NAP1L4

Summary

NAP1L4 (nucleosome assembly protein 1 like 4, HGNC:7640) is a protein-coding gene on chromosome 11p15.4, encoding Nucleosome assembly protein 1-like 4 (Q99733). Acts as a histone chaperone in nucleosome assembly.

This gene encodes a member of the nucleosome assembly protein (NAP) family which can interact with both core and linker histones. It can shuttle between the cytoplasm and nucleus, suggesting a role as a histone chaperone. This gene is one of several located near the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer.

Source: NCBI Gene 4676 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 76 total
• Druggable target: yes
• MANE Select transcript: NM_005969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7640
Approved symbol	NAP1L4
Name	nucleosome assembly protein 1 like 4
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	NAP2
Ensembl gene	ENSG00000205531
Ensembl biotype	protein_coding
OMIM	601651
Entrez	4676

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 72 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000380542, ENST00000399614, ENST00000430811, ENST00000448187, ENST00000455338, ENST00000469089, ENST00000469805, ENST00000483643, ENST00000492594, ENST00000492685, ENST00000526023, ENST00000526115, ENST00000526842, ENST00000528261, ENST00000528363, ENST00000528968, ENST00000529361, ENST00000530064, ENST00000531291, ENST00000532325, ENST00000534372, ENST00000620138, ENST00000703798, ENST00000867767, ENST00000867768, ENST00000867769, ENST00000867770, ENST00000867771, ENST00000867772, ENST00000867773, ENST00000867774, ENST00000867775, ENST00000867776, ENST00000867777, ENST00000867778, ENST00000867779, ENST00000867780, ENST00000867781, ENST00000867782, ENST00000867783, ENST00000867784, ENST00000867785, ENST00000867786, ENST00000867787, ENST00000867788, ENST00000867789, ENST00000867790, ENST00000867791, ENST00000867792, ENST00000867793, ENST00000867794, ENST00000867795, ENST00000867796, ENST00000935408, ENST00000935409, ENST00000935410, ENST00000935411, ENST00000935412, ENST00000935413, ENST00000935414, ENST00000935415, ENST00000935416, ENST00000935417, ENST00000955341, ENST00000955342, ENST00000955343, ENST00000955344, ENST00000955345, ENST00000955346, ENST00000955347, ENST00000955348, ENST00000955349, ENST00000955350, ENST00000955351, ENST00000955352, ENST00000955353, ENST00000955354, ENST00000955355, ENST00000955356, ENST00000955357

RefSeq mRNA: 14 — MANE Select: NM_005969 NM_001369375, NM_001369376, NM_001369377, NM_001369378, NM_001369379, NM_001369380, NM_001369381, NM_001369382, NM_001369383, NM_001369384, NM_001369385, NM_001369386, NM_001369388, NM_005969

CCDS: CCDS41599, CCDS91410

Canonical transcript exons

ENST00000380542 — 16 exons

Exon	Start	End
ENSE00001485415	2971448	2971534
ENSE00001485417	2972102	2972243
ENSE00001485421	2979207	2979237
ENSE00001680525	2964680	2964751
ENSE00001882089	2944437	2945646
ENSE00003500245	2976024	2976123
ENSE00003501833	2959770	2959909
ENSE00003590359	2949227	2949264
ENSE00003616642	2954527	2954646
ENSE00003638020	2978284	2978342
ENSE00003640125	2958399	2958544
ENSE00003647775	2951259	2951315
ENSE00003673513	2951780	2951809
ENSE00003692374	2955744	2955766
ENSE00003784554	2969803	2969934
ENSE00003989948	2992254	2992329

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 98.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.2447 / max 908.5516, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118262	44.1019	1814
118264	3.8385	1537
118260	3.4859	1532
118259	2.1611	1181
118261	1.4834	904
118263	1.1449	833
118256	0.0290	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.42	gold quality
ganglionic eminence	UBERON:0004023	98.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.27	gold quality
cortical plate	UBERON:0005343	98.16	gold quality
calcaneal tendon	UBERON:0003701	97.94	gold quality
left testis	UBERON:0004533	97.92	gold quality
right testis	UBERON:0004534	97.90	gold quality
bone marrow cell	CL:0002092	97.82	gold quality
sural nerve	UBERON:0015488	97.82	gold quality
apex of heart	UBERON:0002098	97.54	gold quality
muscle of leg	UBERON:0001383	97.51	gold quality
colonic epithelium	UBERON:0000397	97.49	gold quality
gastrocnemius	UBERON:0001388	97.48	gold quality
minor salivary gland	UBERON:0001830	97.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.44	gold quality
adenohypophysis	UBERON:0002196	97.33	gold quality
anterior cingulate cortex	UBERON:0009835	97.33	gold quality
cerebellar hemisphere	UBERON:0002245	97.32	gold quality
lower esophagus	UBERON:0013473	97.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.30	gold quality
right frontal lobe	UBERON:0002810	97.29	gold quality
adrenal tissue	UBERON:0018303	97.29	gold quality
vermiform appendix	UBERON:0001154	97.22	gold quality
right atrium auricular region	UBERON:0006631	97.22	gold quality
cerebellar cortex	UBERON:0002129	97.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.17	gold quality
rectum	UBERON:0001052	97.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

70 targeting NAP1L4, 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-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-10394-5P	99.65	66.83	1852

Literature-anchored findings (GeneRIF, showing 9)

• NAP-2 is in complex(es) with other proteins, which are distinct from histones (PMID:15368365)
• Human Nap2 promotes nucleosome assembly with H3t/H4. (PMID:18281699)
• The biochemical properties of two human NAP1-like proteins, hNAP1L1 and hNAP1L4, were characterized. (PMID:20002496)
• Telomeric NAP1L4 and OSBPL5 of the KCNQ1 cluster, and the DECORIN gene are not imprinted in human trophoblast stem cells. (PMID:20644730)
• Results identified several proteins interacting with NAP1L2, including the ubiquitously expressed members of the nucleosome assembly protein family, NAP1L1 and NAP1L4. (PMID:21333655)
• 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)
• The NAP1L4 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)
• Nucleosome assembly protein 1-like 4, a new therapeutic target for proliferation and invasion of melanoma cells. (PMID:33583643)
• Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes. (PMID:34120636)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nap1l4b	ENSDARG00000068868
mus_musculus	Nap1l4	ENSMUSG00000059119
rattus_norvegicus	Nap1l4	ENSRNOG00000020615

Paralogs (19): SET (ENSG00000119335), TSPY2 (ENSG00000168757), NAP1L5 (ENSG00000177432), TSPYL6 (ENSG00000178021), TSPYL5 (ENSG00000180543), TSPYL2 (ENSG00000184205), NAP1L3 (ENSG00000186310), NAP1L2 (ENSG00000186462), NAP1L1 (ENSG00000187109), TSPYL4 (ENSG00000187189), TSPYL1 (ENSG00000189241), TSPY3 (ENSG00000228927), TSPY8 (ENSG00000229549), SETSIP (ENSG00000230667), TSPY4 (ENSG00000233803), TSPY10 (ENSG00000236424), TSPY9 (ENSG00000238074), TSPY1 (ENSG00000258992), (ENSG00000293164)

Protein

Protein identifiers

Nucleosome assembly protein 1-like 4 — Q99733 (reviewed: Q99733)

Alternative names: Histone chaperone NAP1L4, Nucleosome assembly protein 2

All UniProt accessions (14): A0A994J3W0, A8MXH2, C9J1B1, C9J6D1, C9JZI7, E9PJJ2, E9PKI2, E9PKT8, E9PNJ7, E9PNW0, E9PP22, E9PS34, Q99733, H0YCI4

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a histone chaperone in nucleosome assembly.

Subunit / interactions. Interacts with core (H2A, CD2APH2B, H3, H4) and linker (H1) histones. (Microbial infection) Interacts with Chikungunya virus non-structural protein 3 (via C-terminus).

Subcellular location. Nucleus. Chromosome. Cytoplasm.

Tissue specificity. Ubiquitous. Biallelically expressed in fetal and adult tissues. Highest levels in testis.

Post-translational modifications. Phosphorylated at the G0/G1 boundary but it is not phosphorylated in S-phase. Phosphorylated protein remains in the cytoplasm in a complex with histones during the G0/G1 transition, whereas dephosphorylation triggers its transport into the nucleus at the G1/S-boundary. Polyglutamylated by TTLL4, a modification that occurs exclusively on glutamate residues and results in polyglutamate chains on the gamma-carboxyl group. Some residues may also be monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q99733-1	1	yes
Q99733-2	2, NAP1L4b

RefSeq proteins (14): NP_001356304, NP_001356305, NP_001356306, NP_001356307, NP_001356308, NP_001356309, NP_001356310, NP_001356311, NP_001356312, NP_001356313, NP_001356314, NP_001356315, NP_001356317, NP_005960* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (22 total): modified residue 12, region of interest 3, compositionally biased region 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99733-F1	81.28	0.57

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 (12): 7, 12, 51, 53, 54, 58, 105, 125, 146, 304, 2, 5

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (1): nucleosome assembly (GO:0006334)

GO Molecular Function (6): chromatin binding (GO:0003682), RNA binding (GO:0003723), nucleosome binding (GO:0031491), histone binding (GO:0042393), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), dendrite (GO:0030425), neuronal cell body (GO:0043025)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
nucleic acid binding	1
chromatin binding	1
protein-containing complex binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAP1L4	PHLDA2	Q53GA4	813
NAP1L4	CDKN1C	P49918	701
NAP1L4	MRPL23	Q16540	677
NAP1L4	SLC67A1	Q96BI1	671
NAP1L4	DGKZ	Q13574	666
NAP1L4	TSSC4	Q9Y5U2	600
NAP1L4	KCNQ1	P51787	598
NAP1L4	OSBPL5	Q9H0X9	597
NAP1L4	ASCL2	Q99929	595
NAP1L4	DYNC1I2	Q13409	594
NAP1L4	ZNF214	Q9UL59	588
NAP1L4	ZNF215	Q9UL58	588
NAP1L4	H2BC21	Q16778	575
NAP1L4	NSD1	Q96L73	542
NAP1L4	IGF2	P01344	533

IntAct

136 interactions, top by confidence:

A	B	Type	Score
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
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
Cep78	UBR5	psi-mi:“MI:0915”(physical association)	0.560
tat	AHCYL1	psi-mi:“MI:0914”(association)	0.560
NAP1L4	tat	psi-mi:“MI:0915”(physical association)	0.560
H2AC11	PARP1	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
NAP1L5	RPS2	psi-mi:“MI:0914”(association)	0.530
NAP1L1	RPL17	psi-mi:“MI:0914”(association)	0.530
MAGED2	GNAL	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
CEP78	CEP43	psi-mi:“MI:0914”(association)	0.530
NAP1L1	FNTB	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
NAP1L1	H2AC11	psi-mi:“MI:0914”(association)	0.530
LRRK2	DFFA	psi-mi:“MI:0914”(association)	0.530
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
	MYL12B	psi-mi:“MI:0914”(association)	0.460
NAP1L4	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
JAK3	BAG2	psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Cep78	ING5	psi-mi:“MI:0914”(association)	0.350
ASPM		psi-mi:“MI:0914”(association)	0.350

BioGRID (295): NAP1L4 (Affinity Capture-RNA), NAP1L4 (Affinity Capture-RNA), NAP1L4 (Affinity Capture-RNA), NAP1L4 (Affinity Capture-MS), NAP1L4 (Reconstituted Complex), NAP1L4 (Affinity Capture-MS), NAP1L4 (Affinity Capture-RNA), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation), NAP1L4 (Co-fractionation)

ESM2 similar proteins: A2XU85, A2ZX50, A6H767, B8AEC1, B8AW64, B8B2R4, B8B4K9, B9FU45, F4JEI8, O42584, O59797, P06748, P07222, P13825, P25293, P28656, P51860, P53853, P53997, P54397, P55209, P78920, Q18240, Q1HTZ9, Q28EB4, Q2TA40, Q3T160, Q4U0Y4, Q53WK4, Q55ED1, Q5AAI8, Q5MGA9, Q5R4D4, Q5U2Z3, Q5VND6, Q69JW2, Q70Z16, Q70Z17, Q70Z18, Q70Z19

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 180 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
Deposition of new CENPA-containing nucleosomes at the centromere	7	9.2×	1e-03
Packaging Of Telomere Ends	5	9.1×	5e-03
Influenza Viral RNA Transcription and Replication	5	8.9×	5e-03
Signaling by ALK fusions and activated point mutants	7	8.7×	1e-03
FXIIa activates plasma kallikrein-kinin system	6	8.6×	2e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	8.4×	6e-03
Cleavage of the damaged purine	5	8.4×	6e-03
Transcriptional regulation of granulopoiesis	8	8.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	8	9.4×	9e-04
nucleosome assembly	9	8.1×	9e-04
translation	10	6.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3404 predictions. Top by Δscore:

Variant	Effect	Δscore
11:2951255:CAA:C	donor_loss	1.0000
11:2951256:AAC:A	donor_loss	1.0000
11:2951258:CCTT:C	donor_loss	1.0000
11:2951314:TCC:T	acceptor_loss	1.0000
11:2951315:CCTG:C	acceptor_loss	1.0000
11:2951316:CTGT:C	acceptor_loss	1.0000
11:2951317:T:C	acceptor_loss	1.0000
11:2951806:CAAA:C	acceptor_gain	1.0000
11:2951810:C:CC	acceptor_gain	1.0000
11:2954525:A:AC	donor_gain	1.0000
11:2954526:C:CC	donor_gain	1.0000
11:2954646:CCT:C	acceptor_loss	1.0000
11:2954648:T:A	acceptor_loss	1.0000
11:2955765:TG:T	acceptor_gain	1.0000
11:2955767:C:CC	acceptor_gain	1.0000
11:2969798:CTTA:C	donor_loss	1.0000
11:2969799:TTA:T	donor_loss	1.0000
11:2969800:TA:T	donor_loss	1.0000
11:2969801:A:AC	donor_gain	1.0000
11:2969801:ACCT:A	donor_loss	1.0000
11:2969802:C:CC	donor_gain	1.0000
11:2969802:C:G	donor_loss	1.0000
11:2969802:CCTGG:C	donor_gain	1.0000
11:2969931:CTCC:C	acceptor_gain	1.0000
11:2969932:TCC:T	acceptor_gain	1.0000
11:2969933:CC:C	acceptor_gain	1.0000
11:2969933:CCC:C	acceptor_gain	1.0000
11:2969934:CC:C	acceptor_gain	1.0000
11:2969934:CCTAA:C	acceptor_loss	1.0000
11:2969935:C:CC	acceptor_gain	1.0000

AlphaMissense

2507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:2954579:A:T	V328D	1.000
11:2954603:C:T	G320E	1.000
11:2954604:C:G	G320R	1.000
11:2954604:C:T	G320R	1.000
11:2958457:T:A	R278S	1.000
11:2958457:T:G	R278S	1.000
11:2958458:C:G	R278T	1.000
11:2958529:C:A	W254C	1.000
11:2958529:C:G	W254C	1.000
11:2958531:A:G	W254R	1.000
11:2958531:A:T	W254R	1.000
11:2959795:C:G	G241R	1.000
11:2959904:A:C	F204L	1.000
11:2959904:A:T	F204L	1.000
11:2959906:A:G	F204L	1.000
11:2964723:A:G	L188P	1.000
11:2969850:A:G	W163R	1.000
11:2969850:A:T	W163R	1.000
11:2972165:G:C	F84L	1.000
11:2972165:G:T	F84L	1.000
11:2972166:A:G	F84S	1.000
11:2972167:A:G	F84L	1.000
11:2954570:G:T	A331D	0.999
11:2954582:A:C	I327R	0.999
11:2954582:A:T	I327K	0.999
11:2954585:C:G	R326P	0.999
11:2954591:C:G	R324P	0.999
11:2954592:G:T	R324S	0.999
11:2954603:C:A	G320V	0.999
11:2954611:A:C	F317L	0.999

dbSNP variants (sampled 300 via entrez): RS1000005175 (11:2969462 G>A,T), RS1000046712 (11:2966214 G>C), RS1000077871 (11:2966012 A>G), RS1000222533 (11:2944264 G>A), RS1000301354 (11:2986835 C>T), RS1000301894 (11:2950926 A>G), RS1000309466 (11:2964581 G>C,T), RS1000327253 (11:2993692 A>G), RS1000347165 (11:2976672 C>T), RS1000359164 (11:2959979 CACA>C), RS1000379658 (11:2976446 T>A,C), RS1000423324 (11:2960538 G>A), RS1000460796 (11:2981559 T>A,C), RS1000579109 (11:2979998 T>C), RS1000681463 (11:2975447 T>G)

Disease associations

OMIM: gene MIM:601651 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000769_7	Calcium levels	5.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55
GCST90002381_294	Eosinophil count	5.000000e-14
GCST90002382_378	Eosinophil percentage of white cells	6.000000e-17
GCST90002393_349	Monocyte count	1.000000e-09
GCST90002398_192	Neutrophil count	6.000000e-14
GCST90002401_175	Platelet distribution width	2.000000e-12
GCST90002407_321	White blood cell count	2.000000e-12
GCST90011899_6	Aspartate aminotransferase levels	2.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0007984	platelet component distribution width
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3886061 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.04	Kd	9202	nM	CHEMBL3752910
5.04	ED50	9202	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 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	2148821: Binding affinity to human NAP1L4 incubated for 45 mins by Kinobead based pull down assay	kd	9.2016	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, decreases expression, increases expression, affects cotreatment	4
Tobacco Smoke Pollution	increases expression, affects expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, decreases expression	1
benzo(e)pyrene	increases methylation	1
cupric oxide	increases phosphorylation	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
bisphenol S	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Clozapine	increases expression	1
Coumestrol	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects expression	1
Estradiol	increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Gallic Acid	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3881405	Binding	Inhibition of human Nap2B expressed in HEK293 cells assessed as inhibition of Pi uptake measured after 23 mins in presence of [33P]orthophosphoric acid by TopCount scintillation counting method	NHE3-binding compounds and methods for inhibiting phosphate transport

Clinical trials (associated diseases)

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