NAP1L5

Summary

NAP1L5 (nucleosome assembly protein 1 like 5, HGNC:19968) is a protein-coding gene on chromosome 4q22.1, encoding Nucleosome assembly protein 1-like 5 (Q96NT1).

This gene encodes a protein that shares sequence similarity to nucleosome assembly factors, but may be localized to the cytoplasm rather than the nucleus. Expression of this gene is downregulated in hepatocellular carcinomas. This gene is located within a differentially methylated region (DMR) and is imprinted and paternally expressed. There is a related pseudogene on chromosome 4.

Source: NCBI Gene 266812 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• MANE Select transcript: NM_153757

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19968
Approved symbol	NAP1L5
Name	nucleosome assembly protein 1 like 5
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DRLM
Ensembl gene	ENSG00000177432
Ensembl biotype	protein_coding
OMIM	612203
Entrez	266812

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000323061

RefSeq mRNA: 1 — MANE Select: NM_153757 NM_153757

CCDS: CCDS3632

Canonical transcript exons

ENST00000323061 — 1 exons

Exon	Start	End
ENSE00001244607	88695913	88697829

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1517 / max 861.2169, expressed in 1472 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53106	12.3658	1429
53107	1.0736	450
53105	0.6168	222
53102	0.0955	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.91	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.85	gold quality
middle temporal gyrus	UBERON:0002771	99.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.56	gold quality
substantia nigra pars compacta	UBERON:0001965	99.50	gold quality
pons	UBERON:0000988	99.34	gold quality
superior vestibular nucleus	UBERON:0007227	99.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.26	gold quality
cerebellar vermis	UBERON:0004720	99.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.90	gold quality
ventral tegmental area	UBERON:0002691	98.86	gold quality
superior frontal gyrus	UBERON:0002661	98.75	gold quality
entorhinal cortex	UBERON:0002728	98.63	gold quality
medulla oblongata	UBERON:0001896	98.62	gold quality
parietal lobe	UBERON:0001872	98.61	gold quality
postcentral gyrus	UBERON:0002581	98.52	gold quality
occipital lobe	UBERON:0002021	98.38	gold quality
primary visual cortex	UBERON:0002436	98.30	gold quality
dorsal root ganglion	UBERON:0000044	98.00	gold quality
hypothalamus	UBERON:0001898	97.66	gold quality
lateral globus pallidus	UBERON:0002476	97.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.31	gold quality
prefrontal cortex	UBERON:0000451	97.27	gold quality
frontal cortex	UBERON:0001870	96.91	gold quality
cerebral cortex	UBERON:0000956	96.81	gold quality
neocortex	UBERON:0001950	96.64	gold quality
temporal lobe	UBERON:0001871	96.54	gold quality
anterior cingulate cortex	UBERON:0009835	96.29	gold quality
midbrain	UBERON:0001891	95.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	10.12
E-GEOD-84465	yes	6.82
E-ANND-3	yes	3.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting NAP1L5, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1468-3P	99.96	72.74	3797
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-767-5P	99.95	70.85	993
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-605-3P	99.88	69.22	1833

Literature-anchored findings (GeneRIF, showing 1)

• NAP1L5 facilitates pancreatic ductal adenocarcinoma progression via TRIM29-mediated ubiquitination of PHLPP1. (PMID:37717692)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspy	ENSDARG00000005015
danio_rerio	nap1l4a	ENSDARG00000070560
mus_musculus	Nap1l5	ENSMUSG00000055430
rattus_norvegicus	Nap1l5	ENSRNOG00000083613
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), TSPYL6 (ENSG00000178021), TSPYL5 (ENSG00000180543), TSPYL2 (ENSG00000184205), NAP1L3 (ENSG00000186310), 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 5 — Q96NT1 (reviewed: Q96NT1)

Alternative names: Down-regulated in liver malignancy, Histone chaperone NAP1L5

All UniProt accessions (1): Q96NT1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Predominantly expressed in brain.

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

RefSeq proteins (1): NP_715638* (*=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 4, region of interest 2, chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NT1-F1	66.85	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): RRAGTTGT_UNKNOWN, NKX25_02, FOXO4_01, CAGCTG_AP4_Q5, GTGCCTT_MIR506, ACATTCC_MIR1_MIR206, AACTTT_UNKNOWN, chr4q22, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, DBP_Q6, GOBP_CHROMATIN_REMODELING, TTTNNANAGCYR_UNKNOWN, NKX3A_01, FOXO4_02, TGGAAA_NFAT_Q4_01

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

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAP1L5	MCTS2	A0A3B3IRV3	720
NAP1L5	NNAT	Q16517	680
NAP1L5	PEG10	Q86TG7	673
NAP1L5	HERC3	Q15034	670
NAP1L5	H0Y8G9	H0Y8G9	666
NAP1L5	SNRPN	P14648	630
NAP1L5	ZFP57	Q9NU63	629
NAP1L5	PLAGL1	Q9UM63	625
NAP1L5	MEST	Q5EB52	603
NAP1L5	COMMD1	Q8N668	601
NAP1L5	PPP1R26	Q5T8A7	587
NAP1L5	PEG3	P78418	585
NAP1L5	GNAS	Q5JWF2	571
NAP1L5	NAP1L1	P55209	566
NAP1L5	NDN	Q99608	557

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CSNK2B	NMT2	psi-mi:“MI:0914”(association)	0.660
NAP1L5	IQGAP1	psi-mi:“MI:0914”(association)	0.640
NAP1L5	NAP1L2	psi-mi:“MI:0915”(physical association)	0.630
NAP1L2	NAP1L5	psi-mi:“MI:0915”(physical association)	0.630
ATF4	NAP1L5	psi-mi:“MI:0915”(physical association)	0.560
SYCE2	NAP1L5	psi-mi:“MI:0915”(physical association)	0.560
SNRPB2	NAP1L5	psi-mi:“MI:0915”(physical association)	0.560
NAP1L5	RPS2	psi-mi:“MI:0914”(association)	0.530
TMEM97	STXBP3	psi-mi:“MI:0914”(association)	0.530
IFNA8	IFIT3	psi-mi:“MI:0914”(association)	0.530
NAP1L1	H2AC11	psi-mi:“MI:0914”(association)	0.530
ADM	NAP1L5	psi-mi:“MI:0915”(physical association)	0.400
MTNR1A	NAP1L5	psi-mi:“MI:0915”(physical association)	0.370
CMBL	H2BC11	psi-mi:“MI:0914”(association)	0.350
DFFA	NAP1L5	psi-mi:“MI:0915”(physical association)	0.000
NAP1L5	ATF4	psi-mi:“MI:0915”(physical association)	0.000
NAP1L2	NAP1L5	psi-mi:“MI:0915”(physical association)	0.000
SYCE2	NAP1L5	psi-mi:“MI:0915”(physical association)	0.000
SNRPB2	NAP1L5	psi-mi:“MI:0915”(physical association)	0.000
NAP1L5	SYCE2	psi-mi:“MI:0915”(physical association)	0.000
NAP1L5	GRB2	psi-mi:“MI:0915”(physical association)	0.000
IKBKG	NAP1L5	psi-mi:“MI:0407”(direct interaction)	0.000
NAP1L5	KAT5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (84): NAP1L1 (Affinity Capture-MS), RPS2 (Affinity Capture-MS), NDEL1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), ABT1 (Affinity Capture-MS), CCDC102A (Affinity Capture-MS), RRP7A (Affinity Capture-MS), NOL6 (Affinity Capture-MS), SKA1 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), FAM207A (Affinity Capture-MS), EVL (Affinity Capture-MS), RNF138 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS)

ESM2 similar proteins: A3LXX5, A5DLG8, A5E145, A5PLC8, A6ZQX9, F4K4Y5, O49595, P01252, P02313, P02314, P02316, P04550, P05114, P05204, P06302, P06454, P08814, P09602, P12274, P12902, P16527, P17691, P18608, P20962, P26350, P40019, P80272, P91753, Q10020, Q15651, Q1RMM5, Q3ZBV4, Q59RN6, Q5R4H5, Q5R715, Q5R790, Q5RAA0, Q5U274, Q5ZIR5, Q68F55

Diamond homologs: A2ZX50, A6H767, A6NFF2, B8AW64, B8B2R4, B8B4K9, B9FU45, F4JEI8, O59797, O88852, P25293, P28656, P51860, P55209, P78920, Q18240, Q1RMM5, Q28EB4, Q2TA40, Q4U0Y4, Q53WK4, Q55ED1, Q5AAI8, Q5MGA9, Q5PPG6, Q5R4D4, Q5R4H5, Q5R5G8, Q5R675, Q5U2Z3, Q5VND6, Q70Z16, Q70Z17, Q70Z18, Q70Z19, Q78ZA7, Q794H2, Q7ZY81, Q8N831, Q8VD63

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

52 predictions. Top by Δscore:

Variant	Effect	Δscore
4:88696771:C:CC	acceptor_gain	0.8100
4:88696300:GCT:G	acceptor_gain	0.7300
4:88696770:A:AC	acceptor_gain	0.7200
4:88697209:CTT:C	donor_gain	0.5800
4:88697208:A:AC	donor_gain	0.5700
4:88697209:C:CC	donor_gain	0.5700
4:88696301:C:A	acceptor_gain	0.4900
4:88696664:A:AG	acceptor_gain	0.4900
4:88696783:A:C	acceptor_gain	0.4800
4:88697211:T:TA	donor_gain	0.4800
4:88696782:C:CT	acceptor_gain	0.4300
4:88696525:TGACA:T	acceptor_gain	0.4200
4:88696526:GACAG:G	acceptor_gain	0.4200
4:88697210:T:C	donor_gain	0.4000
4:88696932:T:TG	acceptor_gain	0.3900
4:88696302:T:A	acceptor_gain	0.3800
4:88696780:GTCA:G	donor_gain	0.3800
4:88696781:TCAT:T	donor_gain	0.3800
4:88697753:A:C	acceptor_gain	0.3700
4:88696527:ACAG:A	acceptor_gain	0.3500
4:88696778:ATGT:A	acceptor_gain	0.3500
4:88696299:AGC:A	acceptor_gain	0.3400
4:88696769:CA:C	acceptor_gain	0.3300
4:88696528:CAG:C	acceptor_gain	0.3200
4:88697752:CATGT:C	acceptor_gain	0.3200
4:88697403:C:T	donor_gain	0.3100
4:88696766:CTGCA:C	acceptor_gain	0.2900
4:88696780:GTCAT:G	acceptor_gain	0.2900
4:88696530:G:T	acceptor_gain	0.2800
4:88696779:TGTC:T	acceptor_gain	0.2800

AlphaMissense

1215 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:88697441:A:G	L105P	1.000
4:88697461:A:C	F98L	1.000
4:88697461:A:T	F98L	1.000
4:88697462:A:G	F98S	1.000
4:88697463:A:G	F98L	1.000
4:88697492:T:G	Q88P	1.000
4:88697504:A:G	L84P	1.000
4:88697504:A:T	L84H	1.000
4:88697387:A:G	L123P	0.999
4:88697396:A:C	I120S	0.999
4:88697396:A:G	I120T	0.999
4:88697405:A:G	L117P	0.999
4:88697429:T:C	Y109C	0.999
4:88697429:T:G	Y109S	0.999
4:88697430:A:C	Y109D	0.999
4:88697430:A:G	Y109H	0.999
4:88697441:A:T	L105Q	0.999
4:88697449:A:C	F102L	0.999
4:88697449:A:T	F102L	0.999
4:88697450:A:G	F102S	0.999
4:88697451:A:G	F102L	0.999
4:88697462:A:C	F98C	0.999
4:88697463:A:C	F98V	0.999
4:88697463:A:T	F98I	0.999
4:88697469:C:G	A96P	0.999
4:88697474:A:T	I94K	0.999
4:88697495:A:G	L87P	0.999
4:88697513:A:T	V81D	0.999
4:88697516:C:G	R80P	0.999
4:88697517:G:C	R80G	0.999

dbSNP variants (sampled 300 via entrez): RS1000895558 (4:88699439 T>G), RS1001161230 (4:88697758 AGAG>A), RS1001213706 (4:88697992 C>T), RS1002932270 (4:88696551 C>T), RS1005326998 (4:88696469 A>T), RS1005372904 (4:88696811 C>T), RS1005434328 (4:88698017 A>G), RS1006888109 (4:88699505 A>G), RS1007645043 (4:88698588 C>T), RS1007697323 (4:88698731 A>C,G), RS1007978741 (4:88697590 G>T), RS1009049760 (4:88695730 T>G), RS1010231284 (4:88698781 CCCA>C), RS1010419470 (4:88695635 A>G), RS1013666840 (4:88699476 A>G)

Disease associations

OMIM: gene MIM:612203 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003478_2	Hair greying	9.000000e-06
GCST005956_59	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST005957_14	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-06
GCST005962_35	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-08
GCST008139_1	Gout	4.000000e-35
GCST90020024_703	A body shape index	3.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	9
trichostatin A	affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	increases expression, affects expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Camptothecin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Quercetin	decreases expression	1
Rifampin	increases expression	1
Testosterone	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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