LAPTM4A

Summary

LAPTM4A (lysosomal protein transmembrane 4 alpha, HGNC:6924) is a protein-coding gene on chromosome 2p24.1, encoding Lysosomal-associated transmembrane protein 4A (Q15012). May function in the transport of nucleosides and/or nucleoside derivatives between the cytosol and the lumen of an intracellular membrane-bound compartment.

This gene encodes a protein that has four predicted transmembrane domains. The function of this gene has not yet been determined; however, studies in the mouse homolog suggest a role in the transport of small molecules across endosomal and lysosomal membranes.

Source: NCBI Gene 9741 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_014713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6924
Approved symbol	LAPTM4A
Name	lysosomal protein transmembrane 4 alpha
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	HUMORF13, KIAA0108, Mtrp, LAPTM4
Ensembl gene	ENSG00000068697
Ensembl biotype	protein_coding
OMIM	618837
Entrez	9741

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000175091, ENST00000483117, ENST00000858090, ENST00000858091, ENST00000858092, ENST00000911489, ENST00000911490, ENST00000941941

RefSeq mRNA: 1 — MANE Select: NM_014713 NM_014713

CCDS: CCDS1696

Canonical transcript exons

ENST00000175091 — 7 exons

Exon	Start	End
ENSE00000901179	20032650	20033279
ENSE00000901181	20034967	20035062
ENSE00000901182	20037316	20037438
ENSE00000901183	20037538	20037614
ENSE00000901184	20040891	20041011
ENSE00001070920	20051410	20051628
ENSE00003670648	20034317	20034415

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 166.3038 / max 878.3755, expressed in 1821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27082	69.6476	1813
27083	53.4693	1817
27081	42.4381	1789
27085	0.5400	203
27080	0.1838	87
27084	0.0249	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.89	gold quality
adult organism	UBERON:0007023	99.76	gold quality
germinal epithelium of ovary	UBERON:0001304	99.73	gold quality
skin of hip	UBERON:0001554	99.73	gold quality
synovial joint	UBERON:0002217	99.71	gold quality
urethra	UBERON:0000057	99.68	gold quality
choroid plexus epithelium	UBERON:0003911	99.67	gold quality
caput epididymis	UBERON:0004358	99.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.67	gold quality
cauda epididymis	UBERON:0004360	99.65	gold quality
superficial temporal artery	UBERON:0001614	99.64	gold quality
endometrium	UBERON:0001295	99.63	gold quality
corpus epididymis	UBERON:0004359	99.62	gold quality
right testis	UBERON:0004534	99.62	gold quality
tibia	UBERON:0000979	99.61	gold quality
penis	UBERON:0000989	99.61	gold quality
mammalian vulva	UBERON:0000997	99.61	gold quality
stromal cell of endometrium	CL:0002255	99.60	gold quality
upper leg skin	UBERON:0004262	99.59	gold quality
blood vessel layer	UBERON:0004797	99.59	gold quality
renal medulla	UBERON:0000362	99.58	gold quality
trigeminal ganglion	UBERON:0001675	99.58	gold quality
left testis	UBERON:0004533	99.58	gold quality
bronchial epithelial cell	CL:0002328	99.56	gold quality
mammary duct	UBERON:0001765	99.56	gold quality
uterus	UBERON:0000995	99.55	gold quality
pericardium	UBERON:0002407	99.55	gold quality
endocervix	UBERON:0000458	99.53	gold quality
mammary gland	UBERON:0001911	99.53	gold quality
gall bladder	UBERON:0002110	99.53	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	1972.22
E-MTAB-10042	yes	1360.48
E-HCAD-1	yes	90.60
E-MTAB-8410	yes	70.54
E-HCAD-4	yes	62.20
E-MTAB-6701	yes	52.75
E-MTAB-10287	yes	52.15
E-CURD-88	yes	47.84
E-HCAD-11	yes	44.79
E-HCAD-10	yes	32.96
E-GEOD-134144	yes	32.27
E-GEOD-137537	yes	30.87
E-CURD-46	yes	27.32
E-MTAB-7316	yes	26.70
E-HCAD-5	yes	22.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting LAPTM4A, 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-3613-3P	100.00	76.36	7965
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-340-5P	100.00	72.50	4437
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-320A-3P	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 4)

• hOCT2 interacts with LAPTM4A in lysosomes and late endosomes and regulates endocytotic recruitment. (PMID:21553234)
• LAPTM4alpha is targeted from the Golgi to late endosomes/lysosomes in a manner dependent on the E3 ubiquitin ligase Nedd4-1 and ESCRT proteins. (PMID:33836347)
• New Transcriptomic Biomarkers of 5-Fluorouracil Resistance. (PMID:36675023)
• The role of hsa_circ_0042260/miR-4782-3p/LAPTM4A axis in gestational diabetes mellitus. (PMID:38588560)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	laptm4a	ENSDARG00000006397
mus_musculus	Laptm4a	ENSMUSG00000020585
rattus_norvegicus	Laptm4a	ENSRNOG00000006865
drosophila_melanogaster	CG14767	FBGN0040777

Paralogs (2): LAPTM4B (ENSG00000104341), LAPTM5 (ENSG00000162511)

Protein

Protein identifiers

Lysosomal-associated transmembrane protein 4A — Q15012 (reviewed: Q15012)

Alternative names: Golgi 4-transmembrane-spanning transporter MTP

All UniProt accessions (2): Q15012, Q6IBP4

UniProt curated annotations — full annotation on UniProt →

Function. May function in the transport of nucleosides and/or nucleoside derivatives between the cytosol and the lumen of an intracellular membrane-bound compartment.

Subcellular location. Endomembrane system.

Domain organisation. The C-terminal domain is necessary for retention within intracellular membranes.

Similarity. Belongs to the LAPTM4/LAPTM5 transporter family.

RefSeq proteins (1): NP_055528* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004687	LAPTM4/5	Family
IPR018396	LAPTM_4A/5	Family
IPR051115	LAPTM_transporter	Family

Pfam: PF03821

UniProt features (6 total): transmembrane region 4, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15012-F1	72.37	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.

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 232 (showing top): GOBP_VACUOLE_ORGANIZATION, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_VACUOLAR_MEMBRANE, TGCACTT_MIR519C_MIR519B_MIR519A, KEGG_LYSOSOME, MARTINEZ_RB1_TARGETS_UP, IRF7_01, IGLESIAS_E2F_TARGETS_UP, GOBP_LYTIC_VACUOLE_ORGANIZATION, WHN_B, HAND1E47_01, GOBP_MEMBRANE_ORGANIZATION, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_REGULATION_OF_MEMBRANE_PERMEABILITY, MARTINEZ_RB1_AND_TP53_TARGETS_UP

GO Biological Process (0):

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

GO Cellular Component (5): lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), late endosome membrane (GO:0031902), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
late endosome	1
endosome membrane	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAPTM4A	TM9SF2	Q99805	661
LAPTM4A	SPTSSA	Q969W0	501
LAPTM4A	A4GALT	Q9NPC4	468
LAPTM4A	SIRAL2	Q9NWS6	466
LAPTM4A	B4GALT5	O43286	444
LAPTM4A	TMEM165	Q9HC07	433
LAPTM4A	SAP30BP	Q9UHR5	430
LAPTM4A	YWHAZ	P29213	429
LAPTM4A	EXOC2	Q96KP1	428
LAPTM4A	RAPGEFL1	Q9UHV5	402
LAPTM4A	NAPG	Q99747	397
LAPTM4A	RNFT2	Q96EX2	393
LAPTM4A	HVCN1	Q96D96	391
LAPTM4A	UNC50	Q53HI1	387
LAPTM4A	TAC1	P20366	380

IntAct

64 interactions, top by confidence:

A	B	Type	Score
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
LAPTM4A	TMED8	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	LAPTM4A	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4A	DMWD	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4A	EEF1D	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4A		psi-mi:“MI:0915”(physical association)	0.560
LAPTM4A	UQCRB	psi-mi:“MI:0915”(physical association)	0.560
BRK1	LAPTM4A	psi-mi:“MI:0915”(physical association)	0.560
BAG6	LAPTM4A	psi-mi:“MI:0915”(physical association)	0.560
KLF11	LAPTM4A	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4A	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530

BioGRID (49): LAPTM4A (Affinity Capture-RNA), LAPTM4A (Affinity Capture-MS), LAPTM4A (Affinity Capture-MS), LAPTM4A (Affinity Capture-MS), LAPTM4A (Two-hybrid), LAPTM4A (PCA), LAPTM4A (Affinity Capture-MS), TMED8 (Two-hybrid), FFAR2 (Two-hybrid), LAPTM4A (Two-hybrid), LAPTM4A (Affinity Capture-MS), LAPTM4A (Affinity Capture-MS), LAPTM4A (Proximity Label-MS), LAPTM4A (PCA), LAPTM4A (PCA)

ESM2 similar proteins: A0A1B0GVZ9, A4IFN5, A5PK40, A6NH52, A6NI61, B2LYG4, B2RZC9, B6ID01, D2HKB0, D3ZG27, P86229, Q0VDI3, Q15012, Q15546, Q17QJ2, Q1RLT2, Q2TA01, Q4R4I5, Q4R6E8, Q5H8A4, Q5R7Q1, Q5RAH0, Q5RL79, Q5U3C3, Q5VTY9, Q5ZML7, Q64232, Q6PHN7, Q6QRN8, Q719N3, Q71SV0, Q8BWB6, Q8IY49, Q8N6M3, Q8NFT2, Q8R189, Q8VD53, Q8VDI9, Q8VDR5, Q9CQC4

Diamond homologs: C4QM85, Q15012, Q4R4I5, Q5DC12, Q5J7P3, Q5RAH0, Q5ZML7, Q60961, Q6P501, Q6QRN8, Q9BLM6, Q4R6E8, Q5U1W4, Q71SV0, Q86VI4, Q91XQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1062 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20033276:CGTA:C	acceptor_gain	1.0000
2:20033277:GTA:G	acceptor_gain	1.0000
2:20033278:TA:T	acceptor_gain	1.0000
2:20033280:C:CC	acceptor_gain	1.0000
2:20034411:TAAGC:T	acceptor_gain	1.0000
2:20034412:AAGCC:A	acceptor_loss	1.0000
2:20034413:AGC:A	acceptor_gain	1.0000
2:20034413:AGCCT:A	acceptor_loss	1.0000
2:20034414:GC:G	acceptor_gain	1.0000
2:20034414:GCC:G	acceptor_loss	1.0000
2:20034415:CC:C	acceptor_gain	1.0000
2:20034416:C:CC	acceptor_gain	1.0000
2:20034416:CTGGA:C	acceptor_loss	1.0000
2:20034417:T:G	acceptor_loss	1.0000
2:20034962:CGTA:C	donor_loss	1.0000
2:20034963:GTACC:G	donor_loss	1.0000
2:20034964:TA:T	donor_loss	1.0000
2:20034965:A:C	donor_loss	1.0000
2:20034966:C:G	donor_loss	1.0000
2:20035058:TCAGG:T	acceptor_gain	1.0000
2:20035059:CAGG:C	acceptor_gain	1.0000
2:20035059:CAGGC:C	acceptor_gain	1.0000
2:20035060:AGG:A	acceptor_gain	1.0000
2:20035063:C:CC	acceptor_gain	1.0000
2:20035066:T:TC	acceptor_gain	1.0000
2:20035973:C:CA	donor_gain	1.0000
2:20035974:C:A	donor_gain	1.0000
2:20037307:CACA:C	donor_gain	1.0000
2:20037310:A:AC	donor_gain	1.0000
2:20037311:C:CC	donor_gain	1.0000

AlphaMissense

1531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:20037565:A:C	S94R	0.999
2:20037565:A:T	S94R	0.999
2:20037567:T:G	S94R	0.999
2:20051423:C:T	G33E	0.999
2:20051424:C:A	G33W	0.999
2:20051424:C:G	G33R	0.999
2:20051424:C:T	G33R	0.999
2:20037378:A:G	C124R	0.997
2:20037548:C:T	G100E	0.997
2:20051438:C:T	G28E	0.997
2:20051439:C:G	G28R	0.997
2:20051439:C:T	G28R	0.997
2:20034386:G:C	C186W	0.996
2:20034388:A:G	C186R	0.996
2:20051447:A:T	V25D	0.996
2:20037361:A:C	S129R	0.995
2:20037361:A:T	S129R	0.995
2:20037363:T:G	S129R	0.995
2:20037408:A:G	C114R	0.995
2:20037416:G:T	P111Q	0.995
2:20051435:G:T	T29K	0.995
2:20037549:C:G	G100R	0.994
2:20037549:C:T	G100R	0.994
2:20051423:C:A	G33V	0.994
2:20034394:A:G	W184R	0.993
2:20034394:A:T	W184R	0.993
2:20037416:G:C	P111R	0.993
2:20051445:G:T	R26S	0.993
2:20037422:A:G	L109P	0.992
2:20037554:A:T	V98D	0.992

dbSNP variants (sampled 300 via entrez): RS1000092896 (2:20045033 C>T), RS1000134458 (2:20041685 C>G,T), RS1000322328 (2:20040961 T>A,C), RS1000438543 (2:20041373 A>G), RS1000464855 (2:20032911 T>C), RS1000467676 (2:20039961 G>A), RS1000514318 (2:20037296 T>A), RS1000579254 (2:20033418 T>C), RS1000598680 (2:20047061 C>G), RS1000686235 (2:20050273 T>G), RS1000738849 (2:20047947 G>A,C), RS1000770054 (2:20039710 T>C), RS1000799568 (2:20043784 GAAGT>G), RS1001151497 (2:20051749 G>A,C,T), RS1001238376 (2:20040478 C>A)

Disease associations

OMIM: gene MIM:618837 | 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
GCST001083_3	Major depressive disorder	2.000000e-06
GCST008478_4	Neurological blood protein biomarker levels	3.000000e-22

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, affects methylation	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
nivalenol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Potassium Dichromate	increases expression	1
Thiram	increases expression	1
Valproic Acid	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3A1	Abcam HEK293T LAPTM4A KO	Transformed cell line	Female
CVCL_E0G9	Ubigene HeLa LAPTM4A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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