APLP1

Summary

APLP1 (amyloid beta precursor like protein 1, HGNC:597) is a protein-coding gene on chromosome 19q13.12, encoding Amyloid beta precursor like protein 1 (P51693). May play a role in postsynaptic function.

This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 333 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_001024807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:597
Approved symbol	APLP1
Name	amyloid beta precursor like protein 1
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	APLP
Ensembl gene	ENSG00000105290
Ensembl biotype	protein_coding
OMIM	104775
Entrez	333

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 33 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000221891, ENST00000537454, ENST00000586861, ENST00000587274, ENST00000588808, ENST00000589298, ENST00000589743, ENST00000590561, ENST00000590926, ENST00000591165, ENST00000592316, ENST00000652533, ENST00000898020, ENST00000898021, ENST00000898022, ENST00000898023, ENST00000898024, ENST00000898025, ENST00000898026, ENST00000898027, ENST00000898028, ENST00000898029, ENST00000898030, ENST00000898031, ENST00000898032, ENST00000898033, ENST00000898034, ENST00000898035, ENST00000898036, ENST00000898037, ENST00000912739, ENST00000912740, ENST00000960045, ENST00000960046, ENST00000960047, ENST00000960048, ENST00000960049

RefSeq mRNA: 2 — MANE Select: NM_001024807 NM_001024807, NM_005166

CCDS: CCDS32997, CCDS92600

Canonical transcript exons

ENST00000221891 — 17 exons

Exon	Start	End
ENSE00000699119	35869667	35869810
ENSE00000862892	35868574	35868783
ENSE00003481926	35874741	35874869
ENSE00003483225	35876517	35876616
ENSE00003514045	35878890	35878952
ENSE00003530982	35879074	35879217
ENSE00003555094	35879343	35879792
ENSE00003562024	35878082	35878108
ENSE00003565832	35874504	35874662
ENSE00003575855	35871612	35871745
ENSE00003608678	35871237	35871349
ENSE00003636208	35877718	35877825
ENSE00003655675	35871858	35872036
ENSE00003665284	35873639	35873713
ENSE00003680193	35878584	35878654
ENSE00003680703	35872483	35872613
ENSE00003760164	35870896	35871028

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1604 / max 1292.6945, expressed in 1048 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175413	13.6329	1008
175414	3.0908	367
175415	1.0983	107
175416	0.5580	97
175417	0.3179	110
175418	0.2350	84
175411	0.2274	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.86	gold quality
inferior olivary complex	UBERON:0002127	99.73	gold quality
spinal cord	UBERON:0002240	99.73	gold quality
middle frontal gyrus	UBERON:0002702	99.72	gold quality
right frontal lobe	UBERON:0002810	99.71	gold quality
prefrontal cortex	UBERON:0000451	99.65	gold quality
caudate nucleus	UBERON:0001873	99.58	gold quality
nucleus accumbens	UBERON:0001882	99.51	gold quality
cortical plate	UBERON:0005343	99.49	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.45	gold quality
amygdala	UBERON:0001876	99.42	gold quality
hypothalamus	UBERON:0001898	99.40	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.36	gold quality
anterior cingulate cortex	UBERON:0009835	99.30	gold quality
cingulate cortex	UBERON:0003027	99.29	gold quality
inferior vagus X ganglion	UBERON:0005363	99.29	gold quality
corpus callosum	UBERON:0002336	99.28	gold quality
frontal cortex	UBERON:0001870	99.24	gold quality
frontal lobe	UBERON:0016525	99.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.22	gold quality
putamen	UBERON:0001874	99.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.19	gold quality
cerebellar hemisphere	UBERON:0002245	99.09	gold quality
cerebellar cortex	UBERON:0002129	99.05	gold quality
Ammon’s horn	UBERON:0001954	99.03	gold quality
telencephalon	UBERON:0001893	99.00	gold quality
forebrain	UBERON:0001890	98.99	gold quality
neocortex	UBERON:0001950	98.99	gold quality
postcentral gyrus	UBERON:0002581	98.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.92	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1571.82
E-HCAD-25	yes	51.08
E-GEOD-81547	yes	25.87
E-HCAD-5	yes	20.71
E-GEOD-84465	yes	14.35
E-GEOD-135922	yes	13.01
E-GEOD-93593	yes	12.17
E-GEOD-83139	yes	4.16
E-HCAD-10	yes	4.08
E-MTAB-10485	no	561.20
E-ENAD-27	no	3.27
E-HCAD-31	no	3.26
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

27 targeting APLP1, 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-4455	100.00	65.48	1587
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6757-5P	98.08	65.50	724
HSA-MIR-6827-3P	98.08	72.27	651
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-8083	95.93	67.55	694
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 23)

• APLP1 and APLP2 are processed by the gamma-secretase in a Presenilin 1-dependent manner and the extreme carboxyl-terminal fragments produced by this processing (APP-like Intracellular Domain) are able to enhance Fe65-dependent gene activation (PMID:12228233)
• APLP1 does not undergo the same type of regulated processing as APP and APLP2. (PMID:14597230)
• APLP1 and APLP2 and APP are processed similarly to act via the same nuclear target and are regulated by BACE 1 in neurons (PMID:14699153)
• APLP-1 and APLP-2 are processed by alpha- and gamma-secretase-like cleavages, and their intracellular domains can be released by cleavage at epsilon-sites. APLP-2 processing appears to be the most elaborate and to involve alternative cleavage sites. (PMID:14970212)
• The 5’ UTR of the Aplp1 gene lacks any type of CAGA box. This may explain its inability to form amyloid plaques. (PMID:15208260)
• APLP1 affects the endocytosis of APP and makes more APP available for alpha-secretase cleavage (PMID:16344553)
• These results suggest a possible role of APLP1 in regulation of alpha2A-adrenergic receptor trafficking. (PMID:16531006)
• APLP1 is differentially upregulated in gastrointestinal neuroendocrine tumours and may be important for the dissemination of small intestinal carcinoids (PMID:18430897)
• Coexpression of APP with APLP1 or APLP2 leads to diminished generation of Abeta42 (PMID:19126676)
• neither cell-derived nor chemically synthesized APLP1-derived peptide influences the oligomerization or aggregation of Abeta (PMID:19401174)
• Human cerebrospinal fluid contains three APLP1-derived Abeta-like peptides that are generated by beta- and gamma-cleavages at a concentration of approximately 4.5 nM. (PMID:20049724)
• Both APLP1 and APLP2, form transcriptionally active triple protein complexes with Mint3 and transcriptional co-activators Taz andYap. (PMID:21178287)
• The 2.1 A resolution electron density map reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. (PMID:21574595)
• [review] APP and its mammalian homologs, amyloid precursor-like proteins APLP1 and APLP2, participate under physiological conditions via trans-cellular dimerization in synaptogenesis. (PMID:21952790)
• APLP1 binds the II-III loop of the Ca(v)2.3 calcium channel and that this binding promotes internalization of the channel. (PMID:22178872)
• APLP1 has a regulatory role in the nuclear translocation of APP family intracellular domains due to the sequestration of Fe65. (PMID:23874953)
• CSF levels of 3 endogenous peptides derived from APLP1 (APL1beta25, APL1beta27 and APL1beta28) were decreased in Down syndrome. (PMID:24740518)
• APLP1 and APLP2, behave similarly to APP in that they both associate with assembled NMDA receptors in the endoplasmic reticulum (PMID:25683482)
• These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins. (PMID:25760599)
• The results show that in cognitively normal young adults carrying APlp1 mutations showed different spontaneous brain activity patterns without cerebral structural differences. (PMID:28987665)
• Results provide direct evidence that APLP1 functions as a neuronal zinc-dependent adhesion protein and allow a more detailed understanding of the molecular mechanisms driving the formation of APLP1 adhesion platforms. (PMID:29021345)
• The direct cleavage of APLP1 is a novel feature of the gamma-secretase. (PMID:29382944)
• Aplp1 interacts with Lag3 to facilitate transmission of pathologic alpha-synuclein. (PMID:38821932)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	aplp1	ENSDARG00000098368
mus_musculus	Aplp1	ENSMUSG00000006651
rattus_norvegicus	Aplp1	ENSRNOG00000020851
drosophila_melanogaster	Appl	FBGN0000108
caenorhabditis_elegans		WBGENE00000149

Paralogs (2): APLP2 (ENSG00000084234), APP (ENSG00000142192)

Protein

Protein identifiers

Amyloid beta precursor like protein 1 — P51693 (reviewed: P51693)

Alternative names: Amyloid beta (A4) precursor-like protein 1, Amyloid-like protein 1

All UniProt accessions (8): P51693, B7Z4G8, F5GZ08, K7ELK0, K7EMN4, K7EMS1, K7EQJ4, S4R3U6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding. Couples to JIP signal transduction through C-terminal binding. May interact with cellular G-protein signaling pathways. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis.

Subunit / interactions. Monomer and homodimer. Heparin binding promotes homodimerization. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB and APBA family members, MAPK8IP1 and DAB1. Binding to Dab1 inhibits its serine phosphorylation. Interacts with CPEB1. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif) with DAB1.

Subcellular location. Cell membrane Cytoplasm.

Tissue specificity. Expressed in the cerebral cortex where it is localized to the postsynaptic density (PSD).

Post-translational modifications. Proteolytically cleaved by caspases during neuronal apoptosis. Cleaved, in vitro, at Asp-620 by caspase-3. N- and O-glycosylated. O-glycosylation with core 1 or possibly core 8 glycans. Glycosylation on Ser-227 is the preferred site to Thr-228.

Domain organisation. The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The NPXY site is also involved in clathrin-mediated endocytosis.

Miscellaneous. Binds zinc and copper in the extracellular domain. Zinc-binding increases heparin binding. No Cu(2+) reducing activity with copper-binding.

Similarity. Belongs to the APP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51693-1	1	yes
P51693-2	2

RefSeq proteins (2): NP_001019978, NP_005157 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008154	Amyloid_glyco_extra	Domain
IPR008155	Amyloid_glyco	Family
IPR011178	Amyloid_glyco_Cu-bd	Domain
IPR015849	Amyloid_glyco_heparin-bd	Domain
IPR019543	APP_amyloid_C	Domain
IPR019744	APP_CUBD_CS	Conserved_site
IPR019745	Amyloid_glyco_intracell_CS	Conserved_site
IPR024329	Amyloid_glyco_E2_domain	Domain
IPR036176	E2_sf	Homologous_superfamily
IPR036454	Amyloid_glyco_heparin-bd_sf	Homologous_superfamily
IPR036669	Amyloid_Cu-bd_sf	Homologous_superfamily

Pfam: PF02177, PF10515, PF12924, PF12925

UniProt features (59 total): region of interest 10, helix 7, binding site 6, glycosylation site 6, disulfide bond 6, short sequence motif 3, mutagenesis site 3, compositionally biased region 2, topological domain 2, sequence conflict 2, strand 2, turn 2, domain 2, signal peptide 1, chain 1, peptide 1, site 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3PMR	X-RAY DIFFRACTION	2.11
3Q7L	X-RAY DIFFRACTION	2.2
3QMK	X-RAY DIFFRACTION	2.21
3Q7G	X-RAY DIFFRACTION	2.3
4RDA	X-RAY DIFFRACTION	2.5
4RD9	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51693-F1	69.36	0.34

Functional residue map

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

Catalytic / active sites (1): 620–621 (cleavage; by caspase-3)

Ligand- & substrate-binding residues (6): 174; 206; 209; 210; 561; 561

Disulfide bonds (6): 60–84, 95–140, 120–128, 156–210, 167–197, 181–209

Glycosylation sites (6): 215, 227, 228, 337, 461, 551

Mutagenesis-validated functional residues (3):

Position	Phenotype
426	reduced affinity for heparin. reduces homodimerization.
429	strongly reduced affinity for heparin. strongly reduced homodimerization.
433	reduced affinity for heparin. reduces homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 218 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GRUETZMANN_PANCREATIC_CANCER_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, AP2_Q3, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_FOREBRAIN_DEVELOPMENT, TANG_SENESCENCE_TP53_TARGETS_UP, GOBP_TRANSLATION, MODULE_66, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (14): regulation of translation (GO:0006417), endocytosis (GO:0006897), apoptotic process (GO:0006915), cell adhesion (GO:0007155), nervous system development (GO:0007399), axonogenesis (GO:0007409), central nervous system development (GO:0007417), animal organ morphogenesis (GO:0009887), extracellular matrix organization (GO:0030198), forebrain development (GO:0030900), cellular response to norepinephrine stimulus (GO:0071874), negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0106072), cytosolic mRNA polyadenylation (GO:0180011), animal organ development (GO:0048513)

GO Molecular Function (8): heparin binding (GO:0008201), alpha-2A adrenergic receptor binding (GO:0031694), alpha-2B adrenergic receptor binding (GO:0031695), alpha-2C adrenergic receptor binding (GO:0031696), identical protein binding (GO:0042802), transition metal ion binding (GO:0046914), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): basement membrane (GO:0005604), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
adrenergic receptor binding	3
system development	2
anatomical structure development	2
cytoplasm	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
nervous system development	1
anatomical structure morphogenesis	1
animal organ development	1
extracellular structure organization	1
external encapsulating structure organization	1
brain development	1
cellular response to catecholamine stimulus	1
response to norepinephrine	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
mRNA metabolic process	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein binding	1
metal ion binding	1
binding	1
cation binding	1
extracellular matrix	1
nuclear lumen	1
endomembrane system	1

Protein interactions and networks

STRING

2232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APLP1	APBB1	O00213	925
APLP1	CNTN5	O94779	832
APLP1	BACE1	P56817	799
APLP1	APBA1	Q02410	717
APLP1	PSEN1	P49768	709
APLP1	APBB2	Q92870	691
APLP1	CTSB	P07858	681
APLP1	ADAM10	O14672	667
APLP1	PSENEN	Q9NZ42	653
APLP1	PSEN2	P49810	649
APLP1	MAPK8IP1	Q9UQF2	644
APLP1	NCSTN	Q92542	643
APLP1	C12orf57	Q99622	628
APLP1	APH1A	Q96BI3	622
APLP1	PRNP	P04156	614

IntAct

70 interactions, top by confidence:

A	B	Type	Score
APBB2	APP	psi-mi:“MI:0914”(association)	0.830
APLP1	APLP1	psi-mi:“MI:0407”(direct interaction)	0.680
APLP1	APLP1	psi-mi:“MI:0915”(physical association)	0.680
VPS29	APLP1	psi-mi:“MI:0915”(physical association)	0.560
TK1	APLP1	psi-mi:“MI:0915”(physical association)	0.550
APLP1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.550
APLP1	APP	psi-mi:“MI:0915”(physical association)	0.540
APLP2	APLP1	psi-mi:“MI:0915”(physical association)	0.540
APLP1	APP	psi-mi:“MI:0407”(direct interaction)	0.540
APLP1	APLP2	psi-mi:“MI:0407”(direct interaction)	0.540
GLP1R	APLP1	psi-mi:“MI:0915”(physical association)	0.540
APLP1	GLP1R	psi-mi:“MI:0915”(physical association)	0.540
GLP1R	APLP1	psi-mi:“MI:0403”(colocalization)	0.540
APBB3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
APLP1	ZNF24	psi-mi:“MI:0915”(physical association)	0.510
CNTN3	APLP1	psi-mi:“MI:0407”(direct interaction)	0.440
APLP1	CNTN4	psi-mi:“MI:0407”(direct interaction)	0.440
APLP1	CNTN5	psi-mi:“MI:0407”(direct interaction)	0.440
APLP1	MED12	psi-mi:“MI:0407”(direct interaction)	0.440
MED12	APLP1	psi-mi:“MI:0407”(direct interaction)	0.440
APLP1	Slc5a7	psi-mi:“MI:0915”(physical association)	0.400
PILRA	APLP1	psi-mi:“MI:0915”(physical association)	0.400
SPON1	APLP1	psi-mi:“MI:0915”(physical association)	0.400
APLP1	Tom1	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	APLP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (67): APLP1 (Affinity Capture-MS), APLP1 (Affinity Capture-MS), APLP1 (Affinity Capture-MS), APLP1 (Affinity Capture-MS), APLP1 (Two-hybrid), APLP1 (Affinity Capture-Western), APLP1 (Affinity Capture-Western), APLP1 (Affinity Capture-Western), APLP1 (Two-hybrid), APLP1 (Two-hybrid), APLP1 (Two-hybrid), APLP1 (Two-hybrid), UTP14A (Two-hybrid), APLP1 (Two-hybrid), APLP1 (Two-hybrid)

ESM2 similar proteins: A0MLS4, A2BD09, A2D4U1, A2D670, A2T6K4, O14669, P01257, P01286, P02818, P02820, P02822, P27916, P41547, P51693, P63292, P70160, P84348, P84349, P84350, Q03157, Q0VCT2, Q2NL23, Q3KNT9, Q3TYX2, Q5HZE8, Q5T124, Q60549, Q64375, Q6AYE5, Q6BEG6, Q6BEG7, Q71SY6, Q76IQ4, Q7M742, Q7TNI2, Q86UD1, Q8JFY4, Q8K2B0, Q8QZR4, Q8R182

Diamond homologs: A0A6P8HC43, A5X2X1, A8Y7N6, A8Y7N7, A8Y7N9, A8Y7P1, A8Y7P5, B2BS84, B2ZBB6, B5KL30, B5KL33, B5KL38, B5KL39, B5L5Q8, B5L5R1, B5L5R4, B6ZIW0, C0HK74, C0HLB2, C0HMC7, C1IC53, E5AJX3, E7FL12, E7FL13, F6ULY1, F8J2F3, F8J2F4, O35536, O43278, O43291, O73683, O76840, O93279, O95925, P00991, P00992, P00994, P05067, P08592, P0DJ66

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
synapse organization	5	27.0×	6e-04
axonogenesis	5	15.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2284 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35869791:TGCTG:T	donor_gain	1.0000
19:35869792:GCTGG:G	donor_gain	1.0000
19:35869795:G:GT	donor_gain	1.0000
19:35870892:CCAGA:C	acceptor_loss	1.0000
19:35870893:CAG:C	acceptor_loss	1.0000
19:35870894:A:AC	acceptor_loss	1.0000
19:35870894:A:AG	acceptor_gain	1.0000
19:35870894:AGAT:A	acceptor_gain	1.0000
19:35870895:G:GC	acceptor_gain	1.0000
19:35870895:GAT:G	acceptor_gain	1.0000
19:35870895:GATG:G	acceptor_gain	1.0000
19:35870895:GATGT:G	acceptor_gain	1.0000
19:35871027:GC:G	donor_gain	1.0000
19:35871029:G:GG	donor_gain	1.0000
19:35871235:A:AG	acceptor_gain	1.0000
19:35871235:AGCT:A	acceptor_gain	1.0000
19:35871236:G:GG	acceptor_gain	1.0000
19:35871236:GCT:G	acceptor_gain	1.0000
19:35871236:GCTG:G	acceptor_gain	1.0000
19:35871338:G:GT	donor_gain	1.0000
19:35871347:G:GT	donor_gain	1.0000
19:35871355:G:GT	donor_gain	1.0000
19:35871464:GGATC:G	donor_gain	1.0000
19:35871465:GATC:G	donor_gain	1.0000
19:35871856:A:AG	acceptor_gain	1.0000
19:35871856:AGT:A	acceptor_gain	1.0000
19:35871857:G:GG	acceptor_gain	1.0000
19:35871857:GT:G	acceptor_gain	1.0000
19:35871857:GTG:G	acceptor_gain	1.0000
19:35871982:G:GT	donor_gain	1.0000

AlphaMissense

4211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35871285:T:G	F158C	1.000
19:35873651:T:A	W332R	1.000
19:35873651:T:C	W332R	1.000
19:35873653:G:C	W332C	1.000
19:35873653:G:T	W332C	1.000
19:35874507:T:C	F354L	1.000
19:35874508:T:C	F354S	1.000
19:35874509:C:A	F354L	1.000
19:35874509:C:G	F354L	1.000
19:35874520:T:C	L358P	1.000
19:35869741:G:C	W74C	0.999
19:35869741:G:T	W74C	0.999
19:35872560:T:C	F310L	0.999
19:35872561:T:C	F310S	0.999
19:35872562:C:A	F310L	0.999
19:35872562:C:G	F310L	0.999
19:35873652:G:C	W332S	0.999
19:35873654:G:C	A333P	0.999
19:35873660:G:C	A335P	0.999
19:35874508:T:G	F354C	0.999
19:35874562:T:C	L372P	0.999
19:35871278:T:A	C156S	0.998
19:35871279:G:C	C156S	0.998
19:35871284:T:C	F158L	0.998
19:35871285:T:C	F158S	0.998
19:35871286:C:A	F158L	0.998
19:35871286:C:G	F158L	0.998
19:35872569:G:C	A313P	0.998
19:35872582:T:C	L317P	0.998
19:35872591:G:C	R320P	0.998

dbSNP variants (sampled 300 via entrez): RS1000550115 (19:35879872 C>T), RS1000617363 (19:35879804 G>A), RS1000770322 (19:35873088 G>A), RS1000809243 (19:35867147 G>A,C), RS1000863069 (19:35867596 C>T), RS1000928022 (19:35867498 T>C), RS1001037152 (19:35873242 A>C), RS1001222394 (19:35873398 C>T), RS1001538874 (19:35878288 G>A), RS1001594231 (19:35878739 C>T), RS1002229575 (19:35872862 TTTG>T,TTTGTTG), RS1002579005 (19:35872576 T>A,C), RS1002594094 (19:35877226 C>T), RS1003022773 (19:35870498 A>G), RS1003174908 (19:35870989 G>A,T)

Disease associations

OMIM: gene MIM:104775 | 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
GCST003123_32	Severe influenza A (H1N1) infection	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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
Benzo(a)pyrene	increases expression, increases methylation	3
Doxorubicin	increases expression	3
Valproic Acid	affects expression, increases expression	3
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
nickel acetate	decreases expression, decreases reaction, increases expression	1
pyrimidifen	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, affects localization	1
Dactinomycin	increases expression, affects cotreatment	1
Edetic Acid	affects localization, decreases reaction	1
Estradiol	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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