PSAPL1

Summary

PSAPL1 (prosaposin like 1, HGNC:33131) is a protein-coding gene on chromosome 4p16.1, encoding Proactivator polypeptide-like 1 (Q6NUJ1). May activate the lysosomal degradation of sphingolipids.

This gene encodes a protein that is related to the glycoprotein prosaposin. Based on sequence similarity between the encoded protein and prosaposin, it is predicted that the encoded protein is a preproprotein that is proteolytically processed to generate multiple protein products. These predicted products include saposins A-like, B-like, C-like, and D-like, which may play a role in the lysosomal degradation of sphingolipids.

Source: NCBI Gene 768239 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 135 total
• MANE Select transcript: NM_001085382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33131
Approved symbol	PSAPL1
Name	prosaposin like 1
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178597
Ensembl biotype	protein_coding
Entrez	768239

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000319098

RefSeq mRNA: 1 — MANE Select: NM_001085382 NM_001085382

CCDS: CCDS47009

Canonical transcript exons

ENST00000319098 — 1 exons

Exon	Start	End
ENSE00001279006	7430285	7434930

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 96.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2817 / max 61.8603, expressed in 79 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51282	0.2115	57
51283	0.0543	25
51284	0.0160	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	96.25	gold quality
skin of leg	UBERON:0001511	93.79	gold quality
zone of skin	UBERON:0000014	93.06	gold quality
skin of abdomen	UBERON:0001416	92.98	gold quality
mammalian vulva	UBERON:0000997	91.18	gold quality
nipple	UBERON:0002030	84.60	gold quality
skin of hip	UBERON:0001554	84.46	gold quality
germinal epithelium of ovary	UBERON:0001304	82.26	silver quality
penis	UBERON:0000989	76.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	72.22	gold quality
lower lobe of lung	UBERON:0008949	71.91	gold quality
epithelium of nasopharynx	UBERON:0001951	71.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.88	gold quality
body of stomach	UBERON:0001161	70.14	gold quality
biceps brachii	UBERON:0001507	69.57	gold quality
buccal mucosa cell	CL:0002336	69.40	gold quality
stomach	UBERON:0000945	67.93	gold quality
gingival epithelium	UBERON:0001949	67.44	gold quality
subthalamic nucleus	UBERON:0001906	67.29	gold quality
lateral globus pallidus	UBERON:0002476	67.09	gold quality
trabecular bone tissue	UBERON:0002483	66.40	gold quality
substantia nigra pars reticulata	UBERON:0001966	66.29	gold quality
dorsal plus ventral thalamus	UBERON:0001897	66.23	gold quality
substantia nigra pars compacta	UBERON:0001965	66.10	gold quality
cardia of stomach	UBERON:0001162	66.01	gold quality
saphenous vein	UBERON:0007318	65.96	gold quality
vena cava	UBERON:0004087	65.85	gold quality
cerebellar vermis	UBERON:0004720	65.59	gold quality
medulla oblongata	UBERON:0001896	65.56	gold quality
gingiva	UBERON:0001828	65.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting PSAPL1, 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-574-5P	100.00	66.01	989
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-12131	99.48	68.72	1673

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sftpbb	ENSDARG00000067566
danio_rerio	sftpba	ENSDARG00000094708
mus_musculus	Psapl1	ENSMUSG00000043430
rattus_norvegicus	Psapl1	ENSRNOG00000006845
drosophila_melanogaster	Sap-r	FBGN0000416
caenorhabditis_elegans		WBGENE00004995

Paralogs (2): SFTPB (ENSG00000168878), PSAP (ENSG00000197746)

Protein

Protein identifiers

Proactivator polypeptide-like 1 — Q6NUJ1 (reviewed: Q6NUJ1)

All UniProt accessions (1): Q6NUJ1

UniProt curated annotations — full annotation on UniProt →

Function. May activate the lysosomal degradation of sphingolipids.

Subcellular location. Secreted.

RefSeq proteins (1): NP_001078851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003119	SAP_A	Domain
IPR007856	SapB_1	Domain
IPR008138	SapB_2	Domain
IPR008139	SaposinB_dom	Domain
IPR008373	Saposin	Family
IPR011001	Saposin-like	Homologous_superfamily
IPR021165	Saposin_chordata	Family
IPR051428	Sphingo_Act-Surfact_Prot	Family

Pfam: PF02199, PF03489, PF05184

UniProt features (36 total): disulfide bond 12, domain 6, propeptide 5, chain 5, sequence variant 5, glycosylation site 2, signal peptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUJ1-F1	72.77	0.18

Functional residue map

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

Disulfide bonds (12): 64–140, 67–134, 95–107, 184–254, 187–248, 213–224, 294–366, 297–360, 325–336, 396–469, 399–463, 427–438

Glycosylation sites (2): 201, 311

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH, KEGG_LYSOSOME, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_ORGAN_GROWTH, chr4p16, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ADENYLATE_CYCLASE_INHIBITING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_UROGENITAL_SYSTEM_DEVELOPMENT

GO Biological Process (6): sphingolipid metabolic process (GO:0006665), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), regulation of lipid metabolic process (GO:0019216), prostate gland growth (GO:0060736), epithelial cell differentiation involved in prostate gland development (GO:0060742), lipid metabolic process (GO:0006629)

GO Molecular Function (0):

GO Cellular Component (6): obsolete extracellular space (GO:0005615), lysosome (GO:0005764), cytosol (GO:0005829), membrane (GO:0016020), extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
lipid metabolic process	2
developmental process involved in reproduction	2
prostate gland development	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
regulation of primary metabolic process	1
organ growth	1
epithelial cell differentiation	1
primary metabolic process	1
lytic vacuole	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSAPL1	CNPY1	Q3B7I2	893
PSAPL1	GNLY	P09325	888
PSAPL1	CNPY2	Q9Y2B0	859
PSAPL1	MANF	P55145	718
PSAPL1	CDNF	Q49AH0	690
PSAPL1	MYLIP	Q8WY64	674
PSAPL1	ACVR2A	P27037	549
PSAPL1	MYL11	Q96A32	544
PSAPL1	MYL12B	O14950	491
PSAPL1	AOAH	P28039	463
PSAPL1	PLAU	P00749	440
PSAPL1	AFAP1	Q8N556	436
PSAPL1	SMPD1	P17405	419
PSAPL1	ACIN1	Q9UKV3	397
PSAPL1	FGFR1	P11362	390

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
ZNF550	A2ML1	psi-mi:“MI:0914”(association)	0.350
IFNA4	CTSV	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): PSAPL1 (Affinity Capture-MS), PSAPL1 (Affinity Capture-MS), PSAPL1 (Affinity Capture-MS), PSAPL1 (Affinity Capture-MS)

ESM2 similar proteins: F1R520, O13035, O18823, O35298, O70367, O75829, O77770, O94985, P02771, P02774, P04276, P05067, P07602, P08592, P0C5H9, P0C5I0, P10960, P12023, P17129, P17404, P20097, P21614, P26779, P28039, P28050, P49066, P53601, P53789, P55145, P79307, P80513, P81405, Q02391, Q28789, Q3SZ57, Q49AH0, Q5IS80, Q60495, Q61207, Q61543

Diamond homologs: O13035, P07602, P07988, P10960, P20097, P26779, P81405, Q61207, Q6NUJ1, Q8C1C1, O65390, P40782, P42210, O04057, P42211, Q42456, Q8VYL3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	124
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

69 predictions. Top by Δscore:

Variant	Effect	Δscore
4:7431080:G:GG	donor_gain	0.6900
4:7432670:G:GT	acceptor_gain	0.6000
4:7432671:T:TT	acceptor_gain	0.6000
4:7430893:G:GA	donor_gain	0.5900
4:7431072:GCGGA:G	donor_gain	0.5600
4:7431079:A:AG	donor_gain	0.5500
4:7434159:GCCTC:G	acceptor_gain	0.5500
4:7432647:G:C	acceptor_gain	0.5300
4:7432647:G:GC	acceptor_gain	0.5300
4:7434273:TC:T	donor_gain	0.5200
4:7434158:AGCCT:A	acceptor_gain	0.5000
4:7431075:GA:G	donor_gain	0.4900
4:7431037:C:G	donor_gain	0.4500
4:7431076:A:G	donor_gain	0.4400
4:7433142:CGT:C	acceptor_gain	0.4400
4:7431078:GA:G	donor_gain	0.4200
4:7434242:CA:C	donor_gain	0.4200
4:7430892:T:TA	donor_gain	0.3700
4:7431075:GATGA:G	donor_gain	0.3700
4:7432642:C:CC	acceptor_gain	0.3400
4:7432644:G:GT	acceptor_gain	0.3100
4:7432672:A:AA	acceptor_gain	0.3100
4:7434138:A:AG	acceptor_gain	0.3000
4:7434139:G:GG	acceptor_gain	0.3000
4:7434619:G:GT	donor_gain	0.3000
4:7430911:A:AG	donor_gain	0.2900
4:7430912:G:GG	donor_gain	0.2900
4:7432466:GC:G	acceptor_gain	0.2900
4:7433819:A:AG	donor_gain	0.2900
4:7432669:TG:T	acceptor_gain	0.2800

AlphaMissense

3423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:7433384:C:G	C499S	0.994
4:7433385:A:T	C499S	0.994
4:7433411:C:G	C490S	0.994
4:7433412:A:T	C490S	0.994
4:7433366:C:G	C505S	0.991
4:7433367:A:T	C505S	0.991
4:7433492:C:G	C463S	0.991
4:7433493:A:T	C463S	0.991
4:7433801:C:G	C360S	0.990
4:7433802:A:T	C360S	0.990
4:7433413:C:A	W489C	0.989
4:7433413:C:G	W489C	0.989
4:7433492:C:T	C463Y	0.989
4:7433801:C:T	C360Y	0.988
4:7433384:C:T	C499Y	0.987
4:7433567:C:G	C438S	0.986
4:7433568:A:T	C438S	0.986
4:7433600:C:G	C427S	0.986
4:7433601:A:T	C427S	0.986
4:7433365:G:C	C505W	0.985
4:7433493:A:G	C463R	0.985
4:7433684:C:G	C399S	0.985
4:7433685:A:T	C399S	0.985
4:7433693:C:G	C396S	0.984
4:7433694:A:T	C396S	0.984
4:7433873:C:G	C336S	0.984
4:7433874:A:T	C336S	0.984
4:7433684:C:T	C399Y	0.983
4:7433366:C:T	C505Y	0.982
4:7433435:C:G	C482S	0.982

dbSNP variants (sampled 300 via entrez): RS1000575562 (4:7436835 T>C), RS10011121 (4:7431833 C>A,T), RS1001240274 (4:7430722 C>T), RS10014338 (4:7432880 C>A), RS1001457003 (4:7430587 G>A,C,T), RS1001841890 (4:7431610 G>A), RS10021546 (4:7429901 C>A,T), RS10021616 (4:7429938 C>A,G), RS1002277369 (4:7431441 T>G), RS10023470 (4:7432729 A>G,T), RS1002465703 (4:7436405 C>A,T), RS1002678834 (4:7435512 G>A), RS10030127 (4:7431456 G>A,C,T), RS10032914 (4:7429914 A>C,G,T), RS1003302189 (4:7435852 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1788	Blood protein levels	3.000000e-88

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, affects methylation, decreases methylation	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
sodium arsenate	decreases expression, increases abundance	1
ethyl-p-hydroxybenzoate	increases expression	1
hydroquinone	increases expression	1
Arsenic	decreases expression, increases abundance	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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