LAPTM4B

Summary

LAPTM4B (lysosomal protein transmembrane 4 beta, HGNC:13646) is a protein-coding gene on chromosome 8q22.1, encoding Lysosomal-associated transmembrane protein 4B (Q86VI4). Required for optimal lysosomal function.

Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including endosome transport via multivesicular body sorting pathway; negative regulation of macromolecule metabolic process; and regulation of lysosomal membrane permeability. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane.

Source: NCBI Gene 55353 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_018407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13646
Approved symbol	LAPTM4B
Name	lysosomal protein transmembrane 4 beta
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	LC27
Ensembl gene	ENSG00000104341
Ensembl biotype	protein_coding
OMIM	613296
Entrez	55353

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000445593, ENST00000517924, ENST00000521545, ENST00000619747, ENST00000883453, ENST00000883454, ENST00000883455, ENST00000929553, ENST00000929554, ENST00000929555, ENST00000929556, ENST00000929557

RefSeq mRNA: 1 — MANE Select: NM_018407 NM_018407

CCDS: CCDS6275

Canonical transcript exons

ENST00000521545 — 7 exons

Exon	Start	End
ENSE00000981125	97805353	97805464
ENSE00000981126	97815328	97815401
ENSE00000981127	97816058	97816180
ENSE00000981128	97819140	97819238
ENSE00000981129	97825058	97825153
ENSE00002091226	97775788	97776108
ENSE00002275242	97851397	97853013

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 103.5735 / max 1792.7470, expressed in 1712 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89901	77.9272	1695
89902	25.6463	1577

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.76	gold quality
choroid plexus epithelium	UBERON:0003911	99.65	gold quality
heart right ventricle	UBERON:0002080	99.64	gold quality
myocardium	UBERON:0002349	99.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.62	gold quality
pancreatic ductal cell	CL:0002079	99.60	gold quality
secondary oocyte	CL:0000655	99.42	gold quality
left ventricle myocardium	UBERON:0006566	99.42	gold quality
type B pancreatic cell	CL:0000169	99.41	gold quality
biceps brachii	UBERON:0001507	99.40	gold quality
germinal epithelium of ovary	UBERON:0001304	99.36	gold quality
epithelial cell of pancreas	CL:0000083	99.35	gold quality
endothelial cell	CL:0000115	99.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.33	gold quality
oocyte	CL:0000023	99.31	gold quality
vastus lateralis	UBERON:0001379	99.25	gold quality
hair follicle	UBERON:0002073	99.22	gold quality
quadriceps femoris	UBERON:0001377	99.15	gold quality
adult organism	UBERON:0007023	99.09	gold quality
triceps brachii	UBERON:0001509	98.85	gold quality
parotid gland	UBERON:0001831	98.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.84	gold quality
renal glomerulus	UBERON:0000074	98.82	gold quality
metanephric glomerulus	UBERON:0004736	98.78	gold quality
deltoid	UBERON:0001476	98.77	gold quality
gingival epithelium	UBERON:0001949	98.73	gold quality
adrenal tissue	UBERON:0018303	98.71	gold quality
cervix squamous epithelium	UBERON:0006922	98.69	gold quality
kidney epithelium	UBERON:0004819	98.65	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	4318.99
E-MTAB-9067	yes	573.62
E-MTAB-10287	yes	48.11
E-CURD-112	yes	37.34
E-HCAD-6	yes	33.81
E-HCAD-10	yes	18.59
E-GEOD-135922	yes	12.70
E-MTAB-7249	yes	11.26
E-MTAB-10283	no	585.07
E-MTAB-7303	no	493.10
E-MTAB-9388	no	9.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

70 targeting LAPTM4B, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-889-5P	99.41	68.75	1025

Literature-anchored findings (GeneRIF, showing 40)

• LAPTM4B gene encoded two isoforms of tetratransmembrane proteins, LAPTM4B-35 and LAPTM4B-24 and expression of LAPTM4B-35 protein is upregulated and associated with poor differentiation in human hepatocellular carcinoma tissues (PMID:15162524)
• LAPTM4b has active role in disease progression of malignant cells and is involved in cell proliferation and multidrug resistance (PMID:15911104)
• We have demonstrated intergenic splicing between two sets of family genes, the matrilin-3 (MATN3) and lysosomal-associated protein transmembrane 4alpha (LAPTM4A). (PMID:16769693)
• LAPTM4B gene polymorphism is associated with gastric cancer (PMID:17074969)
• These results indicate that the genetic polymorphism of LAPTM4B is a potential risk factor for the development of colon cancer. (PMID:17965115)
• LAPTM4B-35 positively expressed in a great portion of extrahepatic cholangiocarcinoma and might be a novel molecular maker of progression, invasiveness and poor prognosis. (PMID:18334282)
• LAPTM4B may be a clinically useful prognostic indicator for ovarian carcinoma. (PMID:18949404)
• LAPTM4B-35 expression showed a strong association with recurrence, metastasis and progression of hepatoma. (PMID:19690886)
• LAPTM4B-35 and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells. (PMID:19843073)
• LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinoma. (PMID:20358632)
• LAPTM4B expressed in GBC-SD cells at a relatively low level. Forced overexpression of LAPTM4B increased invasive potential of GBC-SD cells, through modulating molecules associated with degradation of extracellular matrix. (PMID:20583413)
• LAPTM4B-35 motivates multidrug resistance of cancer cells by promoting drug efflux (PMID:20711237)
• LAPTM4B-35 may be associated with tumor progression in cervical carcinoma (PMID:20881850)
• Over-expression of LAPTM4B is associated with chemotherapy resistance and stages III and IV epithelial ovarian cancer (PMID:21416470)
• overexpression of LAPTM4B-35 attenuated epirubicin-induced apoptosis of gallbladder carcinoma GBC-SD cells through a mitochondria-dependent pathway (PMID:21429547)
• Upregulation of LAPTM4B-35 promotes malignant transformation and liver tumorigenesis. (PMID:21618708)
• the LAPTM4B*2 allele might be a cervical cancer risk factor and may play an important role in genetic susceptibility to cervical cancer in the Chinese population. (PMID:21656743)
• Data show that LAPTM4B protein was localized in lysosomes where its depletion increased membrane permeability, pH, cathepsin release, and cellular apoptosis. (PMID:22037872)
• gene polymorphism of LAPTM4B may influence the individuals’ susceptibility to primary liver cancer. (PMID:22156622)
• LAPTM4B expression was found to have a significant inverse correlation on prognosis in patients with metastatic ovarian tumors and may be an independent prognostic marker for metastatic ovarian tumors. (PMID:22193644)
• allele *2 of LAPTM4B appears to be associated with genetic susceptibility of HCC and may therefore be considered as a risk factor. (PMID:22207410)
• LAPTM4B allelic variation was significantly associated with breast cancer occurrence, with adjusted odds ratios of 1.387 (95%CI = 1.111-1.730) for LAPTM4B*1/2 and 1.592 (95% CI = 1.043-2.430) for LAPTM4B*2/2 genotype. (PMID:22270081)
• LAPTM4B allele *2 may be a risk factor associated with genetic susceptibility to GBC. (PMID:22302286)
• Findings indicate that the LAPTM4B 2 allele may be a risk factor for ovarian cancer and may play an important role in genetic susceptibility to ovarian cancer. (PMID:22412199)
• LAPTM4B is a risk factor associated with poor prognosis in patients with resected HCC. LAPTM4B status may be useful preoperatively as an adjunct in evaluation of the operability of HCC. (PMID:22509374)
• LAPTM4B overexpression is an independent factor in poor colorectal cancer prognosis, and it may be an important potential biomarker. (PMID:22578410)
• LAPTM4B-35 was found to be present at high levels in a large proportion of patients with pancreatic carcinoma, and was closely related to disease progression and poor prognosis. (PMID:22971479)
• LAPTM4B*2 is a risk factor associated with breast cancer susceptibility and poor prognosis (PMID:22984585)
• Data suggest that lysosomal protein transmembrane 4 beta (LAPTM4B) status may be useful in preoperative evaluation of the operability of gallbladder carcinoma (GBC). (PMID:22984631)
• LAPTM4B was found to not exhibit any expression changes between different classes of pituitary adenomas. (PMID:23023342)
• High LAPTM4B expression is associated with lymph node metastasis, and recurrence in breast cancer. (PMID:23292099)
• Endometrial carcinoma patients with LAPTM4B *2 variant had both significantly shorter overall survival and disease-free survival. (PMID:23312008)
• The results of our study indicated that the polymorphism of LAPTM4B gene did not influence the susceptibility of nasopharyngeal carcinoma in the Chinese population (PMID:23345117)
• SNPs in lysosomal-associated transmembrane protein 4 beta (LAPTM4B) and insulin-like growth factor 1 (IGF1) were associated with both susceptibility to and curve severity in adolescent idiopathic scoliosis in Korea. (PMID:23364988)
• study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells (PMID:23469012)
• LAPTM4B, with increased expression in airways at shorter distance from tumors, was upregulated in human immortalized cells compared with normal bronchial epithelial cells and promoted anchorage-dependent and independent lung cancer cell growth. (PMID:24563515)
• Overexpression of LAPTM4B-35 may be associated with tumor progression and poor prognosis in prostate cancer. (PMID:24651764)
• The results suggest that LAPTM4B polymorphisms may be a prospective marker for evaluating the risk and prognosis of non-small cell lung cancer. (PMID:24676601)
• The LAPTM4B *2 allele was associated with increasing risk of multiple cancers, tumor initiation and development in Chinese populations. [meta-analysis] (PMID:24746178)
• Overexpression of LAPTM4B protein is correlated with tumor angiogenesis and poor prognosis in non-small cell lung cancer. (PMID:24816841)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	laptm4b	ENSDARG00000035870
mus_musculus	Laptm4b	ENSMUSG00000022257
rattus_norvegicus	Laptm4b	ENSRNOG00000006766
drosophila_melanogaster	CG14767	FBGN0040777

Paralogs (2): LAPTM4A (ENSG00000068697), LAPTM5 (ENSG00000162511)

Protein

Protein identifiers

Lysosomal-associated transmembrane protein 4B — Q86VI4 (reviewed: Q86VI4)

Alternative names: Lysosome-associated transmembrane protein 4-beta

All UniProt accessions (2): Q86VI4, H0YBN1

UniProt curated annotations — full annotation on UniProt →

Function. Required for optimal lysosomal function. Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation. Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation. Plays a role as negative regulator of TGFB1 production in regulatory T cells. Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways.

Subunit / interactions. Homooligomer; upon reaching the lysosomes. Interacts with MCOLN1. Interacts with NEDD4; may play a role in the lysosomal sorting of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of EGFR degradation. Interacts with PIP5K1C; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C. Interacts with HGS; promotes HGS ubiquitination. Interacts with SNX5. Interacts with SLC3A2 and SLC7A5; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation. Interacts with LRRC32; decreases TGFB1 production in regulatory T cells. Interacts with BECN1; competes with EGFR for LAPTM4B binding; regulates EGFR activity. Interacts with EGFR; positively correlates with EGFR activation.

Subcellular location. Endomembrane system. Late endosome membrane. Cell membrane. Cell projection. Lysosome membrane. Endosome membrane. Endosome. Multivesicular body membrane. Multivesicular body lumen.

Post-translational modifications. Undergoes proteolytic cleavage following delivery to the lysosomes. Ubiquitinated by NEDD4.

Similarity. Belongs to the LAPTM4/LAPTM5 transporter family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86VI4-3	1	yes
Q86VI4-2	2

RefSeq proteins (1): NP_060877* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004687	LAPTM4/5	Family
IPR051115	LAPTM_transporter	Family

Pfam: PF03821

UniProt features (14 total): transmembrane region 4, sequence conflict 3, mutagenesis site 2, region of interest 2, chain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VI4-F1	64.48	0.06

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
312	abolishes binding to nedd4; when associated with a-296. increases localization to cell membrane; when associated with a-
296	abolishes binding to nedd4; when associated with a-312. increases localization to cell membrane; when associated with a-

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): VALK_AML_WITH_FLT3_ITD, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_ENDOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, MATTIOLI_MGUS_VS_PCL, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KEGG_LYSOSOME, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, PRAMOONJAGO_SOX4_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, KOINUMA_COLON_CANCER_MSI_DN

GO Biological Process (6): endosome organization (GO:0007032), endosome transport via multivesicular body sorting pathway (GO:0032509), negative regulation of transforming growth factor beta1 production (GO:0032911), regulation of lysosomal membrane permeability (GO:0097213), negative regulation of lysosomal protein catabolic process (GO:1905166), regulation of lysosome organization (GO:1905671)

GO Molecular Function (5): kinase binding (GO:0019900), ubiquitin protein ligase binding (GO:0031625), ceramide binding (GO:0097001), phosphatidylinositol bisphosphate binding (GO:1902936), protein binding (GO:0005515)

GO Cellular Component (12): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), early endosome (GO:0005769), plasma membrane (GO:0005886), late endosome membrane (GO:0031902), multivesicular body membrane (GO:0032585), cell projection (GO:0042995), multivesicular body, internal vesicle (GO:0097487), endosome membrane (GO:0010008), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endosome	2
multivesicular body	2
endomembrane system organization	1
vesicle organization	1
endosomal transport	1
multivesicular body sorting pathway	1
transforming growth factor beta1 production	1
regulation of transforming growth factor beta1 production	1
negative regulation of transforming growth factor beta production	1
regulation of membrane permeability	1
negative regulation of protein catabolic process in the vacuole	1
lysosomal protein catabolic process	1
regulation of lysosomal protein catabolic process	1
lysosome organization	1
regulation of vacuole organization	1
enzyme binding	1
ubiquitin-like protein ligase binding	1
sphingolipid binding	1
anion binding	1
binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
late endosome	1
endosome membrane	1
late endosome membrane	1
endosomal intralumenal vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAPTM4B	EGFR	P00533	898
LAPTM4B	YWHAZ	P29213	677
LAPTM4B	EXOC2	Q96KP1	649
LAPTM4B	BECN1	Q14457	621
LAPTM4B	AANAT	Q16613	580
LAPTM4B	SMIM24	O75264	571
LAPTM4B	NYNRIN	Q9P2P1	523
LAPTM4B	CPXM1	Q96SM3	518
LAPTM4B	C1orf141	Q5JVX7	464
LAPTM4B	BEX3	Q00994	459
LAPTM4B	SLC7A5	Q01650	450
LAPTM4B	ARHGAP22	Q7Z5H3	445
LAPTM4B	RIN1	Q13671	440
LAPTM4B	PLAAT2	Q9NWW9	433
LAPTM4B	SLC3A2	P08195	419

IntAct

103 interactions, top by confidence:

A	B	Type	Score
EGFR	LAPTM4B	psi-mi:“MI:0403”(colocalization)	0.600
LAPTM4B	EGFR	psi-mi:“MI:0915”(physical association)	0.600
EGFR	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.600
NAALADL2	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
CYB561A3	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
SCARB2	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4B	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
IFNAR1	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
CTXN3	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
NRG1	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
GJA8	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
ODF4	LAPTM4B	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4B	GPX8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (65): NAALADL2 (Two-hybrid), LAPTM4B (Affinity Capture-Western), PIP5K1C (Affinity Capture-Western), PIP5K1C (Reconstituted Complex), HGS (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), LAPTM4B (Affinity Capture-Western), SNX5 (Affinity Capture-Western), LAPTM4B (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS)

ESM2 similar proteins: A2A690, A2A7Q9, A2RRU4, A6QM06, D3ZEH5, D4A6L0, E1BBQ2, E9Q6C8, F1LTE0, O42224, O46606, P56726, P97260, P97698, Q08BT5, Q0PMD2, Q12770, Q13563, Q3TDN0, Q5GH57, Q5GH73, Q5MNU5, Q5RH73, Q5T6S3, Q5T848, Q5U239, Q5ZII3, Q68FF6, Q68FW3, Q6DFZ1, Q6GQT6, Q6ZMZ0, Q6ZN54, Q791F6, Q86VI4, Q86W33, Q8C419, Q8C4U2, Q8CIF6, Q8K4P7

Diamond homologs: C4QM85, Q15012, Q4R4I5, Q4R6E8, Q5DC12, Q5RAH0, Q5U1W4, Q5ZML7, Q60961, Q6P501, Q6QRN8, Q71SV0, Q86VI4, Q91XQ6, Q5J7P3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
Constitutive Signaling by Aberrant PI3K in Cancer	7	21.1×	9e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	16.1×	3e-05
PIP3 activates AKT signaling	7	11.1×	2e-04
RAF/MAP kinase cascade	7	10.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1617 predictions. Top by Δscore:

Variant	Effect	Δscore
8:97793581:A:T	donor_gain	1.0000
8:97805347:TTGCA:T	acceptor_loss	1.0000
8:97805348:TGCAG:T	acceptor_loss	1.0000
8:97805349:GCAGA:G	acceptor_loss	1.0000
8:97805350:CAGA:C	acceptor_loss	1.0000
8:97805351:A:AG	acceptor_gain	1.0000
8:97805351:A:AT	acceptor_loss	1.0000
8:97805352:G:GA	acceptor_gain	1.0000
8:97805352:GATC:G	acceptor_gain	1.0000
8:97805460:TGCCA:T	donor_gain	1.0000
8:97805461:GCCA:G	donor_gain	1.0000
8:97805461:GCCAG:G	donor_gain	1.0000
8:97805462:CCA:C	donor_gain	1.0000
8:97805463:CA:C	donor_gain	1.0000
8:97805464:AGTAA:A	donor_loss	1.0000
8:97805465:G:GG	donor_gain	1.0000
8:97805465:GTAA:G	donor_loss	1.0000
8:97805466:TAA:T	donor_loss	1.0000
8:97805469:GTA:G	donor_gain	1.0000
8:97815322:C:CA	acceptor_gain	1.0000
8:97815327:GAC:G	acceptor_gain	1.0000
8:97815327:GACAT:G	acceptor_gain	1.0000
8:97815400:AGG:A	donor_loss	1.0000
8:97815402:G:T	donor_loss	1.0000
8:97816054:TTA:T	acceptor_loss	1.0000
8:97816056:A:AG	acceptor_gain	1.0000
8:97816056:A:C	acceptor_loss	1.0000
8:97816057:G:GT	acceptor_gain	1.0000
8:97816057:GC:G	acceptor_gain	1.0000
8:97816057:GCA:G	acceptor_gain	1.0000

AlphaMissense

1485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:97819218:A:C	S254R	0.994
8:97819220:C:A	S254R	0.994
8:97819220:C:G	S254R	0.994
8:97776094:G:C	G120R	0.992
8:97816080:C:A	P194Q	0.992
8:97816082:T:C	F195L	0.991
8:97816084:C:A	F195L	0.991
8:97816084:C:G	F195L	0.991
8:97776095:G:A	G120D	0.990
8:97816080:C:G	P194R	0.990
8:97819238:G:C	K260N	0.990
8:97819238:G:T	K260N	0.990
8:97776100:T:A	W122R	0.989
8:97776100:T:C	W122R	0.989
8:97816088:T:C	C197R	0.988
8:97825079:T:A	W268R	0.988
8:97825079:T:C	W268R	0.988
8:97776080:G:A	G115D	0.987
8:97815391:G:A	G183E	0.987
8:97776071:T:A	V112D	0.986
8:97815370:T:A	I176K	0.986
8:97776107:T:C	L124P	0.985
8:97805361:T:A	N127K	0.985
8:97805361:T:G	N127K	0.985
8:97815390:G:A	G183R	0.984
8:97815390:G:C	G183R	0.984
8:97776079:G:C	G115R	0.981
8:97825085:T:C	C270R	0.981
8:97815372:T:C	C177R	0.980
8:97815382:C:A	A180D	0.980

dbSNP variants (sampled 300 via entrez): RS1000044533 (8:97788474 C>T), RS1000056402 (8:97776407 C>G,T), RS1000059421 (8:97789579 G>A), RS1000061901 (8:97804325 A>G), RS1000118760 (8:97813220 C>T), RS1000128328 (8:97776551 G>A), RS1000132758 (8:97811174 G>A), RS1000175565 (8:97807390 G>T), RS1000243181 (8:97804715 A>C,T), RS1000249196 (8:97807765 A>G), RS1000330044 (8:97781924 A>G), RS1000396323 (8:97839255 C>T), RS1000405106 (8:97802307 A>G), RS1000447308 (8:97839413 G>A,C), RS1000461779 (8:97778038 CCAGA>C)

Disease associations

OMIM: gene MIM:613296 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002500_64	QT interval	2.000000e-10
GCST009391_2132	Metabolite levels	7.000000e-06
GCST009391_441	Metabolite levels	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0010383	phosphatidylcholine 36:5 measurement
EFO:0010385	phosphatidylcholine 38:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, increases expression, affects response to substance	3
Tretinoin	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases abundance	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Copper	affects binding, decreases expression	1
Doxorubicin	affects expression	1
Phenobarbital	affects expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0GA	Ubigene HeLa LAPTM4B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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