LIN52

Summary

LIN52 (lin-52 DREAM MuvB core complex component, HGNC:19856) is a protein-coding gene on chromosome 14q24.3, encoding Protein lin-52 homolog (Q52LA3). It is a selective cancer dependency (DepMap: 52.0% of cell lines).

Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleoplasm. Predicted to be part of DRM complex.

Source: NCBI Gene 91750 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 17 total
• Cancer dependency (DepMap): dependent in 52.0% of screened cell lines
• MANE Select transcript: NM_001024674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19856
Approved symbol	LIN52
Name	lin-52 DREAM MuvB core complex component
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205659
Ensembl biotype	protein_coding
OMIM	621288
Entrez	91750

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000553404, ENST00000554076, ENST00000554289, ENST00000554938, ENST00000555028, ENST00000899705, ENST00000899706, ENST00000899707, ENST00000899708, ENST00000899709, ENST00000962091, ENST00000962092, ENST00000962093

RefSeq mRNA: 3 — MANE Select: NM_001024674 NM_001024674, NM_001372005, NM_001372006

CCDS: CCDS32120

Canonical transcript exons

ENST00000555028 — 6 exons

Exon	Start	End
ENSE00002496537	74198922	74201493
ENSE00002513201	74084956	74084993
ENSE00003533748	74101155	74101238
ENSE00003553761	74097794	74097860
ENSE00003586238	74091232	74091306
ENSE00003689004	74095948	74095985

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9485 / max 110.7990, expressed in 1731 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140570	8.9485	1731

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.30	gold quality
kidney epithelium	UBERON:0004819	92.47	gold quality
oocyte	CL:0000023	91.96	gold quality
tibialis anterior	UBERON:0001385	90.59	gold quality
pancreatic ductal cell	CL:0002079	90.38	silver quality
left ventricle myocardium	UBERON:0006566	89.92	silver quality
cardiac muscle of right atrium	UBERON:0003379	89.01	silver quality
deltoid	UBERON:0001476	87.64	gold quality
ventricular zone	UBERON:0003053	87.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.40	gold quality
ileal mucosa	UBERON:0000331	86.57	gold quality
ganglionic eminence	UBERON:0004023	86.50	gold quality
endothelial cell	CL:0000115	86.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.53	gold quality
palpebral conjunctiva	UBERON:0001812	84.32	gold quality
middle temporal gyrus	UBERON:0002771	84.02	gold quality
cortical plate	UBERON:0005343	83.85	gold quality
pigmented layer of retina	UBERON:0001782	83.49	gold quality
primary visual cortex	UBERON:0002436	83.23	gold quality
bone marrow cell	CL:0002092	83.22	gold quality
vastus lateralis	UBERON:0001379	83.05	silver quality
quadriceps femoris	UBERON:0001377	83.04	silver quality
islet of Langerhans	UBERON:0000006	82.97	gold quality
substantia nigra pars compacta	UBERON:0001965	82.89	gold quality
tibia	UBERON:0000979	82.82	gold quality
jejunal mucosa	UBERON:0000399	82.77	gold quality
sperm	CL:0000019	82.75	gold quality
occipital lobe	UBERON:0002021	82.51	gold quality
cerebellar cortex	UBERON:0002129	82.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting LIN52, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4283	100.00	66.42	2097
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-6867-5P	100.00	82.21	3464
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4524A-3P	99.72	66.85	2406

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 52.0% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lin52	ENSDARG00000070833
mus_musculus	Lin52	ENSMUSG00000085793
rattus_norvegicus	Lin52	ENSRNOG00000043441
drosophila_melanogaster	lin-52	FBGN0029800
caenorhabditis_elegans		WBGENE00003035

Protein

Protein identifiers

Protein lin-52 homolog — Q52LA3 (reviewed: Q52LA3)

All UniProt accessions (2): B3KN83, G3V5T8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2.

Similarity. Belongs to the lin-52 family.

RefSeq proteins (3): NP_001019845, NP_001358934, NP_001358935 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018737	DREAM_LIN52	Family

Pfam: PF10044

UniProt features (7 total): helix 3, modified residue 2, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6C48	X-RAY DIFFRACTION	2.32
4YOO	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q52LA3-F1	77.10	0.28

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 (2): 24, 49

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133	G0 and Early G1
R-HSA-156711	Polo-like kinase mediated events
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry

MSigDB gene sets: 83 (showing top): REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, chr14q24, FISCHER_DREAM_TARGETS, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_TRANSCRIPTION_REPRESSOR_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GINESTIER_BREAST_CANCER_20Q13_AMPLIFICATION_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_WITH_H4K20ME1_MARK, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REPRESSOR_COMPLEX

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (0):

GO Cellular Component (2): nucleoplasm (GO:0005654), DRM complex (GO:0070176)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G0 and Early G1	2
G1/S Transition	2
Mitotic G1 phase and G1/S transition	1
G2/M Transition	1
S Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nuclear lumen	1
cellular anatomical structure	1
RNA polymerase II transcription repressor complex	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIN52	LIN54	Q6MZP7	999
LIN52	LIN37	Q96GY3	998
LIN52	LIN9	Q5TKA1	998
LIN52	RBBP4	P31149	997
LIN52	RBL2	Q08999	828
LIN52	MYBL2	P10244	815
LIN52	E2F4	Q16254	790
LIN52	E2F5	Q15329	738
LIN52	E2F2	Q14209	731
LIN52	HDAC3	O15379	677
LIN52	HDAC1	Q13547	673
LIN52	HDAC8	Q9BY41	670
LIN52	HDAC2	Q92769	666
LIN52	FOXM1	Q08050	646
LIN52	TESMIN	Q9Y4I5	625

IntAct

48 interactions, top by confidence:

A	B	Type	Score
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
LIN37	MYBL2	psi-mi:“MI:0914”(association)	0.730
LIN9	MYBL2	psi-mi:“MI:0914”(association)	0.720
LIN37	MYBL1	psi-mi:“MI:0914”(association)	0.640
LIN54	MYBL2	psi-mi:“MI:0914”(association)	0.560
RBL2	LIN52	psi-mi:“MI:0914”(association)	0.560
RBL2	LIN52	psi-mi:“MI:0915”(physical association)	0.560
EPM2AIP1	LIN52	psi-mi:“MI:0915”(physical association)	0.560
MAGEA6	LIN52	psi-mi:“MI:0915”(physical association)	0.560
LIN52	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.560
LIN52	MYBL2	psi-mi:“MI:0914”(association)	0.530
LIN9	MYBL1	psi-mi:“MI:0914”(association)	0.530
MYBL1	LIN52	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBL2	CCNE2	psi-mi:“MI:0914”(association)	0.460
Lin54	MYBL1	psi-mi:“MI:0915”(physical association)	0.400
LIN37	RPLP1	psi-mi:“MI:0914”(association)	0.350
LIN54	HDAC3	psi-mi:“MI:0914”(association)	0.350
RBL2	GSTM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): LIN52 (Affinity Capture-MS), LIN52 (Affinity Capture-MS), LIN52 (Affinity Capture-MS), LIN52 (Affinity Capture-MS), LIN52 (Affinity Capture-RNA), LIN52 (Affinity Capture-MS), LIN52 (Affinity Capture-RNA), RBL2 (Reconstituted Complex), RBL1 (Reconstituted Complex), RBL1 (Co-crystal Structure), LIN52 (Reconstituted Complex), LIN52 (Reconstituted Complex), LIN52 (Affinity Capture-Western), LIN52 (Biochemical Activity), LIN52 (Proximity Label-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: A0AUQ6, Q4RLT3, Q52LA3, Q5NVP8, Q5ZJQ3, Q6X4M3, Q8CD94

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DYRK1A	“up-regulates activity”	LIN52	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	7	175.3×	4e-13
G0 and Early G1	8	146.4×	3e-14
Transcription of E2F targets under negative control by DREAM complex	6	135.9×	1e-10
Polo-like kinase mediated events	5	132.2×	7e-09
G1/S-Specific Transcription	6	89.2×	1e-09
Cyclin E associated events during G1/S transition	7	83.3×	9e-11
Cyclin A:Cdk2-associated events at S phase entry	7	77.5×	1e-10
G1/S Transition	5	48.5×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1972 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74085571:G:GG	donor_gain	1.0000
14:74091305:AT:A	donor_gain	1.0000
14:74091307:G:GG	donor_gain	1.0000
14:74095946:A:AG	acceptor_gain	1.0000
14:74095947:G:GG	acceptor_gain	1.0000
14:74097792:A:AG	acceptor_gain	1.0000
14:74097793:G:GG	acceptor_gain	1.0000
14:74097793:GC:G	acceptor_gain	1.0000
14:74097793:GCCT:G	acceptor_gain	1.0000
14:74097858:AAGGT:A	donor_loss	1.0000
14:74097859:AGGT:A	donor_loss	1.0000
14:74097861:GT:G	donor_loss	1.0000
14:74097862:T:A	donor_loss	1.0000
14:74101237:GT:G	donor_gain	1.0000
14:74084990:GACG:G	donor_gain	0.9900
14:74085563:GAGAA:G	donor_gain	0.9900
14:74085578:GCTTT:G	donor_gain	0.9900
14:74085582:T:G	donor_gain	0.9900
14:74085582:T:TG	donor_gain	0.9900
14:74085645:GC:G	donor_gain	0.9900
14:74091206:T:TA	acceptor_gain	0.9900
14:74091212:ATCTG:A	acceptor_gain	0.9900
14:74091228:CTAG:C	acceptor_loss	0.9900
14:74091229:TA:T	acceptor_loss	0.9900
14:74091230:A:AC	acceptor_loss	0.9900
14:74091230:A:AG	acceptor_gain	0.9900
14:74091230:AG:A	acceptor_gain	0.9900
14:74091231:G:GG	acceptor_gain	0.9900
14:74091231:G:GT	acceptor_loss	0.9900
14:74091231:GG:G	acceptor_gain	0.9900

AlphaMissense

760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74091294:T:A	W32R	1.000
14:74091294:T:C	W32R	1.000
14:74091296:G:C	W32C	1.000
14:74091296:G:T	W32C	1.000
14:74101167:T:C	L75P	1.000
14:74101182:T:C	L80S	1.000
14:74101212:T:C	L90P	1.000
14:74101215:C:A	A91D	1.000
14:74101224:T:C	L94P	1.000
14:74101226:G:A	G95R	1.000
14:74101226:G:C	G95R	1.000
14:74101227:G:A	G95E	1.000
14:74101230:T:C	L96P	1.000
14:74198939:G:A	G105R	1.000
14:74198939:G:C	G105R	1.000
14:74198939:G:T	G105W	1.000
14:74198940:G:A	G105E	1.000
14:74198949:T:A	L108H	1.000
14:74198949:T:C	L108P	1.000
14:74091258:A:C	S20R	0.999
14:74091260:T:A	S20R	0.999
14:74091260:T:G	S20R	0.999
14:74091286:C:A	P29Q	0.999
14:74091295:G:C	W32S	0.999
14:74095965:T:C	F42L	0.999
14:74095967:T:A	F42L	0.999
14:74095967:T:G	F42L	0.999
14:74097818:T:A	W57R	0.999
14:74097818:T:C	W57R	0.999
14:74097855:T:C	L69S	0.999

dbSNP variants (sampled 300 via entrez): RS1000022920 (14:74166158 T>A), RS1000027612 (14:74115310 G>T), RS1000048583 (14:74138483 G>A), RS1000104554 (14:74129333 T>G), RS1000112907 (14:74122830 G>A), RS1000131454 (14:74159379 A>G), RS1000218090 (14:74123479 A>C), RS1000270341 (14:74123199 T>A,C), RS1000349594 (14:74085261 C>T), RS1000356458 (14:74152030 G>T), RS1000384017 (14:74198822 T>C), RS1000434185 (14:74165961 A>G), RS1000450073 (14:74124629 G>C), RS1000453979 (14:74116013 A>G), RS1000466764 (14:74165726 A>G)

Disease associations

OMIM: gene MIM:621288 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006976_8	Macular thickness	8.000000e-36
GCST007576_182	Chronotype	2.000000e-10
GCST008155_74	Waist-hip ratio	5.000000e-06
GCST010002_156	Refractive error	7.000000e-25
GCST90002390_273	Mean corpuscular hemoglobin	2.000000e-19
GCST90002392_461	Mean corpuscular volume	2.000000e-18
GCST90002404_351	Red cell distribution width	4.000000e-12
GCST90002404_352	Red cell distribution width	1.000000e-29
GCST90002404_400	Red cell distribution width	4.000000e-26

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004343	waist-hip ratio
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

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	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
abrine	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Coumestrol	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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