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): 129 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 40.6% of screened cell lines
• MANE Select transcript: NM_002482

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: 52 — 39 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

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

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.

FANTOM5 promoters (2 alternative TSS)

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

Top tissues by expression

295 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, SP1

miRNA regulators (miRDB)

55 targeting NASP, 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-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

DepMap (CRISPR cell-line fitness): dependent in 40.6% of screened cell lines.

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

Protein

Protein identifiers

Nuclear autoantigenic sperm protein — P49321 (reviewed: P49321)

All UniProt accessions (14): P49321, E9PAU3, E9PI86, E9PJQ2, E9PKR5, E9PNB5, E9PPQ8, E9PPR5, E9PQG5, E9PRH9, 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.

PDB	Method	Resolution (Å)
7V1M	X-RAY DIFFRACTION	2.83
7V1L	X-RAY DIFFRACTION	2.85
7V6P	X-RAY DIFFRACTION	2.9
7V6Q	X-RAY DIFFRACTION	3
7V1K	X-RAY DIFFRACTION	3.29

Predicted structure (AlphaFold)

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

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): 2, 33, 123, 127, 170, 176, 189, 191, 243, 244, 288, 299, 321, 390, 397, 408, 421, 451, 464, 477 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

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

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	3
cellular anatomical structure	3
binding	2
in utero embryonic development	1
anatomical structure development	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

Protein interactions and networks

STRING

2551 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NASP	SLBP	Q14493	911
NASP	H1-0	P07305	853
NASP	ASF1B	Q9NVP2	842
NASP	ASF1A	Q9Y294	833
NASP	HSP90AA1	P07900	809
NASP	HSP90AB1	P08238	808
NASP	H1-6	P22492	791
NASP	IPO4	Q8TEX9	771
NASP	HAT1	O14929	768
NASP	MYCBP2	O75592	767
NASP	H4C7	Q99525	761
NASP	H4C16	P02304	760
NASP	RBBP7	Q16576	753
NASP	RBBP4	P31149	689
NASP	NPM1	P06748	643

IntAct

103 interactions, top by confidence:

A	B	Type	Score
NASP	H3C1	psi-mi:“MI:0915”(physical association)	0.910
NASP	H3C1	psi-mi:“MI:0914”(association)	0.910
H3C1	HAT1	psi-mi:“MI:0914”(association)	0.770
H4C16	HAT1	psi-mi:“MI:0914”(association)	0.700
ASF1A	HAT1	psi-mi:“MI:0914”(association)	0.640
ASF1B	HAT1	psi-mi:“MI:0914”(association)	0.640
NASP	HAT1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
ASF1A	MCM4	psi-mi:“MI:0914”(association)	0.530
NASP	H4C16	psi-mi:“MI:0914”(association)	0.530
TERF2IP	NASP	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
NASP	TERF2	psi-mi:“MI:0915”(physical association)	0.370
NASP	H3-5	psi-mi:“MI:0915”(physical association)	0.370
NASP	FXR2	psi-mi:“MI:0915”(physical association)	0.370
NASP	HDAC6	psi-mi:“MI:0915”(physical association)	0.370
PTK2	NASP	psi-mi:“MI:0915”(physical association)	0.370
NASP	H3C13	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
NASP	DONSON	psi-mi:“MI:0914”(association)	0.350
POLR2G	POLR2B	psi-mi:“MI:0914”(association)	0.350
ASF1A	CDAN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (314): NASP (Affinity Capture-MS), NASP (Two-hybrid), HIST1H3H (Two-hybrid), H3F3C (Two-hybrid), HIST1H3G (Two-hybrid), HIST2H3C (Two-hybrid), HIST1H3H (Two-hybrid), DKC1 (Co-fractionation), NASP (Co-fractionation), NASP (Affinity Capture-MS), NASP (Proximity Label-MS), NASP (Co-purification), NASP (Affinity Capture-MS), NASP (Affinity Capture-MS), NASP (Affinity Capture-MS)

ESM2 similar proteins: A0A3L6DPG1, A1C4X0, A1CZU9, A2QUR1, A4R6K8, A6QT51, A6S3N2, B0WQG0, O03982, O24591, O80358, O82089, P06180, P07936, P08199, P09405, P13383, P14649, P15308, P19338, P31230, P49321, P92985, Q0CE43, Q0JL44, Q1DSY1, Q2GLX8, Q2UA18, Q4R4J7, Q4WEP0, Q56WK6, Q56ZI2, Q5ATZ7, Q5RF26, Q6PD99, Q8CI43, Q8JFV8, Q8RWG8, Q90679, Q94C59

Diamond homologs: P06180, P27123, P49321, Q02508, Q2T9P4, Q66HD3, Q99MD9, Q9I7K6, Q9USQ4

SIGNOR signaling

2 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Dengue Virus-Host Interactions	10	6.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	8	11.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2564 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45584201:GACAA:G	donor_gain	1.0000
1:45584206:G:GG	donor_gain	1.0000
1:45591221:AGA:A	acceptor_loss	1.0000
1:45591222:GA:G	acceptor_gain	1.0000
1:45591268:GAG:G	donor_gain	1.0000
1:45591271:G:GA	donor_loss	1.0000
1:45602253:A:AG	acceptor_gain	1.0000
1:45602253:AGTCT:A	acceptor_gain	1.0000
1:45602254:G:GA	acceptor_gain	1.0000
1:45602254:GT:G	acceptor_gain	1.0000
1:45602254:GTCTG:G	acceptor_gain	1.0000
1:45602349:G:GT	donor_gain	1.0000
1:45602361:CTTTT:C	donor_gain	1.0000
1:45602362:TTTT:T	donor_gain	1.0000
1:45602363:TTT:T	donor_gain	1.0000
1:45602364:TT:T	donor_gain	1.0000
1:45602365:TGT:T	donor_loss	1.0000
1:45602366:G:C	donor_loss	1.0000
1:45602366:G:GG	donor_gain	1.0000
1:45602367:TAAG:T	donor_loss	1.0000
1:45602368:AAG:A	donor_loss	1.0000
1:45604931:TGTA:T	acceptor_loss	1.0000
1:45604933:TA:T	acceptor_loss	1.0000
1:45604934:A:AG	acceptor_gain	1.0000
1:45604934:AGAG:A	acceptor_gain	1.0000
1:45604935:G:GT	acceptor_gain	1.0000
1:45604935:GA:G	acceptor_gain	1.0000
1:45604935:GAGG:G	acceptor_gain	1.0000
1:45605013:CAAGG:C	donor_loss	1.0000
1:45605014:AAG:A	donor_loss	1.0000

AlphaMissense

5148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45602352:G:C	A69P	1.000
1:45604991:G:A	G92R	1.000
1:45604991:G:C	G92R	1.000
1:45604991:G:T	G92W	1.000
1:45604992:G:A	G92E	1.000
1:45605001:T:C	L95P	1.000
1:45605004:T:C	L96P	1.000
1:45614139:T:C	L517P	1.000
1:45614144:T:A	W519R	1.000
1:45614144:T:C	W519R	1.000
1:45614146:G:C	W519C	1.000
1:45614146:G:T	W519C	1.000
1:45614154:T:C	L522P	1.000
1:45614337:T:C	L546P	1.000
1:45614343:T:C	L548P	1.000
1:45614346:G:A	G549E	1.000
1:45614352:T:A	V551D	1.000
1:45615115:T:C	L590P	1.000
1:45602295:G:A	G50R	0.999
1:45602295:G:C	G50R	0.999
1:45602296:G:A	G50E	0.999
1:45602308:T:C	L54P	0.999
1:45602331:G:C	A62P	0.999
1:45602332:C:A	A62D	0.999
1:45602335:T:A	V63D	0.999
1:45602355:G:C	A70P	0.999
1:45604992:G:T	G92V	0.999
1:45605001:T:A	L95H	0.999
1:45605012:G:C	A99P	0.999
1:45606499:T:C	L106S	0.999

dbSNP variants (sampled 300 via entrez): RS1000022778 (1:45586945 A>C,T), RS1000116321 (1:45608800 T>C), RS1000133554 (1:45613851 T>A,C), RS1000238209 (1:45589581 A>C), RS1000239774 (1:45601711 T>C), RS1000253985 (1:45608434 G>A,T), RS1000346919 (1:45595002 TC>T,TCC), RS1000454906 (1:45610185 C>T), RS1000588425 (1:45609927 G>A), RS1000705774 (1:45597159 T>C,G), RS1000778460 (1:45603543 T>C), RS1000841168 (1:45601914 G>A), RS1000891387 (1:45591786 C>A), RS1000947219 (1:45597410 A>G), RS1000976933 (1:45605468 GTTTT>G,GT,GTT,GTTT,GTTTTT,GTTTTTT)

Disease associations

OMIM: gene MIM:603185 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004604_13	Hematocrit	3.000000e-14
GCST004615_79	Hemoglobin concentration	3.000000e-13
GCST005951_37	Body mass index	8.000000e-10
GCST010083_341	Hemoglobin levels	6.000000e-24
GCST010696_7	Cortical thickness (min-P)	3.000000e-08
GCST010697_28	Cortical surface area (min-P)	2.000000e-08
GCST010698_30	Subcortical volume (min-P)	3.000000e-08
GCST010699_45	Brain morphology (min-P)	3.000000e-08
GCST010700_23	Cortical thickness (MOSTest)	1.000000e-10
GCST010701_9	Cortical surface area (MOSTest)	2.000000e-08
GCST010702_139	Subcortical volume (MOSTest)	4.000000e-14
GCST010703_258	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (5, from GWAS)

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 (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
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	affects expression, decreases 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	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tretinoin	decreases expression	2
Valproic Acid	increases methylation, decreases expression, increases expression	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	increases abundance, affects cotreatment, increases oxidation	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)

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