LIN37

Summary

LIN37 (lin-37 DREAM MuvB core complex component, HGNC:33234) is a protein-coding gene on chromosome 19q13.12, encoding Protein lin-37 homolog (Q96GY3).

This gene encodes a protein expressed in the eye.

Source: NCBI Gene 55957 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_019104

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33234
Approved symbol	LIN37
Name	lin-37 DREAM MuvB core complex component
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	ZK418.4, F25965, lin-37
Ensembl gene	ENSG00000267796
Ensembl biotype	protein_coding
OMIM	621287
Entrez	55957

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000301159, ENST00000587108, ENST00000587751, ENST00000590706, ENST00000590890, ENST00000591076, ENST00000591163, ENST00000592871, ENST00000595455, ENST00000894507, ENST00000894508

RefSeq mRNA: 2 — MANE Select: NM_019104 NM_001369780, NM_019104

CCDS: CCDS62642

Canonical transcript exons

ENST00000301159 — 9 exons

Exon	Start	End
ENSE00003483538	35752914	35752999
ENSE00003501814	35754246	35754319
ENSE00003506781	35752804	35752833
ENSE00003548573	35752434	35752484
ENSE00003611199	35752176	35752251
ENSE00003642748	35753087	35753253
ENSE00003674480	35754017	35754157
ENSE00003684558	35754393	35754519
ENSE00003688761	35748576	35748758

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 91.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4741 / max 62.0868, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175387	5.2818	1731
175386	5.0966	1681
175388	0.0957	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	91.14	gold quality
cerebellar hemisphere	UBERON:0002245	90.88	gold quality
cerebellar cortex	UBERON:0002129	90.83	gold quality
right ovary	UBERON:0002118	90.55	gold quality
left ovary	UBERON:0002119	90.01	gold quality
granulocyte	CL:0000094	89.94	gold quality
adenohypophysis	UBERON:0002196	89.86	gold quality
left uterine tube	UBERON:0001303	89.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.81	gold quality
cerebellum	UBERON:0002037	89.63	gold quality
popliteal artery	UBERON:0002250	89.34	gold quality
tibial artery	UBERON:0007610	89.33	gold quality
aorta	UBERON:0000947	88.71	gold quality
right frontal lobe	UBERON:0002810	88.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.66	gold quality
mucosa of stomach	UBERON:0001199	88.64	gold quality
descending thoracic aorta	UBERON:0002345	88.30	gold quality
prefrontal cortex	UBERON:0000451	88.25	gold quality
apex of heart	UBERON:0002098	88.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.14	gold quality
lower esophagus	UBERON:0013473	88.11	gold quality
thoracic aorta	UBERON:0001515	88.04	gold quality
anterior cingulate cortex	UBERON:0009835	88.03	gold quality
pituitary gland	UBERON:0000007	87.99	gold quality
body of uterus	UBERON:0009853	87.96	gold quality
ascending aorta	UBERON:0001496	87.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.83	gold quality
nucleus accumbens	UBERON:0001882	87.59	gold quality
left coronary artery	UBERON:0001626	87.56	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.32

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Abrogation of DREAM function by knockout of the DREAM component LIN37 results in a reduced repression of cell-cycle genes. (PMID:31400114)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lin37	ENSDARG00000053950
mus_musculus	Lin37	ENSMUSG00000036845
rattus_norvegicus	Lin37	ENSRNOG00000020929
drosophila_melanogaster	mip40	FBGN0034430

Protein

Protein identifiers

Protein lin-37 homolog — Q96GY3 (reviewed: Q96GY3)

Alternative names: Antolefinin

All UniProt accessions (4): Q96GY3, K7ELP2, K7EMY4, M0QYM3

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.

RefSeq proteins (2): NP_001356709, NP_061977* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028226	LIN37	Family

Pfam: PF15306

UniProt features (19 total): modified residue 6, region of interest 2, cross-link 2, sequence variant 2, strand 2, helix 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7N40	X-RAY DIFFRACTION	2.55
7R1D	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GY3-F1	71.04	0.30

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 (8): 202, 5, 7, 1, 135, 138, 167, 182

Function

Pathways and Gene Ontology

Reactome pathways

14 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
R-HSA-1640170	Cell Cycle
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69206	G1/S Transition
R-HSA-69242	S Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 119 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, BROWNE_HCMV_INFECTION_16HR_UP, BROWNE_HCMV_INFECTION_12HR_UP, MODULE_285, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, AACTTT_UNKNOWN, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, TCCCRNNRTGC_UNKNOWN, GOCC_TRANSCRIPTION_REPRESSOR_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOBP_CELL_CYCLE_PROCESS, KIM_WT1_TARGETS_DN

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), gene expression (GO:0010467), G0 to G1 transition (GO:0045023)

GO Molecular Function (2): protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053), Myb complex (GO:0031523)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Cell Cycle, Mitotic	3
G0 and Early G1	2
Mitotic G1 phase and G1/S transition	2
G1/S Transition	2
G2/M Transition	1
S Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
macromolecule biosynthetic process	1
cell cycle process	1
nuclear lumen	1
cellular anatomical structure	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

812 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIN37	RBBP4	P31149	999
LIN37	LIN9	Q5TKA1	999
LIN37	LIN54	Q6MZP7	999
LIN37	LIN52	Q52LA3	998
LIN37	MYBL2	P10244	978
LIN37	E2F4	Q16254	899
LIN37	RBL2	Q08999	867
LIN37	E2F5	Q15329	691
LIN37	FOXM1	Q08050	681
LIN37	MSI1	O43347	665
LIN37	DPP6	P42658	648
LIN37	TESMIN	Q9Y4I5	541
LIN37	RBBP7	Q16576	531
LIN37	S100A7	P31151	496
LIN37	TPRG1L	Q5T0D9	490

IntAct

92 interactions, top by confidence:

A	B	Type	Score
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
LIN37	RBL2	psi-mi:“MI:0914”(association)	0.770
RBL2	LIN37	psi-mi:“MI:0915”(physical association)	0.770
LIN37	MYBL2	psi-mi:“MI:0914”(association)	0.730
LIN37	MAGEA6	psi-mi:“MI:0915”(physical association)	0.720
MAGEA6	LIN37	psi-mi:“MI:0915”(physical association)	0.720
LIN9	MYBL2	psi-mi:“MI:0914”(association)	0.720
LIN9	RBL2	psi-mi:“MI:0914”(association)	0.700
RBL2	LIN9	psi-mi:“MI:0914”(association)	0.700
LIN37	MYBL1	psi-mi:“MI:0914”(association)	0.640
LIN54	RBL2	psi-mi:“MI:0914”(association)	0.620
CDR2	LIN37	psi-mi:“MI:0915”(physical association)	0.560
KRT31	LIN37	psi-mi:“MI:0915”(physical association)	0.560
LIN37	KRT40	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	LIN37	psi-mi:“MI:0915”(physical association)	0.560
LIN37	CEP70	psi-mi:“MI:0915”(physical association)	0.560
LIN37	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
LIN37	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
LIN37	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
LIN37	TFIP11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (162): LIN37 (Two-hybrid), LIN37 (Two-hybrid), LIN37 (Two-hybrid), LIN37 (Two-hybrid), LIN37 (Two-hybrid), LIN37 (Two-hybrid), TRIM54 (Two-hybrid), CEP70 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), LIN37 (Affinity Capture-MS), LIN54 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), MYBL1 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTI1, A2BIL8, A5PKK9, C5DY61, E2QSX5, E7F555, O35147, O43151, P11805, P19416, P24940, P27579, Q06616, Q17QE3, Q1LZE2, Q1RMQ5, Q1T763, Q28CW2, Q2HR82, Q2TBN9, Q3B8E9, Q3ZBS1, Q567C6, Q5RDK8, Q62417, Q68FW2, Q6AY26, Q6DFB0, Q6P6I6, Q6PKN7, Q80U49, Q86YL5, Q8C3W1, Q8QVM1, Q8VEB3, Q8VI59, Q96FT9, Q96GV9, Q96GY3, Q99618

Diamond homologs: Q1RMQ5, Q96GY3, Q9D8N6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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
Polo-like kinase mediated events	6	135.9×	2e-10
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	6	128.8×	2e-10
G0 and Early G1	8	125.5×	1e-13
Transcription of E2F targets under negative control by DREAM complex	6	116.5×	3e-10
Cyclin E associated events during G1/S transition	7	71.4×	2e-10
Cyclin A:Cdk2-associated events at S phase entry	7	66.4×	3e-10
G1/S-Specific Transcription	5	63.7×	4e-07
Mitotic G1 phase and G1/S transition	5	32.9×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1176 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35752174:A:AG	acceptor_gain	1.0000
19:35752175:G:GG	acceptor_gain	1.0000
19:35752175:GA:G	acceptor_gain	1.0000
19:35752248:ACAGG:A	donor_loss	1.0000
19:35752249:CAGG:C	donor_loss	1.0000
19:35752250:AG:A	donor_loss	1.0000
19:35752251:GGTA:G	donor_loss	1.0000
19:35752252:G:T	donor_loss	1.0000
19:35752253:T:G	donor_loss	1.0000
19:35752428:CTCTA:C	acceptor_loss	1.0000
19:35752429:TCTA:T	acceptor_loss	1.0000
19:35752430:CTA:C	acceptor_loss	1.0000
19:35752431:TA:T	acceptor_loss	1.0000
19:35752432:A:AG	acceptor_gain	1.0000
19:35752432:A:C	acceptor_loss	1.0000
19:35752433:G:GG	acceptor_gain	1.0000
19:35752433:GGGA:G	acceptor_gain	1.0000
19:35752481:A:AG	donor_gain	1.0000
19:35752481:A:G	donor_gain	1.0000
19:35752482:TAA:T	donor_gain	1.0000
19:35752485:G:GG	donor_gain	1.0000
19:35752802:A:C	acceptor_loss	1.0000
19:35752803:G:A	acceptor_loss	1.0000
19:35752911:C:CA	acceptor_gain	1.0000
19:35753083:CCAG:C	acceptor_loss	1.0000
19:35753084:CAG:C	acceptor_loss	1.0000
19:35753085:A:AG	acceptor_gain	1.0000
19:35753085:AGAC:A	acceptor_loss	1.0000
19:35753086:G:GA	acceptor_gain	1.0000
19:35753086:G:GC	acceptor_gain	1.0000

AlphaMissense

1605 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35753173:T:A	W122R	1.000
19:35753173:T:C	W122R	1.000
19:35753175:G:C	W122C	1.000
19:35753175:G:T	W122C	1.000
19:35754300:T:A	W214R	1.000
19:35754300:T:C	W214R	1.000
19:35754302:G:C	W214C	1.000
19:35754302:G:T	W214C	1.000
19:35753107:T:C	F100L	0.999
19:35753109:C:A	F100L	0.999
19:35753109:C:G	F100L	0.999
19:35753114:G:C	R102P	0.999
19:35753126:T:C	L106S	0.999
19:35753134:T:C	F109L	0.999
19:35753136:C:A	F109L	0.999
19:35753136:C:G	F109L	0.999
19:35753155:T:G	Y116D	0.999
19:35753156:A:G	Y116C	0.999
19:35753164:T:C	C119R	0.999
19:35753165:G:A	C119Y	0.999
19:35753166:C:G	C119W	0.999
19:35753174:G:C	W122S	0.999
19:35754301:G:C	W214S	0.999
19:35754394:T:A	W221R	0.999
19:35754394:T:C	W221R	0.999
19:35754436:A:C	S235R	0.999
19:35754438:C:A	S235R	0.999
19:35754438:C:G	S235R	0.999
19:35752218:T:C	L26S	0.998
19:35753105:T:C	L99P	0.998

dbSNP variants (sampled 300 via entrez): RS1000515261 (19:35748030 C>G), RS1000870939 (19:35752664 T>C), RS1001123270 (19:35746666 C>A), RS1001557618 (19:35751689 C>T), RS1002334305 (19:35752122 C>A,T), RS1002611132 (19:35749394 C>T), RS1002795221 (19:35752361 T>G), RS1002980924 (19:35749058 T>A), RS1003360502 (19:35749344 T>G), RS1003743086 (19:35750537 A>G), RS1004310566 (19:35752072 G>A), RS1004341592 (19:35751687 C>T), RS1004645277 (19:35750305 G>A), RS1004646415 (19:35753446 G>A,T), RS1004672705 (19:35753112 C>A)

Disease associations

OMIM: gene MIM:621287 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010002_54	Refractive error	1.000000e-10
GCST010703_277	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	3
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
bisphenol S	decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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