LENG8

Summary

LENG8 (leukocyte receptor cluster member 8, HGNC:15500) is a protein-coding gene on chromosome 19q13.42, encoding Leukocyte receptor cluster member 8 (Q96PV6). It is a selective cancer dependency (DepMap: 48.8% of cell lines).

Predicted to be part of protein-containing complex. Predicted to be active in nucleus.

Source: NCBI Gene 114823 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 169 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 48.8% of screened cell lines
• MANE Select transcript: NM_052925

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15500
Approved symbol	LENG8
Name	leukocyte receptor cluster member 8
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1932, MGC40108, pp13842
Ensembl gene	ENSG00000167615
Ensembl biotype	protein_coding
OMIM	616575
Entrez	114823

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000326764, ENST00000376514, ENST00000421200, ENST00000436479, ENST00000439657, ENST00000443957, ENST00000462541, ENST00000610347, ENST00000886965, ENST00000886966, ENST00000886967, ENST00000886968

RefSeq mRNA: 6 — MANE Select: NM_052925 NM_001375638, NM_001375639, NM_001375640, NM_001375641, NM_001411063, NM_052925

CCDS: CCDS12894, CCDS92685, CCDS92686

Canonical transcript exons

ENST00000326764 — 16 exons

Exon	Start	End
ENSE00001269325	54460766	54462016
ENSE00002429875	54458314	54458521
ENSE00002458885	54453546	54453656
ENSE00003907153	54449199	54449310
ENSE00004013834	54456325	54456465
ENSE00004013835	54452093	54452267
ENSE00004013836	54454430	54454682
ENSE00004013837	54451290	54451382
ENSE00004013838	54457747	54457848
ENSE00004013839	54454951	54455092
ENSE00004013840	54457934	54458002
ENSE00004013841	54455967	54456245
ENSE00004013842	54455364	54455567
ENSE00004013843	54458103	54458232
ENSE00004013844	54456636	54456921
ENSE00004013845	54452651	54452752

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.3752 / max 2099.2515, expressed in 1825 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177505	97.6230	1824
177522	3.5418	1211
177523	3.4494	1095
177506	1.9361	1139
177521	1.8282	864
177512	0.6923	395
177515	0.6758	391
177520	0.6174	366
177508	0.5803	312
177504	0.5215	254

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.38	gold quality
pituitary gland	UBERON:0000007	99.36	gold quality
adenohypophysis	UBERON:0002196	99.32	gold quality
cerebellar hemisphere	UBERON:0002245	99.30	gold quality
cerebellar cortex	UBERON:0002129	99.29	gold quality
cerebellum	UBERON:0002037	99.28	gold quality
right lobe of thyroid gland	UBERON:0001119	99.20	gold quality
left lobe of thyroid gland	UBERON:0001120	99.17	gold quality
left ovary	UBERON:0002119	99.17	gold quality
spleen	UBERON:0002106	99.15	gold quality
endocervix	UBERON:0000458	99.13	gold quality
right ovary	UBERON:0002118	99.13	gold quality
body of uterus	UBERON:0009853	99.11	gold quality
body of pancreas	UBERON:0001150	99.10	gold quality
fundus of stomach	UBERON:0001160	99.09	gold quality
left uterine tube	UBERON:0001303	99.09	gold quality
tibial nerve	UBERON:0001323	99.09	gold quality
thyroid gland	UBERON:0002046	99.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.00	gold quality
mucosa of stomach	UBERON:0001199	98.99	gold quality
left testis	UBERON:0004533	98.98	gold quality
right testis	UBERON:0004534	98.94	gold quality
prostate gland	UBERON:0002367	98.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.92	gold quality
lower esophagus mucosa	UBERON:0035834	98.87	gold quality
right coronary artery	UBERON:0001625	98.86	gold quality
small intestine	UBERON:0002108	98.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.85	gold quality
ovary	UBERON:0000992	98.82	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	362.03
E-GEOD-137537	yes	22.29
E-ANND-3	yes	7.67
E-HCAD-30	no	343.39
E-MTAB-4850	no	285.18
E-CURD-7	no	15.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting LENG8, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3925-3P	100.00	69.95	1237
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-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 48.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• genetic polymorphism is associated with pemphigus foliaceus (PMID:30216441)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	leng8	ENSDARG00000076805
mus_musculus	Leng8	ENSMUSG00000035545
rattus_norvegicus	Leng8	ENSRNOG00000018642
caenorhabditis_elegans		WBGENE00017158

Paralogs (2): MCM3AP (ENSG00000160294), SAC3D1 (ENSG00000168061)

Protein

Protein identifiers

Leukocyte receptor cluster member 8 — Q96PV6 (reviewed: Q96PV6)

All UniProt accessions (7): A0A087WUE4, B0VJY8, C9J1N5, C9JMY0, E7EWC7, Q96PV6, H7BZP5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May be part of a SEM1-containing complex.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96PV6-2	1	yes
Q96PV6-1	2
Q96PV6-3	3

RefSeq proteins (6): NP_001362567, NP_001362568, NP_001362569, NP_001362570, NP_001397992, NP_443157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR005062	SAC3/GANP/THP3_conserved	Domain
IPR045107	SAC3/GANP/THP3	Family

Pfam: PF03399

UniProt features (20 total): compositionally biased region 6, splice variant 3, sequence variant 3, region of interest 3, modified residue 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9T6L	ELECTRON MICROSCOPY	2.9
9DLV	ELECTRON MICROSCOPY	2.97
9DLR	ELECTRON MICROSCOPY	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PV6-F1	56.38	0.04

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): 2, 351

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, TGCGCANK_UNKNOWN, MCCLUNG_COCAINE_REWARD_5D, AACTGGA_MIR145, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, YGCGYRCGC_UNKNOWN, AHR_Q5, GARY_CD5_TARGETS_UP, CAGTGTT_MIR141_MIR200A, GINESTIER_BREAST_CANCER_20Q13_AMPLIFICATION_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_UP, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, HES4_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1
cellular_component	1

Protein interactions and networks

STRING

1108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LENG8	CDC42EP5	Q6NZY7	666
LENG8	TTYH1	Q9H313	649
LENG8	LENG9	Q96B70	614
LENG8	LAIR2	Q6ISS4	574
LENG8	LAIR1	Q6GTX8	560
LENG8	FNBP4	Q8N3X1	551
LENG8	FCAR	P24071	524
LENG8	RPS9	P46781	493
LENG8	HACL2	A1L0T0	480
LENG8	VSTM1	Q6UX27	477
LENG8	RPL37	P02403	450
LENG8	OLA1	Q9NTK5	431
LENG8	LILRA5	A6NI73	406
LENG8	NCR1	O76036	398
LENG8	CTPS2	Q9NRF8	398

IntAct

252 interactions, top by confidence:

A	B	Type	Score
SNRPA	LENG8	psi-mi:“MI:0915”(physical association)	0.780
LENG8	SNRPA	psi-mi:“MI:0915”(physical association)	0.780
NCBP3	LENG8	psi-mi:“MI:0915”(physical association)	0.740
LENG8	MAPK1IP1L	psi-mi:“MI:0915”(physical association)	0.700
MAPK1IP1L	LENG8	psi-mi:“MI:0915”(physical association)	0.700
CEP70	LENG8	psi-mi:“MI:0915”(physical association)	0.560
LENG8	COG2	psi-mi:“MI:0915”(physical association)	0.560
	LENG8	psi-mi:“MI:0915”(physical association)	0.560
ATN1	LENG8	psi-mi:“MI:0915”(physical association)	0.560
LENG8	MAGED1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPM	LENG8	psi-mi:“MI:0915”(physical association)	0.560
FAM22F	LENG8	psi-mi:“MI:0915”(physical association)	0.560
TNIP1	LENG8	psi-mi:“MI:0915”(physical association)	0.560
LENG8	TRAF4	psi-mi:“MI:0915”(physical association)	0.560
MIA3	LENG8	psi-mi:“MI:0915”(physical association)	0.560
TLE5	LENG8	psi-mi:“MI:0915”(physical association)	0.560
CPSF7	LENG8	psi-mi:“MI:0915”(physical association)	0.560
BAG3	LENG8	psi-mi:“MI:0915”(physical association)	0.560
LENG8	CAMK2A	psi-mi:“MI:0915”(physical association)	0.560
LENG8	IKBKG	psi-mi:“MI:0915”(physical association)	0.560
TFG	LENG8	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LENG8	psi-mi:“MI:0915”(physical association)	0.560
DVL3	LENG8	psi-mi:“MI:0915”(physical association)	0.560
PER2	LENG8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (188): LENG8 (Two-hybrid), LENG8 (Two-hybrid), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Two-hybrid), LENG8 (Affinity Capture-MS), LENG8 (Two-hybrid), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS), LENG8 (Affinity Capture-MS)

ESM2 similar proteins: A4QNR8, F4IUY8, O14964, O74555, O75061, O88339, O95208, P16371, P49848, P83038, P97496, Q0V8S0, Q27974, Q32NW2, Q5BFH3, Q5SNN4, Q62311, Q63801, Q641G3, Q659C4, Q6GLQ4, Q6NZC7, Q6PGA0, Q6PKG0, Q6Z358, Q6ZQ58, Q80TZ3, Q80VP1, Q8CBY3, Q8CH18, Q8CHU3, Q8INR6, Q8IQ05, Q8L860, Q8TEH3, Q8TFZ1, Q8VDM6, Q91857, Q92783, Q95YE2

Diamond homologs: A4QNR8, Q12049, Q1MTP1, Q32NW2, Q8CBY3, Q96PV6, F4IUY8, Q67XV2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	5	17.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	124
Likely benign	13
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2172 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54452088:T:TA	acceptor_gain	1.0000
19:54452091:A:AG	acceptor_gain	1.0000
19:54452091:AG:A	acceptor_gain	1.0000
19:54452092:G:GT	acceptor_gain	1.0000
19:54452092:GG:G	acceptor_gain	1.0000
19:54452092:GGT:G	acceptor_gain	1.0000
19:54452092:GGTC:G	acceptor_gain	1.0000
19:54452092:GGTCT:G	acceptor_gain	1.0000
19:54452265:CAGG:C	donor_loss	1.0000
19:54452266:AGG:A	donor_loss	1.0000
19:54452268:G:GG	donor_gain	1.0000
19:54452640:T:A	acceptor_gain	1.0000
19:54452648:CA:C	acceptor_loss	1.0000
19:54452649:A:AG	acceptor_gain	1.0000
19:54452649:A:AT	acceptor_loss	1.0000
19:54452649:AGTAC:A	acceptor_gain	1.0000
19:54452650:G:GA	acceptor_gain	1.0000
19:54452650:GT:G	acceptor_gain	1.0000
19:54452650:GTA:G	acceptor_gain	1.0000
19:54452650:GTAC:G	acceptor_gain	1.0000
19:54452650:GTACG:G	acceptor_gain	1.0000
19:54452748:CCATG:C	donor_gain	1.0000
19:54452749:CATG:C	donor_gain	1.0000
19:54452749:CATGG:C	donor_loss	1.0000
19:54452750:ATG:A	donor_gain	1.0000
19:54452750:ATGG:A	donor_loss	1.0000
19:54452751:TG:T	donor_gain	1.0000
19:54452751:TGG:T	donor_loss	1.0000
19:54452752:GG:G	donor_gain	1.0000
19:54452753:G:GA	donor_loss	1.0000

AlphaMissense

5209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54452169:T:A	W39R	1.000
19:54452169:T:C	W39R	1.000
19:54452170:G:C	W39S	1.000
19:54452171:G:C	W39C	1.000
19:54452171:G:T	W39C	1.000
19:54452179:C:A	A42D	1.000
19:54452181:C:A	R43S	1.000
19:54452182:G:C	R43P	1.000
19:54452187:G:C	A45P	1.000
19:54452191:T:C	L46P	1.000
19:54455407:T:A	W289R	1.000
19:54455407:T:C	W289R	1.000
19:54455409:G:C	W289C	1.000
19:54455409:G:T	W289C	1.000
19:54455428:T:A	Y296N	1.000
19:54455428:T:C	Y296H	1.000
19:54455428:T:G	Y296D	1.000
19:54455429:A:C	Y296S	1.000
19:54455429:A:G	Y296C	1.000
19:54455432:T:A	V297E	1.000
19:54455438:G:C	R299P	1.000
19:54455440:T:C	C300R	1.000
19:54455441:G:A	C300Y	1.000
19:54455442:C:G	C300W	1.000
19:54455443:T:C	F301L	1.000
19:54455444:T:C	F301S	1.000
19:54455444:T:G	F301C	1.000
19:54455445:C:A	F301L	1.000
19:54455445:C:G	F301L	1.000
19:54455453:G:A	C304Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000128531 (19:54461898 T>C), RS1000163558 (19:54450666 A>C,G), RS1000304964 (19:54452632 T>A,C,G), RS1000481171 (19:54462022 A>G,T), RS1000642370 (19:54451374 C>G,T), RS1000829280 (19:54460584 AACCCCCCCCGG>A), RS1000999771 (19:54460230 G>C,T), RS1001177169 (19:54460432 C>A), RS1001435258 (19:54454367 C>T), RS1001650799 (19:54448662 G>A,C), RS1001796853 (19:54447360 A>C,G), RS1001854528 (19:54459422 T>A), RS1001926373 (19:54459707 G>A,T), RS1002034974 (19:54455445 C>T), RS1002049654 (19:54447272 G>A)

Disease associations

OMIM: gene MIM:616575 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523745 (PROTEIN-PROTEIN INTERACTION), CHEMBL6067462 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.14	Kd	72	nM	MOLIBRESIB
7.00	IC50	100	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 9 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179235: Binding affinity against LENG8 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0720	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
resorcinol	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
mono(2-ethyl-5-oxohexyl)phthalate	affects expression	1
obeticholic acid	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Atrazine	increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methapyrilene	decreases methylation	1
Polychlorinated Biphenyls	affects expression	1
Quercetin	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4324645	Binding	Protac activity against VHL/LENG8 in human HT-29 cells harboring with BRAF V600E variant assessed as reduction in LENG8 protein level at 0.1 uM after 10 hrs by LC-MS based Volcano plot analysis	Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader. — J Med Chem

Clinical trials (associated diseases)

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