NASP

Summary

NASP (nuclear autoantigenic sperm protein, HGNC:7644) is a protein-coding gene on chromosome 1p34.1, encoding Nuclear autoantigenic sperm protein (P49321). Component of the histone chaperone network. It is a selective cancer dependency (DepMap: 40.6% of cell lines).

This gene encodes a H1 histone binding protein that is involved in transporting histones into the nucleus of dividing cells. Multiple isoforms are encoded by transcript variants of this gene. The somatic form is expressed in all mitotic cells, is localized to the nucleus, and is coupled to the cell cycle. The testicular form is expressed in embryonic tissues, tumor cells, and the testis. In male germ cells, this protein is localized to the cytoplasm of primary spermatocytes, the nucleus of spermatids, and the periacrosomal region of mature spermatozoa.

Source: NCBI Gene 4678 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 130 total
• GTEx eGene: eQTL in 14 tissues, sQTL in 6 (q < 0.05)
• Cancer dependency (DepMap): dependent in 40.6% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.39 (moderately constrained)
• MANE Select transcript: NM_002482
• Interaction hub: 1,932 STRING partners (top 8% of genes corpus-wide)
• Notable: 130 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7644
Approved symbol	NASP
Name	nuclear autoantigenic sperm protein
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	FLB7527, FLJ31599, FLJ35510, MGC19722, MGC20372, MGC2297, DKFZp547F162, PRO1999
Ensembl gene	ENSG00000132780
Ensembl biotype	protein_coding
OMIM	603185
Entrez	4678

Gene structure

Transcript identifiers

Ensembl transcripts: 84 — 51 protein_coding, 27 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000350030

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 8, TSL 3: 4, TSL 4: 4, TSL 5: 7

ENST00000350030, ENST00000351223, ENST00000372052, ENST00000437362, ENST00000437901, ENST00000453748, ENST00000464190, ENST00000470768, ENST00000472408, ENST00000481782, ENST00000525515, ENST00000527359, ENST00000527470, ENST00000527932, ENST00000528084, ENST00000528238, ENST00000529333, ENST00000530073, ENST00000530840, ENST00000531532, ENST00000531612, ENST00000534101, ENST00000534450, ENST00000537798, ENST00000629893, ENST00000858824, ENST00000858825, ENST00000858826, ENST00000858827, ENST00000858828, ENST00000858829, ENST00000858830, ENST00000923964, ENST00000923965, ENST00000923966, ENST00000923967, ENST00000923968, ENST00000923969, ENST00000923970, ENST00000923971, ENST00000923972, ENST00000923973, ENST00000923974, ENST00000923975, ENST00000923976, ENST00000923977, ENST00000923978, ENST00000923979, ENST00000923980, ENST00000923981, ENST00000961668, ENST00000961669, ENST00000974479, ENST00000974480, ENST00000974481, ENST00001052299, ENST00001052300, ENST00001052301, ENST00001070513, ENST00001070518, ENST00001070531, ENST00001070532, ENST00001070533, ENST00001070534, ENST00001101225, ENST00001101226, ENST00001101227, ENST00001101228, ENST00001101229, ENST00001101230, ENST00001101231, ENST00001101232, ENST00001101233, ENST00001101234, ENST00001101235, ENST00001101236, ENST00001101237, ENST00001101238, ENST00001101239, ENST00001101240, ENST00001101241, ENST00001101242, ENST00001101243, ENST00001145635

RefSeq mRNA: 3 — MANE Select: NM_002482 NM_001195193, NM_002482, NM_152298

CCDS: CCDS524, CCDS525, CCDS55597

Canonical transcript exons

ENST00000350030 — 15 exons

Exon	Start	End
ENSE00001815639	45618061	45618893
ENSE00003470022	45604936	45605016
ENSE00003478736	45615013	45615201
ENSE00003487994	45606482	45606591
ENSE00003490574	45584041	45584205
ENSE00003511854	45591223	45591270
ENSE00003512169	45616626	45616703
ENSE00003548507	45613169	45613248
ENSE00003568340	45614096	45614181
ENSE00003586112	45607321	45608337
ENSE00003595072	45615305	45615471
ENSE00003614735	45614293	45614366
ENSE00003672570	45617463	45617591
ENSE00003677926	45616337	45616393
ENSE00003680489	45602255	45602365

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.0967 / max 1408.6541, expressed in 1793 samples.

Highest expression (Bgee): ventricular zone, embryo, ganglionic eminence, oocyte, testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NASP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	6.6e-07	+0.13	1:45611756:G:C
Cells Cultured fibroblasts	eqtl	1.4e-03	-0.05	1:45698302:T:A
Artery Tibial	eqtl	6.1e-03	-0.10	1:45429219:G:T
Artery Aorta	sqtl	8.7e-03	+0.95	1:45826853:G:A
Skin Sun Exposed Lower leg	sqtl	1.4e-02	+0.24	1:45024221:G:C
Brain Cerebellar Hemisphere	eqtl	1.6e-02	+0.46	1:44681063:C:T
Heart Atrial Appendage	eqtl	2.3e-02	+0.15	1:45567628:T:C
Small Intestine Terminal Ileum	eqtl	2.8e-02	-0.49	1:46488836:AC:A
Artery Aorta	eqtl	3.2e-02	+0.15	1:45571288:T:C
Esophagus Muscularis	sqtl	3.2e-02	+0.71	1:45573343:A:G
Esophagus Muscularis	eqtl	3.3e-02	-0.22	1:46527531:A:G
Liver	eqtl	3.4e-02	+0.27	1:45325482:G:A
Skin Not Sun Exposed Suprapubic	sqtl	3.6e-02	+0.32	1:45557684:A:T
Thyroid	eqtl	3.6e-02	-0.43	1:44672301:A:G
Esophagus Gastroesophageal Junction	eqtl	3.6e-02	-0.12	1:44974313:A:C
Whole Blood	eqtl	4.5e-02	+0.10	1:46138643:G:A
Artery Tibial	sqtl	4.5e-02	+0.63	1:45573343:A:G
Brain Putamen basal ganglia	eqtl	4.7e-02	+0.56	1:44632259:C:T
Skin Not Sun Exposed Suprapubic	eqtl	4.7e-02	-0.31	1:46333550:A:G
Muscle Skeletal	sqtl	5.0e-02	+0.20	1:45666201:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
2695	42.0038	1793
201498	0.0929	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.49	gold quality
embryo	UBERON:0000922	99.35	gold quality
ganglionic eminence	UBERON:0004023	99.27	gold quality
oocyte	CL:0000023	99.08	gold quality
right testis	UBERON:0004534	98.78	gold quality
left testis	UBERON:0004533	98.67	gold quality
secondary oocyte	CL:0000655	98.60	gold quality
sural nerve	UBERON:0015488	98.56	gold quality
cortical plate	UBERON:0005343	98.16	gold quality
right ovary	UBERON:0002118	98.03	gold quality
left ovary	UBERON:0002119	97.97	gold quality
testis	UBERON:0000473	97.96	gold quality
right uterine tube	UBERON:0001302	97.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.74	gold quality
body of uterus	UBERON:0009853	97.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.68	gold quality
colonic epithelium	UBERON:0000397	97.67	gold quality
corpus callosum	UBERON:0002336	97.64	gold quality
lymph node	UBERON:0000029	97.48	gold quality
endocervix	UBERON:0000458	97.44	gold quality
spleen	UBERON:0002106	97.37	gold quality
left uterine tube	UBERON:0001303	97.34	gold quality
ectocervix	UBERON:0012249	97.29	gold quality
ovary	UBERON:0000992	97.24	gold quality
rectum	UBERON:0001052	97.21	gold quality
spinal cord	UBERON:0002240	97.18	gold quality
vermiform appendix	UBERON:0001154	97.15	gold quality
tibial nerve	UBERON:0001323	97.13	gold quality
peritoneum	UBERON:0002358	97.07	gold quality
omental fat pad	UBERON:0010414	97.07	gold quality
calcaneal tendon	UBERON:0003701	97.06	gold quality
caecum	UBERON:0001153	96.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.93	gold quality
endometrium	UBERON:0001295	96.89	gold quality
mucosa of stomach	UBERON:0001199	96.81	gold quality
cerebellar hemisphere	UBERON:0002245	96.81	gold quality
thymus	UBERON:0002370	96.80	gold quality
cerebellar cortex	UBERON:0002129	96.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.72	gold quality
tendon of biceps brachii	UBERON:0008188	96.71	gold quality
mucosa of transverse colon	UBERON:0004991	96.70	gold quality
smooth muscle tissue	UBERON:0001135	96.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.67	gold quality
left lobe of thyroid gland	UBERON:0001120	96.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.62	gold quality
adenohypophysis	UBERON:0002196	96.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.58	gold quality
right lung	UBERON:0002167	96.50	gold quality
right lobe of thyroid gland	UBERON:0001119	96.49	gold quality
tonsil	UBERON:0002372	96.47	gold quality
middle frontal gyrus	UBERON:0002702	96.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.43	gold quality
lower esophagus mucosa	UBERON:0035834	96.42	gold quality
lower esophagus	UBERON:0013473	96.41	gold quality
metanephros cortex	UBERON:0010533	96.40	gold quality
minor salivary gland	UBERON:0001830	96.37	gold quality
upper lobe of left lung	UBERON:0008952	96.35	gold quality
uterus	UBERON:0000995	96.34	gold quality
thyroid gland	UBERON:0002046	96.31	gold quality
right atrium auricular region	UBERON:0006631	96.28	gold quality
bone marrow	UBERON:0002371	96.23	gold quality
vagina	UBERON:0000996	96.21	gold quality
descending thoracic aorta	UBERON:0002345	96.19	gold quality
cerebellum	UBERON:0002037	96.12	gold quality
esophagus	UBERON:0001043	96.10	gold quality
upper lobe of lung	UBERON:0008948	96.10	gold quality
transverse colon	UBERON:0001157	96.07	gold quality
female reproductive system	UBERON:0000474	96.04	gold quality
tendon	UBERON:0000043	96.00	gold quality
amygdala	UBERON:0001876	96.00	gold quality
small intestine	UBERON:0002108	95.95	gold quality
skin of abdomen	UBERON:0001416	95.93	gold quality
inferior vagus X ganglion	UBERON:0005363	95.90	gold quality
bone marrow cell	CL:0002092	95.89	gold quality
body of stomach	UBERON:0001161	95.89	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.87	gold quality
esophagus mucosa	UBERON:0002469	95.84	gold quality
gall bladder	UBERON:0002110	95.83	gold quality
pituitary gland	UBERON:0000007	95.80	gold quality
right frontal lobe	UBERON:0002810	95.76	gold quality
fundus of stomach	UBERON:0001160	95.66	gold quality
stomach	UBERON:0000945	95.59	gold quality
tibial artery	UBERON:0007610	95.59	gold quality
popliteal artery	UBERON:0002250	95.58	gold quality
myometrium	UBERON:0001296	95.57	gold quality
mouth mucosa	UBERON:0003729	95.56	gold quality
left coronary artery	UBERON:0001626	95.52	gold quality
intestine	UBERON:0000160	95.47	gold quality
sigmoid colon	UBERON:0001159	95.46	gold quality
aorta	UBERON:0000947	95.44	gold quality
body of pancreas	UBERON:0001150	95.43	gold quality
coronary artery	UBERON:0001621	95.43	gold quality
saliva-secreting gland	UBERON:0001044	95.35	gold quality
colon	UBERON:0001155	95.35	gold quality
apex of heart	UBERON:0002098	95.35	gold quality
right lobe of liver	UBERON:0001114	95.34	gold quality
large intestine	UBERON:0000059	95.30	gold quality
thoracic aorta	UBERON:0001515	95.27	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	957.81
E-HCAD-4	yes	42.05
E-HCAD-5	yes	40.72
E-CURD-112	yes	39.59
E-HCAD-10	yes	34.43
E-CURD-122	yes	22.58
E-GEOD-125970	yes	21.21
E-HCAD-1	yes	17.90
E-MTAB-6678	yes	7.88
E-MTAB-10553	yes	7.81
E-MTAB-9801	yes	5.82
E-GEOD-75140	no	1970.93
E-MTAB-11121	no	864.30
E-MTAB-7008	no	807.80
E-MTAB-10137	no	6.75

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	155.7	medium
Thymus	tissue	93.9
Tonsil	tissue	91.4	high
Lymph node	tissue	85.5	medium
Testis	tissue	75.6	high
Placenta	tissue	58.2	medium
Vagina	tissue	54.3	medium
Appendix	tissue	52.7	high
Rectum	tissue	48.3	high
Ovary	tissue	45.5	low
Colon	tissue	45.3	high
Spleen	tissue	43.6	low
Endometrium 1	tissue	43.5	medium
Liver	tissue	42.9	low
Smooth muscle	tissue	42.2	low
Adipose tissue	tissue	41.1	not detected
Seminal vesicle	tissue	40.9	medium
Pituitary gland	tissue	40.3
Parathyroid gland	tissue	38.6	medium
Cervix	tissue	37.8	medium
Small intestine	tissue	37.4	high
Fallopian tube	tissue	37.1	high
Breast	tissue	35.7	low
Retina	tissue	35.5
Urinary bladder	tissue	35.3	medium
Lung	tissue	33.7	high
Duodenum	tissue	32.6	high
Skin 1	tissue	31.3	high
Adrenal gland	tissue	29.9	low
Prostate	tissue	29.3	low
Stomach 1	tissue	28.4	medium
Epididymis	tissue	28.3	low
Salivary gland	tissue	27.8	low
Kidney	tissue	25.9	low
Heart muscle	tissue	25.6	low
Esophagus	tissue	25.6	high
Gallbladder	tissue	25.0	low
Thyroid gland	tissue	24.2	low
Cerebellum	tissue	23.1	low
Choroid plexus	tissue	21.4
Pancreas	tissue	21.3	low
Tongue	tissue	20.8
Skeletal muscle	tissue	20.3	low
Postcentral gyrus	tissue	18.9
Corpus callosum	tissue	17.4
Hippocampus	tissue	17.0	low
Locus coeruleus	tissue	16.9
Olfactory bulb	tissue	16.9
Hippocampal formation	tissue	14.6
Nucleus accumbens	tissue	14.4
Spinal cord	tissue	14.4
Amygdala	tissue	14.3
Prefrontal cortex	tissue	13.8
Cerebral cortex	tissue	13.8	low
Entorhinal cortex	tissue	13.8
Somatosensory cortex	tissue	13.7
Midbrain	tissue	13.6
Occipital cortex	tissue	13.6
Hypothalamus	tissue	13.5
Substantia nigra	tissue	13.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (47.9), Paraventricular nucleus (43.7), Nucleus gracilis (38.1), Temporal white matter (37.5), Area striata (white matter) (36.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, SP1

miRNA regulators (miRDB)

Targeting NASP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 55 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-1284	99.67	73.56	1353

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.394, missense Z 0.926 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000350030 splits into 5 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:45,584,147–45,602,340	89 / 79.2	1.12	no
1:45,602,341–45,606,482	17 / 38.6	0.44	no
1:45,606,483–45,614,109	464 / 469.4	0.99	no
1:45,614,110–45,615,165	60 / 114.6	0.52	no
1:45,615,166–45,618,138	218 / 219.6	0.99	no
DepMap (CRISPR cell-line fitness): dependent in 40.6% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): HPAF-II (-1.412), KP-N-YN (-1.409), NCI-H2126 (-1.114), Evsa-T (-1.094), CHP-212 (-1.075), NCI-H226 (-1.071), NCI-H460 (-1.011), SF126 (-0.991), TYK-nu (-0.99), LS513 (-0.982), KE-97 (-0.981), S-117 (-0.967), PA-TU-8988S (-0.959), HARA (-0.956), HCC515 (-0.949).

Literature-anchored findings (GeneRIF, showing 22)

• NASP and the linker histones are key players in the assembly of chromatin after DNA replication (PMID:16728391)
• NASP forms distinct, high specificity complexes with histones H3 and H4. (PMID:18782834)
• NASP belongs to a network of genes and gene functions that are critical for cell survival (PMID:19439102)
• NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed (PMID:20164540)
• A deletion analysis of sNASP revealed that the central region, amino acid residues 26-325, of sNASP is responsible for nucleosome assembly in vitro. (PMID:20167597)
• tNASP is critical for the survival of prostate cancer cells; targeting tNASP expression can lead to a new approach for prostate cancer treatment. (PMID:21496299)
• sNASP interacts with linker and core histones through distinct structural domains. (PMID:21965532)
• an increase of miR-29a, and hence decrease of Nasp, may contribute to inhibit cell proliferation during postnatal organ development. (PMID:22194605)
• The insights into NASP function and the existence of a tunable reservoir in mammalian cells demonstrate that contingency is integrated into the histone supply chain to respond to unexpected changes in demand. (PMID:22195965)
• Studies indicate that histone chalerones nucleoplasmin (NPM2/NPM3) preferentially associated with histones H2A-H2B in the egg and the nuclear autoantigenic sperm protein (NASP) families. (PMID:22968912)
• NASP family Proteins are highly conserved throughout the eukaryotes and posses four TPR motifs. It was likely present in the last common ancestor of eukaryotes possibly representing an important innovation regarding H3/H4 transport mechanism. Different TPR motifs in NASP have evolved at different rates with TPR1/4 evolving faster than TPR2/3. (PMID:24951090)
• These results provide evidence that tNASP is ubiquitously produced in various types of human tissues and promotes in vitro nucleosome assembly with H3 variant specificity. (PMID:25615412)
• Our research demonstrates that knockdown of tNASP effectively inhibits the proliferation and causes G1 phase arrest through ERK/MAPK signal pathway. (PMID:25669170)
• findings reveal a new mode of interaction between a TPR repeat domain of histone chaperone sNASP and an evolutionarily conserved peptide motif found in canonical H3 and in all histone H3 variants (PMID:26673727)
• NASP is targeted by miR-29c in gastric cancer cells. miR-29c can decrease NASP expression and the effects observed following miR-29c overexpression are partially due to NASP depletion. (PMID:28173777)
• Results found that NASP expression levels were upregulated in liver tumors. Its down-regulation inhibited liver cells from forming tumors. Also, NASP depletion led to a global decrease of histone H3K9me1 modification associated with newly H3 processing, which occurred directly at the promoters of up-regulated anti-tumor genes BACH2 and RunX1T1. (PMID:30076957)
• miR-381-3p targeted and suppressed NASP gene, reduced the viability, migration, invasion, EMT of HNSCC cells, demonstrating that miR-381-3p has the potential to be a therapeutic target in inhibiting the progression of HNSCC (PMID:31797734)
• Knockdown of long noncoding RNA colorectal neoplasia differentially expressed inhibits hepatocellular carcinoma progression by mediating the expression of nuclear autoantigenic sperm protein. (PMID:34633056)
• UBR7 acts as a histone chaperone for post-nucleosomal histone H3. (PMID:34786730)
• Home Dust Mites Promote MUC5AC Hyper-Expression by Modulating the sNASP/TRAF6 Axis in the Airway Epithelium. (PMID:36012669)
• NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways. (PMID:38443156)
• Nuclear autoantigenic sperm protein facilitates glioblastoma progression and radioresistance by regulating the ANXA2/STAT3 axis. (PMID:38605477)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nasp	ENSDARG00000039208
mus_musculus	Nasp	ENSMUSG00000028693
rattus_norvegicus	Nasp	ENSRNOG00000016454
drosophila_melanogaster	Nasp	FBGN0037624
caenorhabditis_elegans		WBGENE00007500

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1355328) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased embryo size	1
embryonic growth arrest	1
embryonic lethality before implantation, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q2T9P4	84.7%	Diamond
Oryctolagus cuniculus	P27123	80.2%	Diamond
Xenopus laevis	P06180	60.9%	Diamond
Halocynthia roretzi	Q02508	43.2%	Diamond
Schizosaccharomyces pombe 972h-	Q9USQ4	32.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
AKR1A1	protein-coding	10327
CCDC163	protein-coding	126661
MMACHC	protein-coding	25974
PRDX1	protein-coding	5052
CCDC17	protein-coding	149483
GPBP1L1	protein-coding	60313
IPP	protein-coding	3652
TMEM69	protein-coding	51249

Protein

Protein identifiers

Nuclear autoantigenic sperm protein — P49321 (reviewed: P49321)

All UniProt accessions (14): E9PAU3, E9PI86, E9PJQ2, E9PKR5, E9PNB5, E9PPQ8, E9PPR5, E9PQG5, E9PRH9, P49321, H0YDS9, H0YF33, Q5T624, Q5T626

UniProt curated annotations — full annotation on UniProt →

Function. Component of the histone chaperone network. Binds and stabilizes histone H3-H4 not bound to chromatin to maintain a soluble reservoir and modulate degradation by chaperone-mediated autophagy. Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. Stabilizes soluble histone H3-H4. Stabilizes soluble histone H3-H4.

Subunit / interactions. Binds to linker H1 histones. Interacts with histones H2A, H2B, H3 and H4. Interacts with histone H3.3. Interacts with histones H3 and H4; NASP is a histone chaperone that stabilizes and maintains a soluble pool of histone H3-H4 dimers. Interacts with ASF1A and ASF1B; the interaction is probably indirect and mediated by H3-H4. Also binds to HSP90 in the cytoplasm; this interaction stimulates binding of NASP to H1-6/H1T.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Isoform 1 is testis- and sperm-specific.

Similarity. Belongs to the NASP family.

Isoforms (4)

UniProt ID	Names	Canonical?
P49321-1	1, Testicular NASP, tNASP	yes
P49321-2	2, Somatic NASP, sNASP
P49321-3	3
P49321-4	4

RefSeq proteins (3): NP_001182122, NP_002473, NP_689511 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019544	Tetratricopeptide_SHNi-TPR_dom	Domain
IPR019734	TPR_rpt	Repeat
IPR051730	NASP-like	Family

Pfam: PF10516, PF13181

UniProt features (73 total): modified residue 34, compositionally biased region 7, sequence conflict 7, helix 7, region of interest 6, repeat 3, splice variant 3, initiator methionine 1, chain 1, coiled-coil region 1, short sequence motif 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
7V1M	Structural basis for the co-chaperone relationship of sNASP and ASF1b	X-RAY DIFFRACTION	2.83
7V1L	Structure of sNASP core in complex with H3 alpha3 helix peptide	X-RAY DIFFRACTION	2.85
7V6P	Crystal structure of human sNASP TPR domain	X-RAY DIFFRACTION	2.9
7V6Q	Crystal structure of sNASP-ASF1A-H3.1-H4 complex	X-RAY DIFFRACTION	3
7V1K	Apo structure of sNASP core	X-RAY DIFFRACTION	3.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49321-F1	58.07	0.27

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF enhanced

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 (35)

Type	Positions
N-acetylalanine	2
N6-acetyllysine	33, 243, 288
Phosphothreonine	123, 170, 390, 464, 477, 490, 683, 138
Phosphoserine	127, 176, 189, 191, 244, 299, 321, 397, 408, 421, 451, 480, 497, 503, 662, 705, 706, 726, 745, 751, 756, 141
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	736

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 371 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, E2F_Q4_01, GNF2_MSH2, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_SMC1L1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, BROWNE_HCMV_INFECTION_8HR_UP, FISCHER_G1_S_CELL_CYCLE, CROONQUIST_NRAS_SIGNALING_DN, GCM_NPM1

GO Biological Process (8): blastocyst development (GO:0001824), DNA replication (GO:0006260), nucleosome assembly (GO:0006334), DNA replication-dependent chromatin assembly (GO:0006335), male gonad development (GO:0008584), protein transport (GO:0015031), response to testosterone (GO:0033574), CENP-A containing chromatin assembly (GO:0034080)

GO Molecular Function (3): histone binding (GO:0042393), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

GO top-level categories

24 GO namespaces:

Category	Terms
chromatin organization	3
cellular anatomical structure	3
binding	2
in utero embryonic development	1
animal gross anatomical part developmental process	1
DNA metabolic process	1
DNA biosynthetic process	1
nucleosome organization	1
protein-DNA complex assembly	1
gonad development	1
development of primary male sexual characteristics	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
response to lipid	1
response to ketone	1
kinetochore assembly	1
protein localization to CENP-A containing chromatin	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
nucleosome assembly	BP	direct assay
chromatin	CC	direct assay
nucleoplasm	CC	direct assay
protein-containing complex	CC	direct assay
histone binding	MF	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,932 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NASP	SLBP	Q14493	911
NASP	H1-6	P22492	798
NASP	MYCBP2	O75592	759
NASP	IPO4	Q8TEX9	638
NASP	HAT1	O14929	625
NASP	ASF1A	Q9Y294	610
NASP	ASF1B	Q9NVP2	609
NASP	UBR7	Q8N806	591
NASP	RBBP7	Q16576	556
NASP	CHAF1B	Q13112	554
NASP	RCC1	P18754	549
NASP	GAS2L3	Q86XJ1	535
NASP	MCM4	P33991	526
NASP	GINS2	Q9Y248	525
NASP	WDR76	Q9H967	523

IntAct

Human interaction partners of NASP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
H3C1	physical association	0.910	3
H4C16	association	0.530	1
HAT1	association	0.530	1
TERF2IP	physical association	0.510	2
FXR2	physical association	0.370	1
H3-5	physical association	0.370	1
H3C13	physical association	0.370	1
HDAC6	physical association	0.370	1
PTK2	physical association	0.370	1
TERF2	physical association	0.370	1
DONSON	association	0.350	1
ARF6	physical association	0.000	1
BCAR3	physical association	0.000	1
FTSJ1	physical association	0.000	1
GABARAPL2	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1
ITSN1	physical association	0.000	1
LUC7L2	physical association	0.000	1
MCC	physical association	0.000	1
MTNR1A	physical association	0.000	1
SGK1	physical association	0.000	1
STXBP1	physical association	0.000	1
TFE3	physical association	0.000	1
TIAM1	physical association	0.000	1
TRAF6	physical association	0.000	1
ULK2	physical association	0.000	1

BioGRID (317 interactions; top human partners by supporting records): HIST1H3A (Proximity Label-MS; 13 records), ASF1A (Affinity Capture-MS; 10 records), H3F3A (Co-fractionation; 7 records), HIST1H3E (Co-purification; 6 records), ASF1B (Affinity Capture-MS; 5 records), HIST1H4A (Affinity Capture-MS; 5 records), RBBP4 (Affinity Capture-MS; 5 records), H3F3B (Two-hybrid; 4 records), HAT1 (Affinity Capture-MS; 4 records), HIST1H3H (Two-hybrid; 4 records), AIMP1 (Cross-Linking-MS (XL-MS); 3 records), HIST1H3C (Two-hybrid; 3 records), HIST1H3F (Two-hybrid; 3 records), HIST1H3G (Two-hybrid; 3 records), HIST2H3A (Affinity Capture-MS; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
CSNK2A1	“down-regulates activity”	NASP	phosphorylation
NASP	“down-regulates activity”	TRAF6	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
Histone H3.1 complex	10	CHAF1B, IPO4, ASF1A, ASF1B, CHAF1A, H3C1, H4C1, HAT1, NASP, RBBP4
Histone H3.3 complex	9	ASF1A, HIRA, IPO4, NASP, ASF1B, H3-3A, H4C1, HAT1, RBBP4
ASF1-histone containing complex	7	ASF1A, ASF1B, CHAF1B, CHEK2, H3C1, NASP, ST13

Disease & clinical

Genetic variants

Variant evidence for NASP: 130 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	12
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 1,305):

Position(s)	Effect	Δscore	Sites
1:45591271–45591272	donor_loss	1.0000	5
1:45602366–45602367	donor_loss	1.0000	5
1:45604934–45604935	acceptor_loss	1.0000	4
1:45605017–45605018	donor_loss	1.0000	5
1:45606480	acceptor_loss	1.0000	2
1:45613167	acceptor_loss	1.0000	3
1:45613249–45613250	donor_loss	1.0000	5
1:45614082	acceptor_gain	1.0000
1:45615007	acceptor_gain	1.0000
1:45615011–45615012	acceptor_loss	1.0000	5

AlphaMissense

1,067 missense substitutions predicted likely pathogenic (of 5,148 scored), across 244 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D655	8	0.968	0.994
F66	8	0.956	0.996
M521	8	0.933	0.988
H714	8	0.883	0.965
D523	8	0.859	0.976
N557	8	0.838	0.971
W519	7	0.998	1.000
E554	7	0.988	0.996
E102	7	0.985	0.998
F529	7	0.982	0.992
F565	7	0.982	0.997
F607	7	0.979	0.996
C84	7	0.972	0.998
E550	7	0.971	0.984
F88	7	0.966	0.990
E97	7	0.965	0.994
D711	7	0.962	0.978
F89	7	0.955	0.989
C568	7	0.950	0.999
R720	7	0.937	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Testicular Germ Cell Tumor)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.02e-07

Disease associations

OMIM: gene MIM:603185 | disease phenotypes:

GWAS associations

12 associations:

Study	Trait	p-value
GCST010083_244	Hemoglobin levels	6e-24
GCST004604_13	Hematocrit	3e-14
GCST010702_139	Subcortical volume (MOSTest)	4e-14
GCST010703_210	Brain morphology (MOSTest)	2e-13
GCST004615_48	Hemoglobin concentration	3e-13
GCST010700_23	Cortical thickness (MOSTest)	1e-10
GCST005951_47	Body mass index	8e-10
GCST010697_3	Cortical surface area (min-P)	2e-8
GCST010701_128	Cortical surface area (MOSTest)	2e-8
GCST010696_21	Cortical thickness (min-P)	3e-8
GCST010698_61	Subcortical volume (min-P)	3e-8
GCST010699_25	Brain morphology (min-P)	3e-8

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724618 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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
7.09	Kd	81.49	nM	CHEMBL5653589
7.09	ED50	81.49	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148825: Binding affinity to human NASP incubated for 45 mins by Kinobead based pull down assay	kd	0.0815	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects expression	4
methylmercuric chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression, increases stability	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
geraniol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
triadimefon	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651867	Binding	Binding affinity to human NASP 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*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3BV	Abcam HEK293T NASP KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NASP across ~30M SureChEMBL compounds — explore on Sugi Predict.