LIN28B

Summary

LIN28B (lin-28 RNA binding posttranscriptional regulator B, HGNC:32207) is a protein-coding gene on chromosome 6q16.3-q21, encoding Protein lin-28 homolog B (Q6ZN17). Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c.

The protein encoded by this gene belongs to the lin-28 family, which is characterized by the presence of a cold-shock domain and a pair of CCHC zinc finger domains. This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines. It is negatively regulated by microRNAs that target sites in the 3’ UTR, and overexpression of this gene in primary tumors is linked to the repression of let-7 family of microRNAs and derepression of let-7 targets, which facilitates cellular transformation.

Source: NCBI Gene 389421 — RefSeq curated summary.

At a glance

• GWAS associations: 87
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes
• MANE Select transcript: NM_001004317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32207
Approved symbol	LIN28B
Name	lin-28 RNA binding posttranscriptional regulator B
Location	6q16.3-q21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16517, CSDD2
Ensembl gene	ENSG00000187772
Ensembl biotype	protein_coding
OMIM	611044
Entrez	389421

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000345080, ENST00000635857, ENST00000637759

RefSeq mRNA: 2 — MANE Select: NM_001004317 NM_001004317, NM_001410939

CCDS: CCDS34504, CCDS93980

Canonical transcript exons

ENST00000345080 — 4 exons

Exon	Start	End
ENSE00001373844	105026298	105026482
ENSE00001375518	104958099	104958286
ENSE00001381591	105078414	105083332
ENSE00001428389	104957107	104957260

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 95.85.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1933 / max 320.5078, expressed in 351 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69050	1.0262	229
69043	0.7742	172
69049	0.5660	232
69042	0.5106	22
69045	0.4341	146
69051	0.2160	126
69041	0.2049	21
69044	0.1991	117
69046	0.1439	89
69052	0.1183	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	95.85	gold quality
buccal mucosa cell	CL:0002336	91.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.48	gold quality
secondary oocyte	CL:0000655	81.36	gold quality
adrenal tissue	UBERON:0018303	73.42	gold quality
sperm	CL:0000019	72.03	gold quality
decidua	UBERON:0002450	70.88	gold quality
oocyte	CL:0000023	64.86	gold quality
ileal mucosa	UBERON:0000331	60.92	silver quality
Brodmann (1909) area 23	UBERON:0013554	60.70	gold quality
testis	UBERON:0000473	60.41	gold quality
right testis	UBERON:0004534	58.29	gold quality
cortical plate	UBERON:0005343	57.16	gold quality
left testis	UBERON:0004533	57.10	gold quality
primary visual cortex	UBERON:0002436	55.26	gold quality
pancreatic ductal cell	CL:0002079	54.64	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.00	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
tibialis anterior	UBERON:0001385	53.07	silver quality
endothelial cell	CL:0000115	52.02	gold quality
occipital lobe	UBERON:0002021	51.39	silver quality
prefrontal cortex	UBERON:0000451	50.67	gold quality
adult organism	UBERON:0007023	50.38	silver quality
myocardium	UBERON:0002349	50.25	gold quality
deltoid	UBERON:0001476	50.09	gold quality
ganglionic eminence	UBERON:0004023	49.77	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43
E-CURD-53	no	184.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DACH1, LAMTOR5, MYC, TBP

miRNA regulators (miRDB)

300 targeting LIN28B, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408

Literature-anchored findings (GeneRIF, showing 40)

• These findings strongly implicate a critical role of LIN28B during development and tumorigenesis and suggest a possible novel mechanism. (PMID:16971064)
• highlight an important role for Lin-28B in Myc-driven cellular phenotypes (PMID:19211792)
• Variation in LIN28B, a potent and specific regulator of microRNA processing is the first genetic determinant regulating the timing of human pubertal growth and development. (PMID:19448623)
• Study shows that LIN28 and LIN28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency approximately 15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. (PMID:19483683)
• N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b (PMID:19495417)
• LIN28B plays an important role in radiation responses of lung cancer cells through inhibiting let-7g microRNA processing and increasing translation of KRAS. (PMID:19745602)
• A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure. (PMID:20303062)
• Lack of any variation in the coding region of the gene suggests that LIN28B in developmental timing is so crucial that any changes in the conserved protein would probably be lethal (PMID:20350940)
• Distinct variants at LIN28B influence growth in height from birth to adulthood. (PMID:20398887)
• High Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma. (PMID:20525879)
• MicroRNA-125b exerts tumor-suppressive effects in hepatic carcinogenesis through the suppression of oncogene LIN28B expression. (PMID:20827722)
• A common genetic variant in LIN28B that confers earlier puberty was associated with a prolonged increase in BMI during adolescence and early to mid-adulthood in women only. (PMID:20962026)
• findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis. (PMID:21512136)
• reported interaction between LIN28B and Let-7 was recapitulated by siRNA knockdown in ovarian cancer cell lines (PMID:21533284)
• findings establish a new role for LIN28B in human colon cancer pathogenesis, and suggest LIN28B post-transcriptionally regulates LGR5 and PROM1 through a let-7-independent mechanism (PMID:21625210)
• Unlike Lin28A, Lin28B represses let-7 processing through a Zcchc11-independent mechanism; Lin28B functions in the nucleus by sequestering primary let-7 transcripts and inhibiting their processing by the Microprocessor. (PMID:22118463)
• Both HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b could express Lin28a and Lin28b effectively. (PMID:22263265)
• High expression of Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. (PMID:22433967)
• High lin-28B expression is associated with epithelial ovarian cancer. (PMID:22822098)
• common variants in HACE1 and LIN28B influence neuroblastoma susceptibility and indicate that both genes likely have a role in disease progression. (PMID:22941191)
• Although LIN28B SNPs were associated with normal pubertal timing, rare variations in this gene do not seem to be commonly involved in the molecular pathogenesis of CPP. (PMID:22964795)
• Rpl22 inactivation promotes neoplastic transformation by inducing expression of Lin28B (PMID:22976955)
• LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. (PMID:23042116)
• We find that LIN28B rs314277 is associated with significant recurrence of colorectal cancer in Stage II disease. (PMID:23052130)
• Data indicate that full length Lin28B is required to bind efficiently to pre-let-7g. (PMID:23063642)
• Genetic variants near the puberty-associated gene LIN28B associate with adult weight and body shape in females, suggesting that the gene may tag molecular pathways influencing adult adiposity-related traits. (PMID:23152804)
• Lin28A/Lin28B serves as key driver genes in Hepatitis B virus X protein-induced hepatocarcinogenesis (PMID:23318446)
• Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. (PMID:23378032)
• Report role of Lin28b/IGF signaling pathway in the progression of head and neck neoplasms. (PMID:23482325)
• The oncoprotein HBXIP upregulates Lin28B via activating TF II D to promote proliferation of breast cancer cells. (PMID:23494474)
• MYCN/LIN28B/Let-7/HMGA2 pathway implicated by meta-analysis of GWAS in suppression of post-natal proliferation thereby potentially contributing to aging (PMID:23639551)
• These data confirm the strongest gene reported in Europeans (LIN28B) as a contributor to age of menarche in an Asian population. (PMID:23740805)
• LIN28B expression regulates HbF levels and causes adult human erythroblasts to differentiate with a more fetal-like phenotype (PMID:23798711)
• miR-26a directly targets Lin28B and Zcchc11-two critical repressors of let-7 maturation. (PMID:24056962)
• Lin28B is an oncofetal circulating cancer stem cell-like marker associated with recurrence of hepatocellular carcinoma. (PMID:24244607)
• Lin28B is a novel marker for predicting prognosis in patients with oral squamous cell carcinoma (PMID:24386298)
• reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation (PMID:24498170)
• Consistent with the let-7 microRNA stimulatory role of TRIM71 via Lin28B polyubiquitination. (PMID:24602972)
• demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor (PMID:24732380)
• Genetic variants of LIN28B may be biomarkers for susceptibility to severe radiation pneumonitis in non-small cell lung cancer patients. (PMID:24780874)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	lin28b	ENSDARG00000052511
mus_musculus	Lin28b	ENSMUSG00000063804
rattus_norvegicus	Lin28b	ENSRNOG00000025938
drosophila_melanogaster	lin-28	FBGN0035626
caenorhabditis_elegans	cey-2	WBGENE00000473
caenorhabditis_elegans	cey-3	WBGENE00000474
caenorhabditis_elegans		WBGENE00000475

Paralogs (4): YBX2 (ENSG00000006047), YBX3 (ENSG00000060138), YBX1 (ENSG00000065978), LIN28A (ENSG00000131914)

Protein

Protein identifiers

Protein lin-28 homolog B — Q6ZN17 (reviewed: Q6ZN17)

All UniProt accessions (3): A0A1B0GTK2, A0A1B0GVD3, Q6ZN17

UniProt curated annotations — full annotation on UniProt →

Function. Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA. Does not act on pri-miR21. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation. This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent. Interaction with target pre-miRNAs occurs via an 5’-GGAG-3’ motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression. When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Expressed at high levels in the placenta and, at mucher lower, in testis and fetal liver. Isoform 1 is only detected in placenta and in moderately and poorly differentiated hepatocellular carcinoma cells (at protein level). Isoform 2 is detected in fetal liver, non-tumor liver tissues, as well as well-differentiated tumor tissues (at protein level). Tends to be up-regulated in triple-negative (ER-,PR-,HER2-) breast tumors, as well as in liver, ovarian, and thyroid carcinomas.

Domain organisation. The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids.

Induction. Might be negatively regulated by the microRNA let-7b.

Similarity. Belongs to the lin-28 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZN17-1	1	yes
Q6ZN17-2	2, LIN28BS

RefSeq proteins (2): NP_001004317, NP_001397868 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR002059	CSP_DNA-bd	Domain
IPR011129	CSD	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR051373	Lin-28_RNA-binding	Family
IPR054081	Lin-28A-like_Znf-CCHC_2	Domain

Pfam: PF00098, PF00313, PF21890

UniProt features (36 total): binding site 8, strand 6, modified residue 5, compositionally biased region 4, region of interest 3, zinc finger region 2, helix 2, short sequence motif 2, chain 1, domain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4A4I	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZN17-F1	73.94	0.37

Functional residue map

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

Ligand- & substrate-binding residues (8): 129; 132; 137; 142; 151; 154; 159; 164

Post-translational modifications (5): 54, 96, 105, 110, 203

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 278 (showing top): ACTACCT_MIR196A_MIR196B, GTCTACC_MIR379, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, AGTCTTA_MIR499, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, ATTACAT_MIR3803P, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_PRE_MIRNA_PROCESSING, CONRAD_STEM_CELL, TGCCTTA_MIR124A, CAGCCTC_MIR4855P, SENESE_HDAC3_TARGETS_DN

GO Biological Process (9): miRNA catabolic process (GO:0010587), pre-miRNA processing (GO:0031054), RNA 3’-end processing (GO:0031123), RNA destabilization (GO:0050779), positive regulation of miRNA catabolic process (GO:2000627), negative regulation of pre-miRNA processing (GO:2000632), negative regulation of primary miRNA processing (GO:2000635), post-transcriptional regulation of gene expression (GO:0010608), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA catabolic process	2
positive regulation of catabolic process	2
negative regulation of miRNA processing	2
binding	2
nuclear lumen	2
miRNA metabolic process	1
miRNA processing	1
RNA processing	1
regulation of RNA stability	1
positive regulation of RNA metabolic process	1
miRNA catabolic process	1
regulation of miRNA catabolic process	1
positive regulation of miRNA metabolic process	1
pre-miRNA processing	1
regulation of pre-miRNA processing	1
primary miRNA processing	1
regulation of primary miRNA processing	1
regulation of gene expression	1
negative regulation of gene expression	1
nucleic acid binding	1
RNA binding	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIN28B	TUT4	Q5TAX3	925
LIN28B	F5H6H0	F5H6H0	822
LIN28B	DROSHA	Q9NRR4	797
LIN28B	DICER1	Q9UPY3	767
LIN28B	DPPA3	Q6W0C5	745
LIN28B	IGF2BP1	Q9NZI8	734
LIN28B	SOX2	P48431	714
LIN28B	MYC	P01106	697
LIN28B	TUT1	Q9H6E5	691
LIN28B	POU5F1	P31359	690
LIN28B	NANOG	Q9H9S0	684
LIN28B	ADGRD1	Q6QNK2	682
LIN28B	ADGRG6	Q86SQ4	667
LIN28B	SBF2	Q86WG5	649
LIN28B	IGF2BP3	O00425	646

IntAct

76 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.770
LIN28B		psi-mi:“MI:0414”(enzymatic reaction)	0.540
LIN28B		psi-mi:“MI:0915”(physical association)	0.540
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
ZC3H8	RSL1D1	psi-mi:“MI:0914”(association)	0.530
ZBTB24	CBX6	psi-mi:“MI:0914”(association)	0.530
LIN28B	ZBTB24	psi-mi:“MI:0914”(association)	0.530
HNRNPC	CASC3	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
DAXX	SIN3B	psi-mi:“MI:0914”(association)	0.530
REXO4	CASC3	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
LIN28B		psi-mi:“MI:0414”(enzymatic reaction)	0.440
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
k8	RGL2	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
SURF2	KPNA6	psi-mi:“MI:0914”(association)	0.350
ZC3HAV1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
USP36	STK25	psi-mi:“MI:0914”(association)	0.350
SRPK2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
LIN28A	AGPS	psi-mi:“MI:0914”(association)	0.350

BioGRID (267): LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Affinity Capture-MS), LIN28B (Proximity Label-MS)

ESM2 similar proteins: A2AGX3, A4Q9F3, A6QPH9, D3YYI7, E9PGG2, P29590, Q0P5B4, Q0VC73, Q2TBI2, Q3T0G1, Q45KJ4, Q45KJ6, Q4R7H0, Q5BJT4, Q5E9N3, Q5NVM3, Q5PPH4, Q5U208, Q5XI57, Q642B6, Q6P3Z3, Q6P9L4, Q6ZN17, Q6ZVT0, Q70EL4, Q7L4P6, Q8AVK2, Q8BJ25, Q8BUM9, Q8C6D4, Q8CDF7, Q8CE64, Q8CHW1, Q8N554, Q8NA92, Q8NFT6, Q8TC41, Q8VCZ3, Q8WTV1, Q8WY91

Diamond homologs: B5DE31, E0J1Q3, E0J500, E1WGN1, O30875, O54310, O65639, O67327, P0A355, P0A356, P0A357, P0A358, P0A361, P0A362, P0A363, P0A972, P0A973, P0A974, P0A975, P0A978, P0A979, P0A980, P0A981, P0A986, P0A987, P0A9X9, P0A9Y0, P0A9Y1, P0A9Y2, P0A9Y3, P0A9Y4, P0A9Y5, P0A9Y6, P0A9Y7, P0A9Y8, P0A9Y9, P0A9Z0, P0C0F1, P0CL01, P0DA48

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
LAMTOR5	“up-regulates quantity by expression”	LIN28B	“transcriptional regulation”
TBP	“up-regulates quantity by expression”	LIN28B	“transcriptional regulation”
TRIM71	“down-regulates quantity by destabilization”	LIN28B	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
Processing of Capped Intron-Containing Pre-mRNA	8	12.4×	5e-05
mRNA Polyadenylation	7	11.6×	2e-04
mRNA Splicing - Major Pathway	8	8.2×	4e-04
Major pathway of rRNA processing in the nucleolus and cytosol	7	8.2×	1e-03
Translation	6	7.0×	7e-03
Dengue Virus-Host Interactions	8	6.9×	1e-03
Metabolism of RNA	8	6.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
rRNA processing	9	15.5×	2e-06
ribosomal small subunit biogenesis	5	13.9×	4e-03
translation	7	8.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
981211	GRCh37/hg19 6q16.1-21(chr6:98949950-114533905)x1	Pathogenic

SpliceAI

1535 predictions. Top by Δscore:

Variant	Effect	Δscore
6:104957205:A:T	donor_gain	1.0000
6:104958094:CTCA:C	acceptor_loss	1.0000
6:104958095:TCAG:T	acceptor_loss	1.0000
6:104958096:CAG:C	acceptor_loss	1.0000
6:104958097:A:AG	acceptor_gain	1.0000
6:104958097:A:C	acceptor_loss	1.0000
6:104958097:AGGC:A	acceptor_gain	1.0000
6:104958097:AGGCG:A	acceptor_gain	1.0000
6:104958098:G:A	acceptor_loss	1.0000
6:104958098:G:GG	acceptor_gain	1.0000
6:104958098:GGC:G	acceptor_gain	1.0000
6:104958098:GGCG:G	acceptor_gain	1.0000
6:104958098:GGCGG:G	acceptor_gain	1.0000
6:104958287:G:GG	donor_gain	1.0000
6:105026277:A:AG	acceptor_gain	1.0000
6:105026278:C:G	acceptor_gain	1.0000
6:105026286:T:TA	acceptor_gain	1.0000
6:105026293:TACA:T	acceptor_loss	1.0000
6:105026293:TACAG:T	acceptor_gain	1.0000
6:105026294:A:AG	acceptor_gain	1.0000
6:105026294:ACAG:A	acceptor_loss	1.0000
6:105026294:ACAGA:A	acceptor_gain	1.0000
6:105026295:C:G	acceptor_gain	1.0000
6:105026295:CA:C	acceptor_loss	1.0000
6:105026295:CAG:C	acceptor_gain	1.0000
6:105026296:A:AG	acceptor_gain	1.0000
6:105026296:A:AT	acceptor_loss	1.0000
6:105026296:AGA:A	acceptor_gain	1.0000
6:105026297:G:A	acceptor_loss	1.0000
6:105026297:G:C	acceptor_gain	1.0000

AlphaMissense

1622 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:104958183:G:A	G32D	1.000
6:104958189:G:A	C34Y	1.000
6:104958190:T:G	C34W	1.000
6:104958194:T:A	W36R	1.000
6:104958194:T:C	W36R	1.000
6:104958196:G:C	W36C	1.000
6:104958196:G:T	W36C	1.000
6:104958197:T:A	F37I	1.000
6:104958197:T:C	F37L	1.000
6:104958197:T:G	F37V	1.000
6:104958198:T:C	F37S	1.000
6:104958198:T:G	F37C	1.000
6:104958199:C:A	F37L	1.000
6:104958199:C:G	F37L	1.000
6:104958202:T:A	N38K	1.000
6:104958202:T:G	N38K	1.000
6:104958212:G:A	G42R	1.000
6:104958212:G:C	G42R	1.000
6:104958213:G:A	G42E	1.000
6:104958215:T:A	F43I	1.000
6:104958215:T:C	F43L	1.000
6:104958215:T:G	F43V	1.000
6:104958216:T:C	F43S	1.000
6:104958216:T:G	F43C	1.000
6:104958217:T:A	F43L	1.000
6:104958217:T:G	F43L	1.000
6:104958218:G:A	G44R	1.000
6:104958218:G:C	G44R	1.000
6:104958219:G:A	G44E	1.000
6:104958219:G:T	G44V	1.000

dbSNP variants (sampled 300 via entrez): RS1000053999 (6:104949521 G>A), RS1000055685 (6:104950019 T>G), RS1000102274 (6:105033537 G>A), RS1000103453 (6:104949908 T>C), RS1000106396 (6:105030012 CTG>C), RS1000108298 (6:104942202 A>G), RS1000110227 (6:105083698 T>G), RS1000191093 (6:105051040 C>A,G,T), RS1000197905 (6:105055295 A>G), RS1000224164 (6:104957567 G>T), RS1000274816 (6:105043414 T>C), RS1000276608 (6:104957852 G>A,C,T), RS1000282899 (6:104996318 T>A), RS1000304526 (6:104993389 G>A,C), RS1000321729 (6:105036194 T>A)

Disease associations

OMIM: gene MIM:611044 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000520	Proptosis
HP:0000737	Irritability
HP:0000822	Hypertension
HP:0001017	Anemic pallor
HP:0001251	Ataxia
HP:0001336	Myoclonus
HP:0001482	Subcutaneous nodule
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001928	Abnormality of coagulation
HP:0001945	Fever
HP:0002028	Chronic diarrhea
HP:0002098	Respiratory distress
HP:0002176	Spinal cord compression
HP:0002277	Horner syndrome
HP:0002653	Bone pain
HP:0002716	Lymphadenopathy
HP:0002756	Pathologic fracture
HP:0003006	Neuroblastoma
HP:0003270	Abdominal distention
HP:0003281	Increased circulating ferritin concentration
HP:0003334	Elevated circulating catecholamine level
HP:0004375	Neoplasm of the nervous system
HP:0010543	Opsoclonus
HP:0011976	Elevated urinary catecholamine level
HP:0011977	Elevated urinary homovanillic acid
HP:0011978	Elevated urinary vanillylmandelic acid
HP:0012378	Fatigue

GWAS associations

87 associations (top):

Study	Trait	p-value
GCST000175_14	Height	8.000000e-07
GCST000176_10	Height	1.000000e-08
GCST000400_1	Menarche (age at onset)	2.000000e-14
GCST000403_3	Menarche and menopause (age at onset)	3.000000e-13
GCST000404_2	Menarche (age at onset)	7.000000e-09
GCST000405_1	Menarche (age at onset)	4.000000e-16
GCST000630_1	Digit length ratio	2.000000e-06
GCST000817_108	Height	8.000000e-31
GCST000880_37	Menarche (age at onset)	5.000000e-60
GCST001660_6	Neuroblastoma	1.000000e-08
GCST001876_1	Pubertal anthropometrics	4.000000e-09
GCST001876_13	Pubertal anthropometrics	2.000000e-07
GCST001956_70	Height	5.000000e-12
GCST002013_1	Menarche (age at onset)	5.000000e-07
GCST002425_2	Puberty onset	2.000000e-08
GCST002427_1	Puberty onset (breast development)	3.000000e-07
GCST002541_54	Menarche (age at onset)	6.000000e-59
GCST002541_55	Menarche (age at onset)	8.000000e-110
GCST002647_57	Height	1.000000e-42
GCST002702_121	Height	5.000000e-08
GCST003993_1	Menarche (age at onset)	4.000000e-57
GCST003994_8	Age at voice drop	1.000000e-23
GCST004063_29	Waist circumference adjusted for body mass index	2.000000e-06
GCST004063_84	Waist circumference adjusted for body mass index	2.000000e-12
GCST004063_9	Waist circumference adjusted for body mass index	1.000000e-15
GCST004067_111	Hip circumference adjusted for BMI	2.000000e-13
GCST004067_149	Hip circumference adjusted for BMI	1.000000e-09
GCST004067_42	Hip circumference adjusted for BMI	2.000000e-06
GCST004253_9	Accelerated cognitive decline after conversion of mild cognitive impairment to Alzheimer’s disease (Alzhiemer’s diagnosis trajectory interaction)	5.000000e-06
GCST004500_106	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-14

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004841	digit length ratio
EFO:0001382	puberty
EFO:0005677	puberty onset measurement
EFO:0007888	age at voice drop
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0007710	cognitive decline measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0004341	body fat distribution
EFO:0010459	aminoadipic acid measurement
EFO:0010493	glycodeoxycholate measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4295873 (SINGLE PROTEIN), CHEMBL4523614 (PROTEIN FAMILY)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
Valproic Acid	decreases expression	3
Benzo(a)pyrene	affects methylation	2
Tetrachlorodibenzodioxin	decreases expression	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
arsenite	increases methylation	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	affects expression, increases reaction, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Panobinostat	affects expression, increases reaction, decreases expression	1
Arsenic	increases methylation	1
Vehicle Emissions	decreases expression, increases expression, affects reaction	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Malathion	increases expression	1
Methapyrilene	increases methylation	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4150507	Binding	Binding affinity to human N-terminal Halo-fused/biotin-labelled Lin28B expressed in Escherichia coli BL21(DE3) assessed as inhibition of protein interaction with pre-Let-7d microRNA measured after 1 hr by cat-ELCCA	Expansion of cat-ELCCA for the Discovery of Small Molecule Inhibitors of the Pre-let-7-Lin28 RNA-Protein Interaction. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3A6	Abcam HEK293T LIN28B KO	Transformed cell line	Female
CVCL_B8JT	Abcam HCT 116 LIN28B KO	Cancer cell line	Male
CVCL_B9M2	Abcam A-549 LIN28B KO	Cancer cell line	Male
CVCL_C3NF	A2780 LIN28B KO	Cancer cell line	Female
CVCL_D2G9	Abcam MCF-7 LIN28B KO	Cancer cell line	Female
CVCL_F1QG	HyCyte HGC-27 KO-hLIN28B	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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