NAB2

Summary

NAB2 (NGFI-A binding protein 2, HGNC:7627) is a protein-coding gene on chromosome 12q13.3, encoding NGFI-A-binding protein 2 (Q15742). Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2.

This gene encodes a member of the family of NGFI-A binding (NAB) proteins, which function in the nucleus to repress transcription induced by some members of the EGR (early growth response) family of transactivators. NAB proteins can homo- or hetero-multimerize with other EGR or NAB proteins through a conserved N-terminal domain, and repress transcription through two partially redundant C-terminal domains. Transcriptional repression by the encoded protein is mediated in part by interactions with the nucleosome remodeling and deactylase (NuRD) complex. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 4665 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 52 total
• Phenotypes (HPO): 29
• MANE Select transcript: NM_005967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7627
Approved symbol	NAB2
Name	NGFI-A binding protein 2
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	MADER
Ensembl gene	ENSG00000166886
Ensembl biotype	protein_coding
OMIM	602381
Entrez	4665

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000300131, ENST00000342556, ENST00000554718, ENST00000554839, ENST00000555857, ENST00000862010, ENST00000953388

RefSeq mRNA: 2 — MANE Select: NM_005967 NM_001330305, NM_005967

CCDS: CCDS81701, CCDS8930

Canonical transcript exons

ENST00000300131 — 7 exons

Exon	Start	End
ENSE00001107433	57091125	57091998
ENSE00001107435	57089114	57089354
ENSE00001107438	57092448	57092581
ENSE00002530185	57094612	57095476
ENSE00003568964	57093407	57093598
ENSE00003576337	57093063	57093195
ENSE00003597907	57092917	57092968

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 94.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3271 / max 201.5855, expressed in 1783 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126140	7.3947	1550
126139	4.4664	1584
126138	1.6820	752
126142	1.0662	349
126141	0.7178	253

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.78	gold quality
cerebellar hemisphere	UBERON:0002245	94.54	gold quality
cerebellar cortex	UBERON:0002129	94.51	gold quality
left ovary	UBERON:0002119	94.30	gold quality
right ovary	UBERON:0002118	94.27	gold quality
lower esophagus mucosa	UBERON:0035834	94.06	gold quality
cerebellum	UBERON:0002037	93.74	gold quality
popliteal artery	UBERON:0002250	92.65	gold quality
endocervix	UBERON:0000458	92.64	gold quality
tibial artery	UBERON:0007610	92.63	gold quality
left uterine tube	UBERON:0001303	92.57	gold quality
descending thoracic aorta	UBERON:0002345	92.37	gold quality
body of uterus	UBERON:0009853	92.37	gold quality
adenohypophysis	UBERON:0002196	92.25	gold quality
ganglionic eminence	UBERON:0004023	92.11	gold quality
aorta	UBERON:0000947	92.03	gold quality
right coronary artery	UBERON:0001625	91.76	gold quality
ectocervix	UBERON:0012249	91.64	gold quality
nerve	UBERON:0001021	91.63	gold quality
tibial nerve	UBERON:0001323	91.63	gold quality
pituitary gland	UBERON:0000007	91.61	gold quality
right uterine tube	UBERON:0001302	91.51	gold quality
ascending aorta	UBERON:0001496	91.45	gold quality
thoracic aorta	UBERON:0001515	91.34	gold quality
skin of leg	UBERON:0001511	91.17	gold quality
stromal cell of endometrium	CL:0002255	91.05	gold quality
ovary	UBERON:0000992	90.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.64	gold quality
skin of abdomen	UBERON:0001416	90.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	190.56
E-ANND-3	yes	10.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
BCAR1	Activation
EGR1	Repression
EGR2	Repression
EGR3	Repression
GFI1	Repression
RBL2	Activation
TNFSF10	Repression

Upstream regulators (CollecTRI, top): APP, BCAR1, DKK1, EGR1, EGR2, EGR3, ETS2, ETV1, IL2, SP1, SPI1

miRNA regulators (miRDB)

60 targeting NAB2, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309

Literature-anchored findings (GeneRIF, showing 35)

• mutations in the human NAB2 gene are most likely not involved in the pathogenesis of peripheral neuropathies. (PMID:12030330)
• inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. (PMID:12427750)
• Egr-1 induces the expression of its corepressor nab2 by activation of the nab2 promoter in a negative feedback loop (PMID:16260776)
• Nab2 is a novel endogenous negative regulator of Egr-1-dependent TGF-beta signaling responsible for setting the intensity of fibrotic responses (PMID:19888474)
• Results suggest that in many cells of neuroectodermal and epithelial origin EGR1, EGR2, and EGR3 activate NAB2 transcription which is in turn repressed by NAB2, thus establishing a negative feedback loop. (PMID:20506119)
• p130Cas signaling induces the expression of EGR1 and NAB2 (PMID:22431919)
• A gene fusion of the transcriptional repressor NAB2 with the transcriptional activator STAT6 is the defining driver mutation of solitary fibrous tumor. (PMID:23313952)
• A NAB2-STAT6 fusion is a distinct molecular feature of solitary fibrous tumors. (PMID:23313954)
• NAB2 and EGR-1 exert opposite roles in regulating TRAIL expression in human Natural Killer cells. (PMID:23416169)
• Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion (PMID:23575898)
• 44 SFTs were studied to identify pathogenetically important genetic rearrangements. RT-PCR analysis identified a NAB2/STAT6 fusion in 37/41 cases. (PMID:23761323)
• Tumors with the most common fusion variant, NAB2ex4-STAT6ex2/3, corresponded to classic pleuropulmonary solitary fibrous tumors with diffuse fibrosis and mostly benign behavior and occurred in older patients (PMID:24513261)
• The detection of nuclear relocation of STAT6 with immunohistochemistry is a characteristic of solitary fibrous tumours (SFTs), and may serve as a diagnostic marker that indicates NAB2-STAT6 fusion and helps to discriminate SFTs from histological mimics. (PMID:24702701)
• This study validated the existence of the NAB2-STAT6 fusion gene in solitary fibrous tumors and examined its relation with pathological features. (PMID:25554652)
• There was no association between solitary fibrous tumors with either NAB2 exon 4-STAT6 exon 2 or 3 fusion and tumors with other fusions regarding the frequency of mutations in the examined genes (P = .201). (PMID:25582503)
• reverse transcriptase PCR analysis identified a nerve growth factor inducible-A binding protein 2-STAT6 gene fusion. Our case supports the utility of STAT6 immunohistochemistry as an adjunct in the diagnosis of soft-tissue SFT with loss of CD34 positivity (PMID:25667482)
• It is associated with local recurrence and late distance metastasis of brain tumors to extracranial sites. (PMID:25893823)
• also identified NAB2-STAT6 fusions in two hemangiopericytomas diagnosed in the past with a common variant of NAB2ex6-STAT6ex16/17 (PMID:26136329)
• We delineate the common and rare NAB2-STAT6 fusion variants in solitary fibrous tumors (PMID:26226844)
• the majority of intrathoracic SFTs exhibited STAT6 nuclear staining, and NAB2ex4-STAT6ex2/3 was the predominant fusion type. (PMID:26686340)
• NAB2-STAT6 fusion is a diagnostic tumor marker for papillary’ solitary fibrous tumor/hemangiopericytoma of brain. (PMID:26746203)
• Case Report: NAB2-STAT6 fusion in glioblastoma. (PMID:26817999)
• This study confirms that meningeal Meningeal solitary fibrous tumor and hemangiopericytoma represent a histopathologic continuum linked by STAT6 nuclear expression and NAB2-STAT6 fusion similar to their soft tissue counterparts. (PMID:26883114)
• Our results represented that meningeal solitary fibrous tumor/hemangiopericytoma were in a single biological spectrum with NAB2-STAT6 gene fusion as was nonmeningeal solitary fibrous tumor (PMID:26927892)
• Variants of the NAB2-STAT6 fusion gene are found in solitary fibrous tumors of the meninges. (PMID:27271270)
• Here, we demonstrate that pulmonary adenofibromas are neoplastic lesions harbouring NAB2-STAT6 fusion genes ,the molecular hallmark of solitary fibrous tumours. (PMID:28072477)
• Study characterized sequences in NAB2 that mediate its nuclear localization and determined that the KKXK motif that aligns with the NAB1 KRXK motif is necessary for NAB2 nuclear localization, while the K(X2)R motif situated 11 residues upstream is not. (PMID:30411343)
• NAB2-STAT6 fusion type was not significantly associated with recurrence-free or overall survival, but was associated with phenotype (PMID:30584643)
• NAB2-STAT6 fusion protein mediates cell proliferation and oncogenic progression via EGR-1 regulation. (PMID:32216968)
• Gene Expression in Solitary Fibrous Tumors (SFTs) Correlates with Anatomic Localization and NAB2-STAT6 Gene Fusion Variants. (PMID:33497701)
• Clinical and molecular implications of NAB2-STAT6 fusion variants in solitary fibrous tumour. (PMID:33745702)
• Lipomatous Solitary Fibrous Tumors Harbor Rare NAB2-STAT6 Fusion Variants and Show Up-Regulation of the Gene PPARG, Encoding for a Regulator of Adipocyte Differentiation. (PMID:33887215)
• Teratocarcinosarcoma-Like and Adamantinoma-Like Head and Neck Neoplasms Harboring NAB2::STAT6: Unusual Variants of Solitary Fibrous Tumor or Novel Tumor Entities? (PMID:35303277)
• Analysis of clinicopathological features and NAB2-STAT6 fusion variants of meningeal solitary fibrous tumor with ectopic salivary gland components in the cerebellopontine angle. (PMID:36056239)
• NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors. (PMID:38523251)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nab2	ENSDARG00000078076
mus_musculus	Nab2	ENSMUSG00000025402
rattus_norvegicus	Nab2	ENSRNOG00000008415
drosophila_melanogaster	nab	FBGN0259986
caenorhabditis_elegans		WBGENE00003107

Paralogs (1): NAB1 (ENSG00000138386)

Protein

Protein identifiers

NGFI-A-binding protein 2 — Q15742 (reviewed: Q15742)

Alternative names: EGR-1-binding protein 2, Melanoma-associated delayed early response protein

All UniProt accessions (1): Q15742

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2. Isoform 2 lacks repression ability.

Subunit / interactions. Homomultimers may associate with EGR1 bound to DNA.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed at low levels. Highly expressed in melanoma cell lines.

Post-translational modifications. Sumoylation by EGR2 represses EGR2 transcriptional activity in hindbrain.

Domain organisation. The NAB conserved domain 1 (NCD1) interacts with EGR1 inhibitory domain and mediates multimerization. The NAB conserved domain 2 (NCD2) is necessary for transcriptional repression.

Induction. By serum and phorbol myristate acetate (PMA) stimulation.

Similarity. Belongs to the NAB family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15742-1	1	yes
Q15742-2	2
Q15742-3	3

RefSeq proteins (2): NP_001317234, NP_005958* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006988	Nab_N	Domain
IPR006989	NAB_co-repressor_dom	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR038398	NCD2_sf	Homologous_superfamily
IPR039040	NAB_fam	Family

Pfam: PF04904, PF04905

UniProt features (23 total): region of interest 7, modified residue 6, cross-link 3, splice variant 3, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15742-F1	64.17	0.29

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 (9): 6, 157, 159, 162, 171, 479, 379, 517, 517

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9675108	Nervous system development

MSigDB gene sets: 340 (showing top): RNGTGGGC_UNKNOWN, AAGCAAT_MIR137, AMIT_DELAYED_EARLY_GENES, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_NEUROGENESIS, NAGASHIMA_NRG1_SIGNALING_UP, GGGTGGRR_PAX4_03, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOBP_REPLACEMENT_OSSIFICATION, MODULE_66, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, MODULE_75, GOBP_BONE_DEVELOPMENT

GO Biological Process (7): endochondral ossification (GO:0001958), regulation of DNA-templated transcription (GO:0006355), Schwann cell differentiation (GO:0014037), negative regulation of transcription by RNA polymerase III (GO:0016480), myelination (GO:0042552), regulation of epidermis development (GO:0045682), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (4): transcription coregulator activity (GO:0003712), transcription corepressor activity (GO:0003714), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1
Nervous system development	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
Signal Transduction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
negative regulation of DNA-templated transcription	2
replacement ossification	1
endochondral bone morphogenesis	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
peripheral nervous system development	1
glial cell differentiation	1
regulation of transcription by RNA polymerase III	1
transcription by RNA polymerase III	1
axon ensheathment	1
epidermis development	1
regulation of developmental process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription regulator activity	1
transcription coregulator activity	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAB2	EGR1	P18146	965
NAB2	EGR2	P11161	954
NAB2	STAT6	P42226	931
NAB2	EGR3	Q06889	917
NAB2	ZC3H14	Q6PJT7	845
NAB2	EGR4	Q05215	844
NAB2	NXF1	Q9UBU9	798
NAB2	CHD3	Q12873	732
NAB2	CELF1	Q92879	661
NAB2	CD99L2	Q8TCZ2	658
NAB2	CHD4	Q14839	657
NAB2	CD99	P14209	647
NAB2	STAT2	P52630	637
NAB2	INTS13	Q9NVM9	636
NAB2	PABPC1	P11940	629

IntAct

306 interactions, top by confidence:

A	B	Type	Score
NAB2	RFC5	psi-mi:“MI:0915”(physical association)	0.830
RFC5	NAB2	psi-mi:“MI:0915”(physical association)	0.830
NAB2	PHF1	psi-mi:“MI:0915”(physical association)	0.780
NAB2	FAM200C	psi-mi:“MI:0915”(physical association)	0.780
ZMYND19	NAB2	psi-mi:“MI:0915”(physical association)	0.780
TCHP	NAB2	psi-mi:“MI:0915”(physical association)	0.780
NAB2	ZMYND19	psi-mi:“MI:0915”(physical association)	0.780
NAB2	TCHP	psi-mi:“MI:0915”(physical association)	0.780
CWF19L2	NAB2	psi-mi:“MI:0915”(physical association)	0.720
NAB2	PIN1	psi-mi:“MI:0915”(physical association)	0.720
TGIF2LY	NAB2	psi-mi:“MI:0915”(physical association)	0.720
NAB2	PHOSPHO2	psi-mi:“MI:0915”(physical association)	0.720
LENG1	NAB2	psi-mi:“MI:0915”(physical association)	0.720
NAB2	NME7	psi-mi:“MI:0915”(physical association)	0.720
NAB2	CWF19L2	psi-mi:“MI:0915”(physical association)	0.720
PIN1	NAB2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (156): NAB2 (Two-hybrid), NAB2 (Two-hybrid), NAB2 (Two-hybrid), NAB2 (Two-hybrid), NEDD9 (Two-hybrid), PHF1 (Two-hybrid), PIN1 (Two-hybrid), RFC5 (Two-hybrid), JAKMIP2 (Two-hybrid), MORF4L1 (Two-hybrid), RBPMS (Two-hybrid), NME7 (Two-hybrid), CCHCR1 (Two-hybrid), TTC19 (Two-hybrid), ZBED8 (Two-hybrid)

ESM2 similar proteins: A0A8I3QA39, A2A6T1, A2A9T0, A2AHG0, A4FUG8, A5PKL7, A6NKD9, A7MCY6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O15049, O60299, O75145, O94964, P60469, P70298, Q15742, Q1LZH7, Q3LUD3, Q3LUD4, Q5JTD0, Q5RCR6, Q61127, Q63ZY3, Q6DG50, Q6DIS8, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IZD0, Q8K1Q4, Q8K371, Q91YU6

Diamond homologs: O35589, Q13506, Q15742, Q59E55, Q61122, Q61127, Q62722, Q22002

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
EGR3	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
EGR2	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
EGR3	“down-regulates quantity by repression”	NAB2	“transcriptional regulation”
EGR2	“down-regulates quantity by repression”	NAB2	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	EGR1	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	EGR3	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	EGR2	“transcriptional regulation”
NAB2	“up-regulates quantity by expression”	BCAR1	“transcriptional regulation”
BCAR1	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	TNFSF10	“transcriptional regulation”
IL2	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
SPI1	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	GFI1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1001 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57089355:G:GG	donor_gain	1.0000
12:57089356:T:G	donor_gain	1.0000
12:57089944:A:T	donor_gain	1.0000
12:57091123:A:AG	acceptor_gain	1.0000
12:57091124:G:GG	acceptor_gain	1.0000
12:57091124:G:GT	acceptor_loss	1.0000
12:57091124:GGCCC:G	acceptor_gain	1.0000
12:57091999:G:C	donor_loss	1.0000
12:57092443:CACA:C	acceptor_loss	1.0000
12:57092445:C:G	acceptor_gain	1.0000
12:57092445:CA:C	acceptor_loss	1.0000
12:57092446:A:AC	acceptor_loss	1.0000
12:57092446:A:AG	acceptor_gain	1.0000
12:57092447:G:A	acceptor_loss	1.0000
12:57092447:G:GA	acceptor_gain	1.0000
12:57092447:GCTCA:G	acceptor_gain	1.0000
12:57092579:CAGGT:C	donor_loss	1.0000
12:57092580:AG:A	donor_loss	1.0000
12:57092581:GG:G	donor_loss	1.0000
12:57092582:GT:G	donor_loss	1.0000
12:57092583:T:G	donor_loss	1.0000
12:57092907:A:AG	acceptor_gain	1.0000
12:57092913:TCAG:T	acceptor_loss	1.0000
12:57092915:A:AG	acceptor_gain	1.0000
12:57092916:G:GT	acceptor_gain	1.0000
12:57092916:GGCTT:G	acceptor_gain	1.0000
12:57092965:AGAGG:A	donor_loss	1.0000
12:57092966:GAG:G	donor_gain	1.0000
12:57092969:G:GA	donor_loss	1.0000
12:57092969:G:GG	donor_gain	1.0000

AlphaMissense

3370 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57091151:C:A	P37H	1.000
12:57091166:A:T	E42V	1.000
12:57091169:T:C	L43P	1.000
12:57091175:T:A	L45Q	1.000
12:57091175:T:C	L45P	1.000
12:57091181:G:C	R47P	1.000
12:57091184:T:A	V48D	1.000
12:57091187:T:A	L49Q	1.000
12:57091187:T:C	L49P	1.000
12:57091187:T:G	L49R	1.000
12:57091190:A:C	Q50P	1.000
12:57091195:G:C	A52P	1.000
12:57091196:C:A	A52D	1.000
12:57091202:T:A	L54H	1.000
12:57091202:T:C	L54P	1.000
12:57091222:T:C	F61L	1.000
12:57091223:T:C	F61S	1.000
12:57091223:T:G	F61C	1.000
12:57091224:C:A	F61L	1.000
12:57091224:C:G	F61L	1.000
12:57091234:G:A	G65R	1.000
12:57091234:G:C	G65R	1.000
12:57091235:G:A	G65E	1.000
12:57091235:G:T	G65V	1.000
12:57091237:G:A	G66R	1.000
12:57091237:G:C	G66R	1.000
12:57091237:G:T	G66W	1.000
12:57091238:G:A	G66E	1.000
12:57091240:G:C	D67H	1.000
12:57091241:A:C	D67A	1.000

dbSNP variants (sampled 300 via entrez): RS1001081235 (12:57092089 T>C), RS1001627481 (12:57094514 C>T), RS1001796467 (12:57095300 G>A), RS1001912456 (12:57095558 C>A,T), RS1002868067 (12:57088896 C>T), RS1003040869 (12:57094457 C>T), RS1003253155 (12:57090122 T>C), RS1003615189 (12:57089923 G>A), RS1003991271 (12:57089742 C>T), RS1004040050 (12:57089567 A>G), RS1004216903 (12:57090917 A>G), RS1004898851 (12:57087657 G>C), RS1005026374 (12:57092776 A>G), RS1005225923 (12:57089722 G>A), RS1005715062 (12:57090548 C>T)

Disease associations

OMIM: gene MIM:602381 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000016	Urinary retention
HP:0000290	Abnormal forehead morphology
HP:0000651	Diplopia
HP:0001824	Weight loss
HP:0001943	Hypoglycemia
HP:0001945	Fever
HP:0001988	Recurrent hypoglycemia
HP:0002019	Constipation
HP:0002585	Abnormal peritoneum morphology
HP:0002664	Neoplasm
HP:0002896	Neoplasm of the liver
HP:0003419	Low back pain
HP:0004375	Neoplasm of the nervous system
HP:0004912	Hypophosphatemic rickets
HP:0007185	Loss of consciousness
HP:0008775	Abnormal prostate morphology
HP:0010784	Uterine neoplasm
HP:0010787	Genital neoplasm
HP:0012125	Prostate cancer
HP:0012378	Fatigue
HP:0030166	Night sweats
HP:0030795	Reduced C-peptide level
HP:0031459	Soft tissue neoplasm
HP:0031501	Pelvic mass
HP:0040216	Hypoinsulinemia
HP:0045026	Abnormal mediastinum morphology
HP:0100526	Neoplasm of the lung
HP:0100527	Neoplasia of the pleura
HP:0100650	Vaginal neoplasm

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001316_2	IgE levels	2.000000e-12
GCST002539_15	Schizophrenia	2.000000e-12
GCST005212_34	Asthma	4.000000e-09
GCST006803_97	Schizophrenia	3.000000e-11
GCST006862_2	Asthma	6.000000e-09
GCST007563_7	Allergic disease (asthma, hay fever or eczema)	1.000000e-09
GCST007564_27	Asthma or allergic disease (pleiotropy)	8.000000e-13
GCST007993_20	Asthma (adult onset)	6.000000e-09
GCST007995_40	Asthma (childhood onset)	7.000000e-17
GCST008103_173	Bipolar disorder	7.000000e-06
GCST008916_110	Asthma	1.000000e-27
GCST008916_2	Asthma	2.000000e-08
GCST009720_56	Asthma	1.000000e-28
GCST009798_10	Asthma	3.000000e-29

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1002011	adult onset asthma

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1059513	NAB2, STAT6	3	2.25	1	esomeprazole

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, affects expression, increases expression	4
Arsenic Trioxide	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
urushiol	decreases expression	1
arsenite	decreases reaction, increases expression	1
1,6-hexamethylene diisocyanate	increases methylation	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
torcetrapib	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
PCI 5002	affects cotreatment, increases expression	1
Imatinib Mesylate	increases expression	1
Bortezomib	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases reaction, increases expression	1
Leflunomide	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzene	increases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression, affects cotreatment	1
Dexamethasone	decreases expression	1
Estrogens	decreases reaction, increases expression	1
Hydrogen Peroxide	affects expression	1
Rotenone	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6JI	SFT-T1	Cancer cell line	Male
CVCL_C6JJ	SFT-T2	Cancer cell line	Female
CVCL_D4AC	SFT-S1	Cancer cell line	Female
CVCL_E6MC	NCC-SFT1-C1	Cancer cell line	Female

Clinical trials (associated diseases)

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