9800
16:80541211:G:GT	donor_gain	0.9700
16:80541371:G:T	donor_gain	0.9700
16:80543267:CTCTT:C	acceptor_loss	0.9700
16:80543268:TCTTT:T	acceptor_loss	0.9700
16:80543269:CTTTC:C	acceptor_loss	0.9700
16:80541225:G:T	donor_gain	0.9600
16:80541396:A:T	donor_gain	0.9600
16:80549482:A:AG	acceptor_gain	0.9600
16:80549483:G:GG	acceptor_gain	0.9600
16:80550514:GATAA:G	acceptor_gain	0.9600
16:80541227:C:T	donor_gain	0.9500
16:80541251:C:T	donor_gain	0.9500
16:80541369:GGGGA:G	donor_gain	0.9500
16:80541370:GGGAG:G	donor_gain	0.9500

AlphaMissense

630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:80549561:G:C	A53P	0.996
16:80549574:T:A	V57D	0.996
16:80549562:C:A	A53D	0.995
16:80549577:G:C	R58P	0.993
16:80549610:T:C	L69P	0.992
16:80549550:T:C	L49P	0.991
16:80543337:T:A	V22D	0.990
16:80549614:G:C	R70S	0.989
16:80549614:G:T	R70S	0.989
16:80543322:T:A	V17D	0.988
16:80549496:G:C	R31P	0.986
16:80549621:T:C	S73P	0.986
16:80549613:G:T	R70M	0.985
16:80543328:G:A	G19E	0.984
16:80549643:T:A	V80E	0.984
16:80549646:C:A	A81D	0.984
16:80543351:G:C	G27R	0.982
16:80549616:T:A	I71N	0.982
16:80543304:T:G	I11S	0.981
16:80549613:G:C	R70T	0.981
16:80543304:T:A	I11N	0.979
16:80550530:T:C	L88P	0.979
16:80550536:T:A	V90D	0.979
16:80549601:T:G	L66R	0.977
16:80549606:T:C	F68L	0.977
16:80549608:T:A	F68L	0.977
16:80549608:T:G	F68L	0.977
16:80549645:G:C	A81P	0.977
16:80550542:A:C	Q92P	0.977
16:80543304:T:C	I11T	0.976

dbSNP variants (sampled 300 via entrez): RS1000109417 (16:80542529 A>G), RS1000313694 (16:80547159 C>G), RS1000508127 (16:80539152 C>T), RS1000703531 (16:80549982 T>C), RS1001016132 (16:80543147 T>C), RS1001774301 (16:80540062 A>G,T), RS1001927609 (16:80540033 A>T), RS1001939907 (16:80544518 C>G), RS1001984337 (16:80549414 A>G,T), RS1002046752 (16:80549387 C>G), RS1002119192 (16:80544734 G>A), RS1002335036 (16:80549165 A>C), RS1002483437 (16:80540946 G>A,C), RS1002877546 (16:80550187 C>G), RS1003094432 (16:80545522 G>T)

Disease associations

OMIM: gene MIM:607168 | disease phenotypes: MIM:308350, MIM:614322, MIM:601088, MIM:610202

GenCC curated gene-disease

Mondo (4): developmental and epileptic encephalopathy, 1 (MONDO:0010632), autosomal recessive spinocerebellar ataxia 12 (MONDO:0013687), Ayme-Gripp syndrome (MONDO:0010992), cataract 21 multiple types (MONDO:0012437)

Orphanet (3): Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency (Orphanet:284282), Early onset non-syndromic cataract (Orphanet:91492), OBSOLETE: AymÚ-Gripp syndrome (Orphanet:477668)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001277_17	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-09
GCST001872_10	Presence of antiphospholipid antibodies	1.000000e-06
GCST006291_50	Spherical equivalent or myopia (age of diagnosis)	2.000000e-11
GCST009869_63	Colorectal cancer	2.000000e-10
GCST010002_116	Refractive error	2.000000e-28
GCST90011898_47	Alanine aminotransferase levels	7.000000e-22
GCST90011899_44	Aspartate aminotransferase levels	2.000000e-15
GCST90011900_129	Serum alkaline phosphatase levels	8.000000e-80
GCST90013407_25	Liver enzyme levels (gamma-glutamyl transferase)	5.000000e-126
GCST90013663_53	Alanine aminotransferase levels	4.000000e-26
GCST90013664_65	Aspartate aminotransferase levels	9.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004847	age at onset
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C565703	Cataract, Pulverulent, Juvenile-Onset (supp.)
C563390	Cataracts, Congenital, with Sensorineural Deafness, Down Syndrome-Like Facial Appearance, Short Stature, and Mental Retardation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
Nickel	decreases expression	2
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
Temozolomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford