NAP1L1

Summary

NAP1L1 (nucleosome assembly protein 1 like 1, HGNC:7637) is a protein-coding gene on chromosome 12q21.1, encoding Nucleosome assembly protein 1-like 1 (P55209). Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly.

This gene encodes a member of the nucleosome assembly protein (NAP) family. This protein participates in DNA replication and may play a role in modulating chromatin formation and contribute to the regulation of cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms; however, not all have been fully described.

Source: NCBI Gene 4673 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• MANE Select transcript: NM_004537

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7637
Approved symbol	NAP1L1
Name	nucleosome assembly protein 1 like 1
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	NRP, NAP1, NAP1L, MGC8688, MGC23410
Ensembl gene	ENSG00000187109
Ensembl biotype	protein_coding
OMIM	164060
Entrez	4673

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000393263, ENST00000431879, ENST00000535020, ENST00000542344, ENST00000544816, ENST00000547479, ENST00000547529, ENST00000547704, ENST00000547773, ENST00000547969, ENST00000547993, ENST00000548044, ENST00000548273, ENST00000549479, ENST00000549596, ENST00000549988, ENST00000550934, ENST00000551500, ENST00000551524, ENST00000551600, ENST00000551992, ENST00000552013, ENST00000552056, ENST00000552147, ENST00000552342, ENST00000618691, ENST00000880560, ENST00000880561, ENST00000880562, ENST00000880563, ENST00000916571, ENST00000916572, ENST00000951463, ENST00000951464, ENST00000951465

RefSeq mRNA: 5 — MANE Select: NM_004537 NM_001307924, NM_001330231, NM_001330232, NM_004537, NM_139207

CCDS: CCDS76581, CCDS81715, CCDS9013

Canonical transcript exons

ENST00000618691 — 15 exons

Exon	Start	End
ENSE00002421772	76084567	76084685
ENSE00003513689	76067371	76067473
ENSE00003535281	76060138	76060279
ENSE00003562945	76068909	76068994
ENSE00003579159	76049200	76049250
ENSE00003599586	76050531	76050653
ENSE00003611430	76056033	76056161
ENSE00003637939	76049756	76049785
ENSE00003685566	76059798	76059878
ENSE00003690648	76074203	76074239
ENSE00003729733	76053205	76053350
ENSE00003736093	76055019	76055090
ENSE00003741555	76053770	76053909
ENSE00003751878	76053091	76053110
ENSE00003754772	76036585	76048464

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 423.0038 / max 22225.4081, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132197	335.0769	1827
132196	68.7108	1814
132195	13.3567	1722
132194	2.6570	897
132191	1.2725	553
132184	0.9516	473
132182	0.6952	351
132190	0.1873	42
132198	0.0958	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.74	gold quality
ganglionic eminence	UBERON:0004023	99.72	gold quality
ventricular zone	UBERON:0003053	99.70	gold quality
embryo	UBERON:0000922	99.65	gold quality
secondary oocyte	CL:0000655	99.62	gold quality
tendon	UBERON:0000043	99.62	gold quality
ovary	UBERON:0000992	99.59	gold quality
left ovary	UBERON:0002119	99.58	gold quality
lower lobe of lung	UBERON:0008949	99.58	gold quality
right lung	UBERON:0002167	99.56	gold quality
right ovary	UBERON:0002118	99.50	gold quality
monocyte	CL:0000576	99.48	gold quality
lymph node	UBERON:0000029	99.48	gold quality
cartilage tissue	UBERON:0002418	99.48	gold quality
endometrium	UBERON:0001295	99.47	gold quality
germinal epithelium of ovary	UBERON:0001304	99.45	gold quality
tendon of biceps brachii	UBERON:0008188	99.44	gold quality
endocervix	UBERON:0000458	99.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.43	gold quality
body of uterus	UBERON:0009853	99.43	gold quality
medial globus pallidus	UBERON:0002477	99.40	gold quality
cortical plate	UBERON:0005343	99.40	gold quality
myometrium	UBERON:0001296	99.38	gold quality
uterus	UBERON:0000995	99.36	gold quality
tonsil	UBERON:0002372	99.36	gold quality
corpus callosum	UBERON:0002336	99.35	gold quality
mononuclear cell	CL:0000842	99.34	gold quality
leukocyte	CL:0000738	99.33	gold quality
globus pallidus	UBERON:0001875	99.33	gold quality
vena cava	UBERON:0004087	99.33	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	5442.15
E-GEOD-149689	yes	3738.88
E-MTAB-8142	yes	92.50
E-HCAD-4	yes	69.93
E-HCAD-5	yes	45.17
E-CURD-112	yes	41.33
E-MTAB-10553	yes	33.99
E-CURD-88	yes	30.72
E-GEOD-125970	yes	23.89
E-CURD-122	yes	23.54
E-HCAD-31	yes	22.02
E-HCAD-1	yes	21.03
E-MTAB-6701	yes	19.18
E-MTAB-9067	yes	14.17
E-MTAB-10042	yes	12.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

118 targeting NAP1L1, 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-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 23)

• These results suggest that the binding of sequence-specific DNA binding proteins to human nucleosome assembly protein 1 may be an important step contributing to the activation of transcription. (PMID:14966293)
• both the acidic nature of nucleosome assembly protein I and its other functional structure(s) may be essential to mediate the assembly and disassembly of the dimers in nucleosome core particles (PMID:16287874)
• Data show that Alien binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. (PMID:17339334)
• The biochemical properties of two human NAP1-like proteins, hNAP1L1 and hNAP1L4, were characterized. (PMID:20002496)
• Results identified several proteins interacting with NAP1L2, including the ubiquitously expressed members of the nucleosome assembly protein family, NAP1L1 and NAP1L4. (PMID:21333655)
• NAP1L1 was down-expressed following antiproliferative agent treatment in AuL12-treated cells in comparison with control and with Au(2)Phen-treated ovarian cancer cells. (PMID:22134777)
• TAF-Ibeta promotes BZLF1 expression and subsequent lytic infection by affecting chromatin at the BZLF1 promoter (PMID:23691099)
• Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. (PMID:24798879)
• NAP1L1 increases CSB processivity by decreasing the pausing probability during translocation. Our study, therefore, uncovers the different steps of CSB-mediated chromatin remodeling that can be regulated by NAP1L1. (PMID:28369616)
• Here the authors confirmed the hepatitis C virus NS5A-NAP1L1 interaction and mapped it to the C terminus of NS5A of both hepatitis C virus genotype 1 and 2. (PMID:28659470)
• knockdown of NAP1L1 suppresses IkappaBalpha degradation and nuclear transport of p65 subunit after treatment with TNF-a stimulation, leading to attenuation of the NF-kappaB transcriptional activity, whereas NAP1L4 knockdown remains silent.results of this study suggest that NAP1L1 downregulation renders the cell vulnerable to apoptotic cell death through attenuation of NF-kappaB transcriptional activity on the anti-apop… (PMID:28687276)
• In summary, the authors identified NAP1L1 as a novel binding partner of hepatitis c virus NS3 and found that the protease domain of NS3 is responsible for interactions with NAP1L1. They demonstrated the functional role of NAP1L1 in hepatitis c virus entry through regulating the protein expression of SR-B1. (PMID:29541944)
• Through regulating NAP1L1, PRDM8 inhibits PI3K/AKT/mTOR signaling in hepatocellular carcinoma. (PMID:29572888)
• Long non-coding RNAs (lncRNAs) CDKN2B-AS1 promoted nucleosome assembly protein 1 like 1 (NAP1L1) expression by sponging let-7c-5p in hepatocellular carcinoma (HCC) cells. (PMID:30165194)
• evaluated the currently known TBK1-mediated phosphorylation sites in the SKICH domains of NDP52 and TAX1BP1 on the basis of their interactions with NAP1 (PMID:30459273)
• The NAP1L1 regulates cell fate by controlling the expression of p53-responsive proarrest and proapoptotic genes through selective modulation of p53 acetylation at specific sites during normal homeostasis and in stress-induced responses. (PMID:31634504)
• Prognostic significance of NAP1L1 expression in patients with early lung adenocarcinoma. (PMID:32522932)
• NAP1L1 targeting suppresses the proliferation of nasopharyngeal carcinoma. (PMID:34563951)
• NAP1L1 promotes tumor proliferation through HDGF/C-JUN signaling in ovarian cancer. (PMID:35351053)
• A New Role of NAP1L1 in Megakaryocytes and Human Platelets. (PMID:36499021)
• Dynamic Solution Structures of Whole Human NAP1 Dimer Bound to One and Two Histone H2A-H2B Heterodimers Obtained by Integrative Methods. (PMID:37380014)
• Nucleosome assembly protein 1-like 1 (NAP1L1) in gastric cancer patients: a potential biomarker with diagnostic and prognostic utility. (PMID:38258494)
• NAP1L1 Promotes Endometrial Cancer Progression via EP300-Mediated DDX5 Promoter Acetylation. (PMID:38953887)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nap1l1	ENSDARG00000101813
mus_musculus	Nap1l1	ENSMUSG00000058799
rattus_norvegicus	Nap1l1	ENSRNOG00000003890

Paralogs (19): SET (ENSG00000119335), TSPY2 (ENSG00000168757), NAP1L5 (ENSG00000177432), TSPYL6 (ENSG00000178021), TSPYL5 (ENSG00000180543), TSPYL2 (ENSG00000184205), NAP1L3 (ENSG00000186310), NAP1L2 (ENSG00000186462), TSPYL4 (ENSG00000187189), TSPYL1 (ENSG00000189241), NAP1L4 (ENSG00000205531), TSPY3 (ENSG00000228927), TSPY8 (ENSG00000229549), SETSIP (ENSG00000230667), TSPY4 (ENSG00000233803), TSPY10 (ENSG00000236424), TSPY9 (ENSG00000238074), TSPY1 (ENSG00000258992), (ENSG00000293164)

Protein

Protein identifiers

Nucleosome assembly protein 1-like 1 — P55209 (reviewed: P55209)

Alternative names: Histone H2A-H2B chaperone NAP1L1, NAP-1-related protein

All UniProt accessions (17): B7Z4K9, B7Z9C2, P55209, F5H4R6, F8VRJ2, F8VUX1, F8VV59, F8VVB5, F8VXI6, F8VY35, F8W020, F8W0J6, F8W118, F8W543, H0YH88, H0YHC3, H0YIV4

UniProt curated annotations — full annotation on UniProt →

Function. Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly. Also participates in several important DNA repair mechanisms: greatly enhances ERCC6-mediated chromatin remodeling which is essential for transcription-coupled nucleotide excision DNA repair. Also stimulates homologous recombination (HR) by RAD51 and RAD54 which is essential in mitotic DNA double strand break (DSB) repair. Plays a key role in the regulation of embryonic neurogenesis. Promotes the proliferation of neural progenitors and inhibits neuronal differentiation during cortical development. Regulates neurogenesis via the modulation of RASSF10; regulates RASSF10 expression by promoting SETD1A-mediated H3K4 methylation at the RASSF10 promoter. (Microbial infection) Positively regulates Epstein-Barr virus reactivation in epithelial cells through the induction of viral BZLF1 expression. (Microbial infection) Together with human herpesvirus 8 protein LANA1, assists the proper assembly of the nucleosome on the replicated viral DNA.

Subunit / interactions. Homodimer. The dimer binds strongly and sequentially to single and double H2A-H2B heterodimers. Interacts with ERCC6; this interaction increases ERCC6 processivity. Interacts with RAD54. Interacts with SETD1A. (Microbial infection) Interacts with human herpesvirus 8 protein LANA1 (via N-terminus); this interaction is required for LANA1-dependent DNA replication. (Microbial infection) Interacts with hepatitis virus protein NS5A (via C-terminus); this interaction sequesters NAP1L1 in the cytoplasm, blocking its nuclear translocation. (Microbial infection) Interacts with Chikungunya virus non-structural protein 3 (via C-terminus).

Subcellular location. Nucleus. Chromosome. Melanosome. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Monoglycylated on glutamate residues. Cannot be polyglycylated due to the absence of functional TTLL10 in human. Polyglutamylated by TTLL4 on glutamate residues, resulting in polyglutamate chains on the gamma-carboxyl group. Both polyglutamylation and monoglycylation modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally.

Domain organisation. The NAP1L motif is required for the histone chaperone activity. The acidic domains are probably involved in the interaction with histones.

Similarity. Belongs to the nucleosome assembly protein (NAP) family.

Isoforms (3)

UniProt ID	Names	Canonical?
P55209-1	1	yes
P55209-2	2
P55209-3	3

RefSeq proteins (5): NP_001294853, NP_001317160, NP_001317161, NP_004528, NP_631946 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (49 total): modified residue 9, helix 8, strand 7, compositionally biased region 6, turn 4, splice variant 3, mutagenesis site 3, region of interest 3, short sequence motif 2, initiator methionine 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7BP5	X-RAY DIFFRACTION	1.9
11BD	X-RAY DIFFRACTION	3.2
11BC	ELECTRON MICROSCOPY	3.3
7UN6	ELECTRON MICROSCOPY	3.3
7UN3	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55209-F1	80.16	0.54

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 (10): 2, 10, 62, 64, 69, 116, 143, 388, 388, 1

Mutagenesis-validated functional residues (3):

Position	Phenotype
126	impaired binding to histones and ability to mediate histone chaperone activity.
130	impaired binding to histones and ability to mediate histone chaperone activity.
134	impaired binding to histones and ability to mediate histone chaperone activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 451 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, HORIUCHI_WTAP_TARGETS_DN, ACTACCT_MIR196A_MIR196B, MCLACHLAN_DENTAL_CARIES_UP, MODULE_151, GCM_NPM1, ATACCTC_MIR202, MORF_UBE2I, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, HSIAO_HOUSEKEEPING_GENES, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (6): DNA replication (GO:0006260), nucleosome assembly (GO:0006334), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), positive regulation of neurogenesis (GO:0050769), positive regulation of neural precursor cell proliferation (GO:2000179)

GO Molecular Function (5): chromatin binding (GO:0003682), RNA binding (GO:0003723), histone binding (GO:0042393), histone chaperone activity (GO:0140713), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020), melanosome (GO:0042470)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
DNA metabolic process	1
DNA biosynthetic process	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
positive regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
nucleic acid binding	1
protein binding	1
histone binding	1
protein carrier activity	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
pigment granule	1

Protein interactions and networks

STRING

2384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAP1L1	CDX4	O14627	762
NAP1L1	HNRNPU	Q00839	654
NAP1L1	H2BC21	Q16778	638
NAP1L1	NPM1	P06748	630
NAP1L1	MAGED2	Q9UNF1	597
NAP1L1	RBMX	P38159	589
NAP1L1	HNRNPA1	P09651	568
NAP1L1	NAP1L5	Q96NT1	566
NAP1L1	H2AX	P16104	533
NAP1L1	DGKZ	Q13574	517
NAP1L1	H2AJ	Q9BTM1	505
NAP1L1	HNRNPUL1	Q9BUJ2	497
NAP1L1	CREBBP	Q92793	488
NAP1L1	NUCLEOLIN	P19338	483
NAP1L1	HP1BP3	Q5SSJ5	466

IntAct

302 interactions, top by confidence:

A	B	Type	Score
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
ANP32E	H2AZ1	psi-mi:“MI:0915”(physical association)	0.770
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NAP1L4	NAP1L1	psi-mi:“MI:0915”(physical association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
	DDX3X	psi-mi:“MI:0914”(association)	0.630
JAK3	NAP1L1	psi-mi:“MI:0915”(physical association)	0.620
tat	NAP1L1	psi-mi:“MI:0915”(physical association)	0.580
NAP1L1	tat	psi-mi:“MI:0915”(physical association)	0.580
NAP1L1	GAS2L2	psi-mi:“MI:0915”(physical association)	0.560
NAP1L1	NAP1L2	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
H2AC11	PARP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (528): NAP1L1 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), RPL24 (Affinity Capture-MS), NAP1L4 (Affinity Capture-MS), MAGED2 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST2H2AB (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), FNTA (Affinity Capture-MS)

ESM2 similar proteins: A0A096LP55, A0A1D8PJT8, A1L243, A1L3N6, A6H767, A9ULB4, P00126, P00429, P05067, P07919, P08592, P12023, P13805, P14854, P23025, P27088, P28656, P36233, P36378, P48504, P55209, P56277, P79307, P99028, Q0P451, Q0VBY0, Q15545, Q28CA1, Q28EB4, Q2HJG8, Q4R374, Q4R5A5, Q4U0Y4, Q53CG4, Q5IS80, Q5M9I5, Q5R4D4, Q5R7L9, Q5RCT0, Q64267

Diamond homologs: A2ZX50, A6H767, B8AW64, B8B2R4, B8B4K9, B9FU45, F4JEI8, O19110, O59797, P25293, P28656, P51860, P53997, P55209, P78920, Q01105, Q01534, Q28EB4, Q2TA40, Q4U0Y4, Q53WK4, Q55ED1, Q5MGA9, Q5R4D4, Q5R675, Q5U2Z3, Q5VND6, Q63945, Q70Z16, Q70Z17, Q70Z18, Q70Z19, Q78ZA7, Q794H2, Q7ZY81, Q86VY4, Q8N831, Q8VD63, Q924R9, Q94K07

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 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
TNFR1-induced NF-kappa-B signaling pathway	5	11.9×	2e-03
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	5	10.9×	2e-03
Peptide chain elongation	11	9.9×	2e-06
Viral mRNA Translation	11	9.9×	2e-06
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	11	9.8×	2e-06
Regulation of TNFR1 signaling	6	9.5×	1e-03
Selenocysteine synthesis	11	9.4×	3e-06
Eukaryotic Translation Termination	11	9.4×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
extrinsic apoptotic signaling pathway via death domain receptors	6	13.8×	1e-03
tumor necrosis factor-mediated signaling pathway	7	13.2×	3e-04
cytoplasmic translation	12	12.7×	3e-07
positive regulation of type I interferon production	5	12.0×	9e-03
nucleosome assembly	12	9.6×	3e-06
heterochromatin formation	6	8.8×	9e-03
translation	13	7.6×	8e-06
DNA damage response	13	4.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2619 predictions. Top by Δscore:

Variant	Effect	Δscore
12:76047656:A:C	donor_gain	1.0000
12:76049781:TCATA:T	acceptor_gain	1.0000
12:76049782:CATA:C	acceptor_gain	1.0000
12:76049782:CATAC:C	acceptor_gain	1.0000
12:76049783:ATA:A	acceptor_gain	1.0000
12:76049784:TA:T	acceptor_gain	1.0000
12:76049785:ACTG:A	acceptor_loss	1.0000
12:76049786:C:CC	acceptor_gain	1.0000
12:76049786:CT:C	acceptor_loss	1.0000
12:76050527:TTA:T	donor_loss	1.0000
12:76050528:TACA:T	donor_loss	1.0000
12:76050529:A:AC	donor_gain	1.0000
12:76050529:ACAT:A	donor_gain	1.0000
12:76050529:ACATC:A	donor_loss	1.0000
12:76050530:C:CA	donor_gain	1.0000
12:76050530:CA:C	donor_gain	1.0000
12:76050530:CAT:C	donor_gain	1.0000
12:76050530:CATC:C	donor_gain	1.0000
12:76050530:CATCA:C	donor_gain	1.0000
12:76050649:TCATC:T	acceptor_gain	1.0000
12:76050650:CATC:C	acceptor_gain	1.0000
12:76050650:CATCC:C	acceptor_gain	1.0000
12:76050651:ATC:A	acceptor_gain	1.0000
12:76050652:TC:T	acceptor_gain	1.0000
12:76050652:TCCTA:T	acceptor_loss	1.0000
12:76050653:CC:C	acceptor_gain	1.0000
12:76050654:C:CC	acceptor_gain	1.0000
12:76050658:T:TC	acceptor_gain	1.0000
12:76050659:T:TC	acceptor_gain	1.0000
12:76050660:T:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000025562 (12:76084334 G>A), RS1000030196 (12:76048274 G>A), RS1000048849 (12:76053087 T>C,G), RS1000133232 (12:76061492 T>C), RS1000177672 (12:76066219 G>C), RS1000216825 (12:76038988 C>G,T), RS1000306579 (12:76072887 C>G,T), RS1000323627 (12:76067707 G>A,T), RS1000366697 (12:76073940 C>A,T), RS1000416639 (12:76079006 C>A,T), RS1000417103 (12:76041833 G>A), RS1000640585 (12:76074140 G>A,C), RS1000656834 (12:76045363 T>C), RS1000661148 (12:76052213 TTAACTAGAC>T), RS1000696793 (12:76065864 C>A,T)

Disease associations

OMIM: gene MIM:164060 | 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
GCST001762_603	Obesity-related traits	1.000000e-06
GCST012298_10	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067393 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.51	Kd	3102	nM	CHEMBL3752910
5.51	ED50	3102	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148820: Binding affinity to human NAP1L1 incubated for 45 mins by Kinobead based pull down assay	kd	3.1022	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
bisphenol A	increases expression, decreases expression, affects cotreatment	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Doxorubicin	affects expression, increases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression, decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
tamibarotene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651862	Binding	Binding affinity to human NAP1L1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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