NAP1L3

Summary

NAP1L3 (nucleosome assembly protein 1 like 3, HGNC:7639) is a protein-coding gene on chromosome Xq21.32, encoding Nucleosome assembly protein 1-like 3 (Q99457). Histone chaperone.

This gene is intronless and encodes a member of the nucleosome assembly protein (NAP) family. This gene is linked closely to a region of genes responsible for several X-linked cognitive disability syndromes.

Source: NCBI Gene 4675 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 53 total — 1 pathogenic
• MANE Select transcript: NM_004538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7639
Approved symbol	NAP1L3
Name	nucleosome assembly protein 1 like 3
Location	Xq21.32
Locus type	gene with protein product
Status	Approved
Aliases	MB20, NPL3, MGC26312
Ensembl gene	ENSG00000186310
Ensembl biotype	protein_coding
OMIM	300117
Entrez	4675

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000373079, ENST00000475430

RefSeq mRNA: 1 — MANE Select: NM_004538 NM_004538

CCDS: CCDS14465

Canonical transcript exons

ENST00000373079 — 1 exons

Exon	Start	End
ENSE00001459467	93670930	93673578

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9549 / max 976.0458, expressed in 966 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199891	10.5499	877
199893	0.5906	181
199892	0.3821	170
199890	0.3053	171
209752	0.1269	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.18	gold quality
superior vestibular nucleus	UBERON:0007227	99.06	gold quality
pons	UBERON:0000988	98.97	gold quality
endothelial cell	CL:0000115	98.79	gold quality
substantia nigra pars compacta	UBERON:0001965	98.77	gold quality
superior frontal gyrus	UBERON:0002661	98.47	gold quality
parietal lobe	UBERON:0001872	98.46	gold quality
postcentral gyrus	UBERON:0002581	98.42	gold quality
cerebellar vermis	UBERON:0004720	98.41	gold quality
occipital lobe	UBERON:0002021	98.38	gold quality
primary visual cortex	UBERON:0002436	98.36	gold quality
orbitofrontal cortex	UBERON:0004167	98.24	gold quality
entorhinal cortex	UBERON:0002728	98.08	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.83	gold quality
lateral globus pallidus	UBERON:0002476	97.77	gold quality
ventral tegmental area	UBERON:0002691	97.68	gold quality
prefrontal cortex	UBERON:0000451	97.66	gold quality
hypothalamus	UBERON:0001898	97.58	gold quality
middle temporal gyrus	UBERON:0002771	97.52	gold quality
medulla oblongata	UBERON:0001896	97.51	gold quality
frontal pole	UBERON:0002795	97.48	gold quality
cortical plate	UBERON:0005343	97.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.19	gold quality
cerebral cortex	UBERON:0000956	96.97	gold quality
cerebellum	UBERON:0002037	96.97	gold quality
frontal cortex	UBERON:0001870	96.86	gold quality
cerebellar cortex	UBERON:0002129	96.84	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	14.68
E-GEOD-84465	yes	6.93
E-ANND-3	no	2.65
E-HCAD-5	no	2.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting NAP1L3, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-605-3P	99.88	69.22	1833

Literature-anchored findings (GeneRIF, showing 2)

• we demonstrate that HOXA3 and HOXA5 genes are markedly upregulated when NAP1L3 is suppressed in umbilical cord blood (UCB) haematopoietic stem cells (HSCs). Taken together, our findings establish an important role for NAP1L3 in haematopoietic stem cells homeostasis and haematopoietic differentiation. (PMID:30046127)
• Nucleosome Assembly Protein 1-Like 3 Enhances Cisplatin Resistance of Ovarian Cancer Cell by Activating Transforming Growth Factor-Beta Pathway. (PMID:32701410)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspy	ENSDARG00000005015
danio_rerio	nap1l4a	ENSDARG00000070560
mus_musculus	Nap1l3	ENSMUSG00000055733
rattus_norvegicus	Nap1l3	ENSRNOG00000029087
drosophila_melanogaster	Set	FBGN0014879
drosophila_melanogaster	Nap1	FBGN0015268
drosophila_melanogaster	CG3708	FBGN0040345
drosophila_melanogaster	mil	FBGN0267366
caenorhabditis_elegans		WBGENE00005007
caenorhabditis_elegans		WBGENE00017075

Paralogs (19): SET (ENSG00000119335), TSPY2 (ENSG00000168757), NAP1L5 (ENSG00000177432), TSPYL6 (ENSG00000178021), TSPYL5 (ENSG00000180543), TSPYL2 (ENSG00000184205), NAP1L2 (ENSG00000186462), NAP1L1 (ENSG00000187109), 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 3 — Q99457 (reviewed: Q99457)

Alternative names: Histone chaperone NAP1L3

All UniProt accessions (2): Q99457, V9GYL6

UniProt curated annotations — full annotation on UniProt →

Function. Histone chaperone. May play a role in cellular differentiation.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_004529* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (9 total): compositionally biased region 3, region of interest 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99457-F1	66.19	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GNF2_RTN1, FREAC2_01, BROWNE_HCMV_INFECTION_6HR_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MODULE_66, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MCLACHLAN_DENTAL_CARIES_DN, MODULE_99, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN

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

GO Molecular Function (3): chromatin binding (GO:0003682), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
protein binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAP1L3	MAGEB2	O15479	493
NAP1L3	BEX1	Q9HBH7	452
NAP1L3	PNPLA4	P41247	448
NAP1L3	PPP1R1A	Q13522	422
NAP1L3	GABRB3	P28472	395
NAP1L3	OR4N5	Q8IXE1	394
NAP1L3	RGS7	P49802	387
NAP1L3	OR4K14	Q8NGD5	370
NAP1L3	COMMD1	Q8N668	354
NAP1L3	RASGRP3	Q8IV61	348
NAP1L3	SPATA25	Q9BR10	313
NAP1L3	ZNF496	Q96IT1	309
NAP1L3	SMCO4	Q9NRQ5	305
NAP1L3	TM6SF1	Q9BZW5	304
NAP1L3	BEX2	Q9BXY8	303

IntAct

49 interactions, top by confidence:

A	B	Type	Score
NAP1L2	NAP1L3	psi-mi:“MI:0915”(physical association)	0.670
NAP1L3	NAP1L2	psi-mi:“MI:0915”(physical association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
TSPYL1	PCM1	psi-mi:“MI:0914”(association)	0.640
NAP1L3	DNM2	psi-mi:“MI:0915”(physical association)	0.560
NAP1L3	GFAP	psi-mi:“MI:0915”(physical association)	0.560
NAP1L3	MECP2	psi-mi:“MI:0915”(physical association)	0.560
NAP1L3	NDUFV2	psi-mi:“MI:0915”(physical association)	0.560
NAP1L3	JPH3	psi-mi:“MI:0915”(physical association)	0.560
FAM9A	AP3B1	psi-mi:“MI:0914”(association)	0.530
TSPYL1	GPC3	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
NAP1L3	PPIB	psi-mi:“MI:0915”(physical association)	0.400
NAP1L3	BEND7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (30): TSPYL4 (Two-hybrid), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Two-hybrid), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-RNA), NAP1L3 (Proximity Label-MS), NAP1L3 (Proximity Label-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS)

ESM2 similar proteins: A0A286Y9D1, A1L162, A1Z1Q3, A2VCV0, A6QQ66, A8KBE0, A8MQG7, B3NLX1, B4F6Q9, B4GT53, B4P6W7, O75496, O88513, O94880, P32447, P51860, Q02508, Q12373, Q16RY9, Q2T9W9, Q2TBJ0, Q3UYG8, Q4VA55, Q504Y3, Q5F471, Q5H9R7, Q5ZMS4, Q65Z40, Q66H73, Q6CN69, Q6DD45, Q6PAV8, Q6PG04, Q794H2, Q7Z5K2, Q8INT5, Q8LF97, Q8N4S0, Q8NI08, Q8VDY9

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564866	GRCh37/hg19 Xq21.31-21.33(chrX:86794810-96275443)x1	Pathogenic

SpliceAI

35 predictions. Top by Δscore:

Variant	Effect	Δscore
X:93672131:A:T	acceptor_gain	0.9400
X:93672130:C:T	acceptor_gain	0.9300
X:93672130:C:CT	acceptor_gain	0.9000
X:93671974:C:CC	acceptor_gain	0.8300
X:93671973:A:AC	acceptor_gain	0.7700
X:93672124:C:T	acceptor_gain	0.7100
X:93672347:T:G	acceptor_gain	0.6700
X:93672124:C:CT	acceptor_gain	0.6300
X:93673259:C:CT	acceptor_gain	0.4000
X:93673259:C:T	acceptor_gain	0.4000
X:93671965:TCA:T	acceptor_gain	0.3600
X:93672872:C:A	acceptor_gain	0.3600
X:93673367:A:AC	donor_gain	0.3600
X:93673368:C:CC	donor_gain	0.3600
X:93671981:AGTTG:A	acceptor_gain	0.3500
X:93672873:A:AA	acceptor_gain	0.3500
X:93671971:GGA:G	acceptor_gain	0.3200
X:93671982:GTTG:G	acceptor_gain	0.3200
X:93672346:T:TG	acceptor_gain	0.3200
X:93672887:TG:T	acceptor_gain	0.3000
X:93671972:GA:G	acceptor_gain	0.2500
X:93671980:AAGTT:A	acceptor_gain	0.2400
X:93672115:T:G	acceptor_gain	0.2300
X:93672892:TC:T	acceptor_gain	0.2300
X:93672874:T:TA	acceptor_gain	0.2200
X:93672875:A:AA	acceptor_gain	0.2200
X:93673362:G:GT	donor_gain	0.2200
X:93673369:G:C	donor_gain	0.2200
X:93672871:T:TA	acceptor_gain	0.2100
X:93672880:G:GA	acceptor_gain	0.2100

AlphaMissense

3410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:93672089:A:G	W406R	0.997
X:93672089:A:T	W406R	0.997
X:93672087:C:A	W406C	0.995
X:93672087:C:G	W406C	0.995
X:93672180:C:A	K375N	0.995
X:93672180:C:G	K375N	0.995
X:93672362:A:G	W315R	0.995
X:93672362:A:T	W315R	0.995
X:93672973:A:G	L111P	0.995
X:93672985:C:G	R107P	0.995
X:93672202:A:G	F368S	0.994
X:93672220:A:G	F362S	0.994
X:93672986:G:T	R107S	0.994
X:93672219:A:C	F362L	0.993
X:93672219:A:T	F362L	0.993
X:93672221:A:G	F362L	0.993
X:93672225:A:C	F360L	0.993
X:93672225:A:T	F360L	0.993
X:93672226:A:G	F360S	0.993
X:93672227:A:G	F360L	0.993
X:93671890:A:G	L472S	0.992
X:93671912:C:G	D465H	0.992
X:93672176:A:C	Y377D	0.992
X:93672973:A:T	L111H	0.992
X:93672994:A:T	V104D	0.992
X:93671900:C:A	G469W	0.991
X:93672104:C:G	G401R	0.991
X:93672295:A:G	L337P	0.991
X:93671878:A:T	V476D	0.990
X:93671899:C:T	G469E	0.990

dbSNP variants (sampled 300 via entrez): RS1001253882 (X:93671039 C>T), RS1001994084 (X:93674648 T>C), RS1002288948 (X:93671512 G>A), RS1003326723 (X:93673944 T>C), RS1003402836 (X:93671716 T>C), RS1003598345 (X:93673650 C>G), RS1004047936 (X:93673188 G>A), RS1004454674 (X:93670938 G>A,C), RS1004484822 (X:93673599 C>G,T), RS1004507236 (X:93671614 C>T), RS1008154675 (X:93671717 T>C), RS1008801684 (X:93673544 G>A), RS1009216574 (X:93675105 G>C), RS1010366086 (X:93673032 C>A,T), RS1011656331 (X:93671075 A>G)

Disease associations

OMIM: gene MIM:300117 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1265	Metabolite levels	9.000000e-07
GCST009391_1422	Metabolite levels	2.000000e-06
GCST009391_733	Metabolite levels	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010545	uridine diphosphate measurement
EFO:0010452	adenosine diphosphate measurement
EFO:0009774	serine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Haloperidol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Nickel	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression	1

Clinical trials (associated diseases)

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