NPAS1

Summary

NPAS1 (neuronal PAS domain protein 1, HGNC:7894) is a protein-coding gene on chromosome 19q13.32, encoding Neuronal PAS domain-containing protein 1 (Q99742). May control regulatory pathways relevant to schizophrenia and to psychotic illness.

The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. Studies of a related mouse gene suggest that it functions in neurons. The exact function of this gene is unclear, but it may play protective or modulatory roles during late embryogenesis and postnatal development.

Source: NCBI Gene 4861 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 87 total
• GTEx eGene: eQTL in 12 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_002517
• Notable: 87 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7894
Approved symbol	NPAS1
Name	neuronal PAS domain protein 1
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	MOP5, PASD5, bHLHe11
Ensembl gene	ENSG00000130751
Ensembl biotype	protein_coding
OMIM	603346
Entrez	4861

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000602212

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

ENST00000602212, ENST00000439365, ENST00000449844, ENST00000594257, ENST00000594670, ENST00000600352, ENST00000601169, ENST00000602189, ENST00000906440, ENST00000906441, ENST00000940003, ENST00000941427, ENST00000941428, ENST00000984110, ENST00000984111, ENST00001020128, ENST00001020129, ENST00001020130, ENST00001088556, ENST00001088557, ENST00001088558, ENST00001127850, ENST00001135037

RefSeq mRNA: 2 — MANE Select: NM_002517 NM_001321086, NM_002517

CCDS: CCDS12694, CCDS82371

Canonical transcript exons

ENST00000602212 — 12 exons

Exon	Start	End
ENSE00000895953	47039036	47039151
ENSE00002237784	47021612	47021847
ENSE00003033461	47019837	47019997
ENSE00003192883	47045191	47045775
ENSE00003201377	47021006	47021169
ENSE00003463399	47040978	47041125
ENSE00003471055	47032278	47032351
ENSE00003497051	47042810	47042904
ENSE00003512242	47039407	47039564
ENSE00003541771	47035964	47036129
ENSE00003603750	47032643	47032732
ENSE00003643430	47040444	47040550

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 85.96.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8455 / max 94.0971, expressed in 798 samples.

Highest expression (Bgee): buccal mucosa cell, frontal lobe, prefrontal cortex, cingulate cortex, anterior cingulate cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NPAS1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	7.5e-20	-0.34	19:47009977:G:A
Nerve Tibial	eqtl	1.2e-06	-0.57	19:47020636:C:A
Artery Tibial	eqtl	1.3e-05	-0.55	19:47021137:C:G
Skin Sun Exposed Lower leg	eqtl	1.3e-05	+0.44	19:47021349:A:C
Thyroid	eqtl	2.6e-04	-0.53	19:47009977:G:A
Artery Aorta	eqtl	8.9e-04	-0.73	19:47021137:C:G
Adipose Subcutaneous	eqtl	9.6e-04	-0.21	19:46994621:A:G
Heart Atrial Appendage	sqtl	3.1e-03	+1.90	19:46254232:A:C
Adipose Visceral Omentum	eqtl	3.8e-03	-0.14	19:47053840:C:G
Whole Blood	eqtl	2.0e-02	-0.19	19:47078207:A:C
Brain Frontal Cortex BA9	eqtl	2.7e-02	+0.17	19:47033003:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.1e-02	-0.10	19:47011365:T:C
Esophagus Mucosa	eqtl	4.0e-02	+0.46	19:46373607:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
176623	1.9994	552
176624	0.7387	338
176622	0.1074	43

Top tissues by expression

showing 100 of 270 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	85.96	silver quality
right frontal lobe	UBERON:0002810	81.20	gold quality
prefrontal cortex	UBERON:0000451	80.86	gold quality
cingulate cortex	UBERON:0003027	79.72	gold quality
anterior cingulate cortex	UBERON:0009835	79.53	gold quality
tendon of biceps brachii	UBERON:0008188	79.01	silver quality
amygdala	UBERON:0001876	77.89	gold quality
frontal cortex	UBERON:0001870	77.35	gold quality
neocortex	UBERON:0001950	77.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.44	gold quality
skin of leg	UBERON:0001511	76.39	gold quality
pancreatic ductal cell	CL:0002079	76.33	silver quality
triceps brachii	UBERON:0001509	76.27	gold quality
skin of abdomen	UBERON:0001416	75.98	gold quality
cerebral cortex	UBERON:0000956	75.19	gold quality
gluteal muscle	UBERON:0002000	75.11	gold quality
ganglionic eminence	UBERON:0004023	73.78	gold quality
zone of skin	UBERON:0000014	73.57	gold quality
Ammon’s horn	UBERON:0001954	73.14	gold quality
cortical plate	UBERON:0005343	72.85	gold quality
temporal lobe	UBERON:0001871	72.21	gold quality
lower esophagus mucosa	UBERON:0035834	71.83	gold quality
parotid gland	UBERON:0001831	71.70	gold quality
telencephalon	UBERON:0001893	71.67	gold quality
descending thoracic aorta	UBERON:0002345	71.16	gold quality
secondary oocyte	CL:0000655	71.14	gold quality
ventricular zone	UBERON:0003053	70.94	gold quality
forebrain	UBERON:0001890	70.67	gold quality
hypothalamus	UBERON:0001898	70.58	gold quality
oocyte	CL:0000023	70.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.04	gold quality
pigmented layer of retina	UBERON:0001782	69.93	gold quality
primary visual cortex	UBERON:0002436	69.12	gold quality
brain	UBERON:0000955	68.74	gold quality
biceps brachii	UBERON:0001507	68.74	gold quality
tongue squamous epithelium	UBERON:0006919	68.62	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	68.60	gold quality
inferior olivary complex	UBERON:0002127	68.56	gold quality
Brodmann (1909) area 10	UBERON:0013541	68.50	gold quality
central nervous system	UBERON:0001017	68.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	67.78	gold quality
thoracic aorta	UBERON:0001515	67.50	gold quality
embryo	UBERON:0000922	67.48	gold quality
ascending aorta	UBERON:0001496	67.42	gold quality
vena cava	UBERON:0004087	67.16	silver quality
right uterine tube	UBERON:0001302	66.66	gold quality
spleen	UBERON:0002106	66.65	gold quality
superior frontal gyrus	UBERON:0002661	66.42	gold quality
endometrium epithelium	UBERON:0004811	65.83	gold quality
gingival epithelium	UBERON:0001949	65.79	gold quality
occipital lobe	UBERON:0002021	65.68	gold quality
substantia nigra	UBERON:0002038	65.50	gold quality
postcentral gyrus	UBERON:0002581	65.27	silver quality
nucleus accumbens	UBERON:0001882	65.09	gold quality
entorhinal cortex	UBERON:0002728	65.05	silver quality
body of stomach	UBERON:0001161	64.99	gold quality
gingiva	UBERON:0001828	64.77	gold quality
midbrain	UBERON:0001891	64.51	gold quality
medial globus pallidus	UBERON:0002477	64.24	silver quality
caudate nucleus	UBERON:0001873	64.18	gold quality
parietal lobe	UBERON:0001872	64.01	silver quality
decidua	UBERON:0002450	63.86	silver quality
aorta	UBERON:0000947	63.56	gold quality
right coronary artery	UBERON:0001625	63.37	gold quality
mucosa of transverse colon	UBERON:0004991	63.32	gold quality
putamen	UBERON:0001874	63.25	gold quality
nasal cavity epithelium	UBERON:0005384	63.19	gold quality
globus pallidus	UBERON:0001875	62.56	silver quality
stromal cell of endometrium	CL:0002255	62.49	gold quality
esophagus mucosa	UBERON:0002469	62.43	gold quality
adenohypophysis	UBERON:0002196	62.16	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.06	gold quality
right atrium auricular region	UBERON:0006631	62.04	gold quality
pituitary gland	UBERON:0000007	61.86	gold quality
upper arm skin	UBERON:0004263	61.84	gold quality
frontal pole	UBERON:0002795	61.61	gold quality
stomach	UBERON:0000945	61.59	gold quality
middle frontal gyrus	UBERON:0002702	61.58	gold quality
quadriceps femoris	UBERON:0001377	61.52	gold quality
vastus lateralis	UBERON:0001379	61.39	gold quality
cardiac atrium	UBERON:0002081	61.38	gold quality
squamous epithelium	UBERON:0006914	61.29	gold quality
superficial temporal artery	UBERON:0001614	61.26	gold quality
paraflocculus	UBERON:0005351	61.16	gold quality
germinal epithelium of ovary	UBERON:0001304	61.15	gold quality
cerebellar vermis	UBERON:0004720	60.78	gold quality
cartilage tissue	UBERON:0002418	60.76	gold quality
popliteal artery	UBERON:0002250	60.65	gold quality
tibial artery	UBERON:0007610	60.63	gold quality
cortex of kidney	UBERON:0001225	60.46	gold quality
metanephros	UBERON:0000081	60.31	gold quality
esophagus squamous epithelium	UBERON:0006920	60.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.02	gold quality
middle temporal gyrus	UBERON:0002771	59.55	gold quality
renal glomerulus	UBERON:0000074	59.38	gold quality
corpus epididymis	UBERON:0004359	59.34	gold quality
kidney epithelium	UBERON:0004819	59.23	gold quality
tibia	UBERON:0000979	59.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.07

HPA expression

RNA tissue specificity: Tissue enhanced

59 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Locus coeruleus	tissue	10.9
Hippocampus	tissue	10.5
Postcentral gyrus	tissue	10.3
Choroid plexus	tissue	7.6
Frontal cortex	tissue	5.3
Hippocampal formation	tissue	4.3
Cerebral cortex	tissue	4.0
Motor cortex	tissue	4.0
Retrosplenial and cingulate cortex	tissue	3.7
Insular cortex	tissue	3.6
Skin 1	tissue	3.5
Prefrontal cortex	tissue	3.5
Pons	tissue	3.5
Retrosplenial cortex	tissue	3.4
Entorhinal cortex	tissue	3.1
Somatosensory cortex	tissue	3.0
Amygdala	tissue	2.8
Temporal cortex	tissue	2.6
Stomach 1	tissue	2.5
Occipital cortex	tissue	2.5
Putamen	tissue	2.4
Substantia nigra	tissue	2.4
Ventral forebrain	tissue	2.4
Periaqueductal gray	tissue	2.2
Nucleus accumbens	tissue	2.1
Caudate putamen	tissue	1.8
Basal ganglia	tissue	1.6
Spinal cord	tissue	1.5
Medulla oblongata	tissue	1.4
Pituitary gland	tissue	1.3
Hypothalamus	tissue	1.3
Spleen	tissue	1.2
Septum	tissue	1.2
Thalamus	tissue	1.1
Midbrain	tissue	1.0
Superior colliculi	tissue	0.8
Vagina	tissue	0.7
Retina	tissue	0.5
Corpus callosum	tissue	0.5
Lymph node	tissue	0.4
Cerebellum	tissue	0.4
Breast	tissue	0.3
Pancreas	tissue	0.3
Tonsil	tissue	0.3
Olfactory bulb	tissue	0.3
Appendix	tissue	0.3
Ovary	tissue	0.2
Lung	tissue	0.2
Kidney	tissue	0.2
Bone marrow	tissue	0.2
Fallopian tube	tissue	0.2
Testis	tissue	0.1
Esophagus	tissue	0.1
Salivary gland	tissue	0.1
Smooth muscle	tissue	0.1
Colon	tissue	0.1
Placenta	tissue	0.1
Liver	tissue	0.1
Thymus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Hippocampus, CA3 (14.6), Precentral gyrus (13.7), Piriform cortex (13.1), Paramedian reticular nucleus (12.4), Anterior cingulate cortex, supragenual-dorsal (11.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
ARNT	Repression
ARNT2	Repression
EPO	Unknown
TH	Repression

miRNA regulators (miRDB)

Targeting NPAS1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

2 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-324-3P	99.26	66.31	1034

Functional genomics

gnomAD constraint: pLI 4.09e-06, LOEUF 0.918, missense Z -1.4 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000602212 — one region, missense o/e 0.99.

Literature-anchored findings (GeneRIF, showing 2)

• Here the authors examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets. (PMID:27782878)
• Study provides a clear, unbiased view of the full spectrum of genes regulated by NPAS1 and NPAS3 and shows that these transcription factors are master regulators of neuropsychiatric function. These findings expose the molecular pathophysiology of NPAS1/3 mutations and provide a striking example of the shared, combinatorial nature of molecular pathways that underlie diagnostically distinct neuropsychiatric conditions. (PMID:28499489)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	npas1	ENSDARG00000015876
mus_musculus	Npas1	ENSMUSG00000001988
rattus_norvegicus	Npas1	ENSRNOG00000015376
drosophila_melanogaster	trh	FBGN0262139
caenorhabditis_elegans		WBGENE00001851

Paralogs (7): HIF1A (ENSG00000100644), SIM1 (ENSG00000112246), EPAS1 (ENSG00000116016), HIF3A (ENSG00000124440), NPAS3 (ENSG00000151322), SIM2 (ENSG00000159263), NPAS4 (ENSG00000174576)

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
Pan paniscus	A1YFY6	99.6%	Diamond
Pan troglodytes	A2T6X9	99.6%	Diamond
Bos grunniens	Q0PGG7	99.1%	Diamond
Bos taurus	Q9XTA5	99.1%	Diamond
Eospalax fontanierii baileyi	Q309Z6	88.1%	Diamond
Xenopus laevis	Q9W705	87.7%	Diamond
Xenopus tropicalis	B5DE09	87.6%	Diamond
Gallus gallus	Q9YIB9	78.9%	Diamond
Oncorhynchus mykiss	Q98SW2	55.2%	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
SAE1	protein-coding	10055
ZC3H4	protein-coding	23211
TMEM160	protein-coding	54958
SNAR-E	snRNA	100170220
ARHGAP35	protein-coding	2909
AP2S1	protein-coding	1175
MIR3191	ncRNA	100422832
MIR3190	ncRNA	100422899
BBC3	protein-coding	27113

Protein

Protein identifiers

Neuronal PAS domain-containing protein 1 — Q99742 (reviewed: Q99742)

Alternative names: Basic-helix-loop-helix-PAS protein MOP5, Class E basic helix-loop-helix protein 11, Member of PAS protein 5, PAS domain-containing protein 5

All UniProt accessions (4): Q99742, M0QX32, M0R1R8, M0R2M8

UniProt curated annotations — full annotation on UniProt →

Function. May control regulatory pathways relevant to schizophrenia and to psychotic illness. May play a role in late central nervous system development by modulating EPO expression in response to cellular oxygen level. Forms a heterodimer that binds core DNA sequence 5’-TACGTG-3’ within the hypoxia response element (HRE) leading to transcriptional repression on its target gene TH.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH-PAS protein. Interacts with ARNT; forms a heterodimer that binds core DNA sequence 5’-[AG]CGTG-3’ within the hypoxia response element (HRE) leading to a transcriptional repressor on its target gene TH.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99742-1	1	yes
Q99742-2	2

RefSeq proteins (2): NP_001308015, NP_002508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR011598	bHLH_dom	Domain
IPR013655	PAS_fold_3	Domain
IPR013767	PAS_fold	Domain
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00989, PF08447, PF23171

UniProt features (18 total): sequence conflict 5, domain 4, splice variant 3, compositionally biased region 3, region of interest 2, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99742-F1	67.23	0.44

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Basic domains, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IF approved

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: 106 (showing top): MODULE_52, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, MODULE_118, GOBP_STARTLE_RESPONSE, GOBP_PARENTAL_BEHAVIOR, GOBP_REPRODUCTIVE_BEHAVIOR, MODULE_123, MODULE_165, MODULE_497, MODULE_98, MODULE_18, GOBP_NEUROMUSCULAR_PROCESS, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY

GO Biological Process (5): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), central nervous system development (GO:0007417), negative regulation of DNA-templated transcription (GO:0045892), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

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

GO top-level categories

24 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	3
DNA-templated transcription	2
transcription cis-regulatory region binding	2
gene expression	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
nervous system development	1
system development	1
animal gross anatomical part developmental process	1
negative regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
protein binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

showing 15 of 778 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPAS1	LHX6	Q9UPM6	654
NPAS1	PER1	O15534	612
NPAS1	BHLHE41	Q9C0J9	548
NPAS1	PVALB	P20472	487
NPAS1	FOXP2	O15409	434
NPAS1	NPAS2	Q99743	405
NPAS1	RORB	Q92753	405
NPAS1	GBX1	Q14549	392
NPAS1	SPRY2	O43597	386
NPAS1	NKX2-1	P43699	385
NPAS1	ZSCAN30	Q86W11	377
NPAS1	GABRB1	P18505	370
NPAS1	RYR3	Q15413	370
NPAS1	NR1D2	Q14995	359
NPAS1	NXF3	Q9H4D5	359

IntAct

Human interaction partners of NPAS1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
DNAJB5	association	0.530	1
CIBAR1	association	0.350	1
DNAJB6	association	0.350	1
VWA8	association	0.350	1

BioGRID (257 interactions; top human partners by supporting records): AKAP1 (Affinity Capture-MS; 2 records), ARNT (Affinity Capture-MS; 2 records), ARNT2 (Affinity Capture-MS; 2 records), ATG2B (Affinity Capture-MS; 2 records), DNAJB5 (Affinity Capture-MS; 2 records), FAM83D (Affinity Capture-MS; 2 records), HAUS6 (Affinity Capture-MS; 2 records), HSPA8 (Affinity Capture-MS; 2 records), PPP6R1 (Affinity Capture-MS; 2 records), PRKACB (Affinity Capture-MS; 2 records), PRUNE (Affinity Capture-MS; 2 records), SMG7 (Affinity Capture-MS; 2 records), TUBB1 (Affinity Capture-MS; 2 records), TUBB3 (Affinity Capture-MS; 2 records), ABCF3 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
NPAS1	“down-regulates quantity by repression”	TH	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for NPAS1: 87 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 1,318):

Position(s)	Effect	Δscore	Sites
19:47032268–47032270	acceptor_gain	1.0000	2
19:47032276–47032277	acceptor_loss	1.0000	6
19:47032352–47032353	donor_loss	1.0000	3
19:47042808–47042809	acceptor_loss	1.0000	6
19:47042905–47042906	donor_loss	1.0000	5
19:47019998–47019999	donor_loss	0.9900	5
19:47021170–47021171	donor_loss	0.9900	5
19:47021848–47021849	donor_loss	0.9900	6
19:47032352–47032353	donor_loss	0.9900	2
19:47036115	donor_gain	0.9900

AlphaMissense

1,020 missense substitutions predicted likely pathogenic (of 3,755 scored), across 245 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
D83	8	0.997	0.999
F149	8	0.990	0.999
D190	8	0.987	0.995
N62	8	0.975	0.995
D346	8	0.962	0.983
F151	8	0.930	0.997
F65	8	0.918	0.995
F159	8	0.912	0.998
F247	8	0.901	0.987
H354	8	0.889	0.974
F134	8	0.845	0.949
H343	8	0.845	0.934
F307	8	0.823	0.947
E61	7	0.988	0.996
E164	7	0.987	0.999
K84	7	0.974	1.000
E176	7	0.955	0.991
F183	7	0.954	0.981
F100	7	0.941	0.977
W379	7	0.936	0.983

HPA cancer prognostics

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

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	2.24e-05
Lung Adenocarcinoma (TCGA)	unfavorable	0.000101
Breast Invasive Carcinoma (validation)	favorable	0.000945

Disease associations

OMIM: gene MIM:603346 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST011126_31	Caffeine consumption from coffee or tea	1e-11
GCST010703_186	Brain morphology (MOSTest)	2e-8

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	4
Valproic Acid	increases methylation, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression	1
aflatoxin B2	affects methylation	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Camptothecin	increases expression	1
Carmustine	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Etoposide	increases expression	1

Clinical trials (associated diseases)

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