NKX2-2

Summary

NKX2-2 (NK2 homeobox 2, HGNC:7835) is a protein-coding gene on chromosome 20p11.22, encoding Homeobox protein Nkx-2.2 (O95096). Transcriptional activator involved in the development of insulin-producting beta cells in the endocrine pancreas.

The protein encoded by this gene contains a homeobox domain and may be involved in the morphogenesis of the central nervous system. This gene is found on chromosome 20 near NKX2-4, and these two genes appear to be duplicated on chromosome 14 in the form of TITF1 and NKX2-8. The encoded protein is likely to be a nuclear transcription factor.

Source: NCBI Gene 4821 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal diabetes mellitus (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 55 total — 1 pathogenic, 1 likely-pathogenic
• Transcription factor: yes — 29 downstream targets (CollecTRI)
• MANE Select transcript: NM_002509

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7835
Approved symbol	NKX2-2
Name	NK2 homeobox 2
Location	20p11.22
Locus type	gene with protein product
Status	Approved
Aliases	NKX2.2
Ensembl gene	ENSG00000125820
Ensembl biotype	protein_coding
OMIM	604612
Entrez	4821

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377142

RefSeq mRNA: 2 — MANE Select: NM_002509 NM_001424412, NM_002509

CCDS: CCDS13145

Canonical transcript exons

ENST00000377142 — 2 exons

Exon	Start	End
ENSE00001472897	21511017	21512485
ENSE00001472902	21513411	21514064

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 96.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1019 / max 181.3458, expressed in 153 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186611	0.5492	129
186610	0.3805	101
186609	0.1319	61
186608	0.0357	25
186607	0.0046	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	96.40	gold quality
subthalamic nucleus	UBERON:0001906	92.94	gold quality
medulla oblongata	UBERON:0001896	92.59	gold quality
superior vestibular nucleus	UBERON:0007227	92.14	gold quality
ventral tegmental area	UBERON:0002691	90.95	gold quality
inferior olivary complex	UBERON:0002127	90.92	gold quality
spinal cord	UBERON:0002240	90.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.34	gold quality
lateral globus pallidus	UBERON:0002476	89.70	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.47	gold quality
globus pallidus	UBERON:0001875	87.25	gold quality
pons	UBERON:0000988	87.24	gold quality
substantia nigra pars compacta	UBERON:0001965	86.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.31	gold quality
medial globus pallidus	UBERON:0002477	86.08	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.23	gold quality
midbrain	UBERON:0001891	84.46	gold quality
cranial nerve II	UBERON:0000941	83.70	gold quality
substantia nigra	UBERON:0002038	83.64	gold quality
type B pancreatic cell	CL:0000169	81.16	gold quality
parietal lobe	UBERON:0001872	81.11	gold quality
islet of Langerhans	UBERON:0000006	80.83	gold quality
CA1 field of hippocampus	UBERON:0003881	80.83	gold quality
postcentral gyrus	UBERON:0002581	80.69	gold quality
hypothalamus	UBERON:0001898	79.93	gold quality
Ammon’s horn	UBERON:0001954	78.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	78.20	gold quality
middle frontal gyrus	UBERON:0002702	77.90	gold quality
amygdala	UBERON:0001876	77.88	gold quality
temporal lobe	UBERON:0001871	76.18	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	425.60
E-GEOD-83139	yes	8.47
E-ANND-3	yes	8.16
E-GEOD-125970	yes	7.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

29 targets.

Target	Regulation
AKT1
ARX
CCND2
CD52	Unknown
CDKN1B
ERMN	Activation
GAST
GHRL
INS	Unknown
LMX1A
LMX1B
MAFA
MBP
NKX2-2
NKX6-1	Activation
NPPA	Activation
PAX1
PI3
PLP1	Activation
PPY
PRKCG
RAB34
REG3A
SHH
SIRT2
SLIT1	Activation
SST
SULF1	Activation
TRIB3

JASPAR motifs

Motif	Name	Family
MA1645.1	NKX2-2	NK
MA1645.2	NKX2-2	NK

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): CTNNB1, FOXA1, FOXA2, GLI2, ISL1, NEUROG3, NKX2-2, PAX1, SHH, SOX10

Literature-anchored findings (GeneRIF, showing 22)

• Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in Ewing’s sarcoma. (PMID:16697960)
• EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewing’s sarcoma (PMID:18414662)
• NKX2.2 functions in immature endocrine cells to control neuroendocrine differentiation in normal intestine and is expressed in most neuroendocrine tumors of the gut (PMID:18987169)
• several genes that are known to be regulated by DNA methylation were up-regulated dramatically by integrin alpha6beta4 expression, including S100A4, FST, PDLIM4, CAPG, and Nkx2.2. (PMID:19011242)
• expression may assist in the determination of the primary tumor site in patients with neuroendocrine tumor metastases of unknown origin: negative would suggest a bronchopulmonary primary, whereas positive would suggest a gastrointestinal primary (PMID:20599218)
• NKX2-1, NKX2-2, and MEF2C define oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL). (PMID:21481790)
• The NKX2-2 can induce desired neuronal lineages from most expressing neural progenitor cells by a mechanism resembling developmental binary cell-fate switching. (PMID:21624811)
• NKX2.2 is a valuable marker for Ewing sarcoma, with a sensitivity of 93% and a specificity of 89%, and aids in the differential diagnosis of small round cell tumors. (PMID:22446943)
• NKX2-2 and MNX1 are etiological genes for neonatal diabetes. (PMID:24411943)
• Our study suggests that CGT expression is controlled by balanced expression of the negative modulator OLIG2 and positive regulator Nkx2.2, providing new insights into how expression of GalCer is tightly regulated in cell-type- and stage-specific manners. (PMID:24821492)
• lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate (PMID:24982138)
• NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells (PMID:26847175)
• nuclear import of Nkx2-2 is mediated not only by the classical import pathway but also directly by imp beta1 or imp 13 (PMID:27956177)
• NKX2.2 is a useful and very sensitive marker for Ewing sarcoma (PMID:28616785)
• The Utility of NKX2.2 and TLE1 Immunohistochemistry in the Differentiation of Ewing Sarcoma and Synovial Sarcoma. (PMID:28800015)
• NKX2.2 demonstrated moderate or strong nuclear positivity in 91.2% of the tumors (PMID:28864350)
• Nkx-2.2 homedomain protein NKX2.2 (NKX2.2) had high sensitivity (100%) and moderate specificity (85%) for the diagnosis of Ewing sarcoma (ES) in cytologic material. (PMID:30376220)
• Study found that activation of Gli2 transcription factor induces the expression of Nkx2.2. inducing Ewing-like sarcomas. (PMID:30683671)
• Reversible expansion of pancreatic islet progenitors derived from human induced pluripotent stem cells. (PMID:32065490)
• Rapid induction of gliogenesis in OLIG2 and NKX2.2-expressing progenitors-derived spheroids. (PMID:32716131)
• Does PAX7 and NKX2.2 immunoreactivity in Ewing sarcoma have prognostic significance? (PMID:34985580)
• A novel stop-loss mutation in NKX2-2 gene as a cause of neonatal diabetes mellitus: molecular characterization and structural analysis. (PMID:37821536)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkx2.2a	ENSDARG00000053298
mus_musculus	Nkx2-2	ENSMUSG00000027434
rattus_norvegicus	Nkx2-2	ENSRNOG00000012728
drosophila_melanogaster	NK7.1	FBGN0024321
drosophila_melanogaster	HGTX	FBGN0040318
drosophila_melanogaster	scro	FBGN0287186
caenorhabditis_elegans	ceh-9	WBGENE00000434
caenorhabditis_elegans		WBGENE00000447
caenorhabditis_elegans		WBGENE00000450
caenorhabditis_elegans		WBGENE00000584

Paralogs (13): NKX3-2 (ENSG00000109705), NKX2-3 (ENSG00000119919), NKX2-4 (ENSG00000125816), NKX2-8 (ENSG00000136327), NKX2-1 (ENSG00000136352), NKX6-2 (ENSG00000148826), NKX6-1 (ENSG00000163623), NKX6-3 (ENSG00000165066), NKX3-1 (ENSG00000167034), NKX2-6 (ENSG00000180053), NKX2-5 (ENSG00000183072), NKX1-2 (ENSG00000229544), NKX1-1 (ENSG00000235608)

Protein

Protein identifiers

Homeobox protein Nkx-2.2 — O95096 (reviewed: O95096)

Alternative names: Homeobox protein NK-2 homolog B

All UniProt accessions (1): O95096

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator involved in the development of insulin-producting beta cells in the endocrine pancreas. May also be involved in specifying diencephalic neuromeric boundaries, and in controlling the expression of genes that play a role in axonal guidance. Binds to elements within the NEUROD1 promoter.

Subunit / interactions. Interacts with OLIG2.

Subcellular location. Nucleus.

Domain organisation. The homeodomain is essential for interaction with OLIG2.

Similarity. Belongs to the NK-2 homeobox family.

RefSeq proteins (2): NP_001411341, NP_002500* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050394	Homeobox_NK-like	Family

Pfam: PF00046

UniProt features (5 total): region of interest 2, chain 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95096-F1	64.62	0.23

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-210745	Regulation of gene expression in beta cells
R-HSA-210746	Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells

MSigDB gene sets: 265 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, WWTAAGGC_UNKNOWN, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_TYPE_B_PANCREATIC_CELL_DEVELOPMENT, GOBP_GLIAL_CELL_DEVELOPMENT, TATTATA_MIR374, GOBP_NEUROGENESIS

GO Biological Process (34): type B pancreatic cell development (GO:0003323), pancreatic A cell fate commitment (GO:0003326), type B pancreatic cell fate commitment (GO:0003327), pancreatic PP cell fate commitment (GO:0003329), regulation of transcription by RNA polymerase II (GO:0006357), smoothened signaling pathway (GO:0007224), brain development (GO:0007420), response to glucose (GO:0009749), positive regulation of gene expression (GO:0010628), oligodendrocyte development (GO:0014003), spinal cord motor neuron differentiation (GO:0021522), spinal cord oligodendrocyte cell fate specification (GO:0021530), optic nerve development (GO:0021554), cell differentiation (GO:0030154), positive regulation of epithelial cell differentiation (GO:0030858), response to progesterone (GO:0032570), negative regulation of neuron differentiation (GO:0045665), positive regulation of neuron differentiation (GO:0045666), digestive tract development (GO:0048565), neuron fate specification (GO:0048665), astrocyte differentiation (GO:0048708), positive regulation of oligodendrocyte differentiation (GO:0048714), ventral spinal cord interneuron fate determination (GO:0060580), neuroendocrine cell differentiation (GO:0061101), type B pancreatic cell differentiation (GO:0003309), regulation of DNA-templated transcription (GO:0006355), nervous system development (GO:0007399), spinal cord oligodendrocyte cell differentiation (GO:0021529), central nervous system neuron differentiation (GO:0021953), neuron differentiation (GO:0030182), endocrine pancreas development (GO:0031018), positive regulation of transcription by RNA polymerase II (GO:0045944), cell development (GO:0048468), oligodendrocyte differentiation (GO:0048709)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of beta-cell development	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epithelial cell fate commitment	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
type B pancreatic cell differentiation	2
regulation of DNA-templated transcription	2
positive regulation of cell differentiation	2
neuron differentiation	2
regulation of neuron differentiation	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
epithelial cell development	1
pancreatic A cell differentiation	1
pancreatic PP cell differentiation	1
transcription by RNA polymerase II	1
cell surface receptor signaling pathway	1
central nervous system development	1
animal organ development	1
head development	1
response to hexose	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
glial cell development	1
oligodendrocyte differentiation	1
cell differentiation in spinal cord	1
ventral spinal cord development	1
central nervous system neuron differentiation	1
spinal cord oligodendrocyte cell differentiation	1
oligodendrocyte cell fate specification	1
cranial nerve development	1
cellular developmental process	1
epithelial cell differentiation	1
regulation of epithelial cell differentiation	1
response to steroid hormone	1
response to ketone	1
negative regulation of cell differentiation	1
tube development	1
digestive system development	1
cell fate specification	1
neuron fate commitment	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

1644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKX2-2	TLE3	Q04726	972
NKX2-2	LMX1B	O60663	895
NKX2-2	PAX4	O43316	885
NKX2-2	ISL1	P20663	876
NKX2-2	HDAC1	Q13547	873
NKX2-2	PAX6	P26367	868
NKX2-2	DNMT3A	Q9Y6K1	865
NKX2-2	OLIG2	Q13516	856
NKX2-2	ASCL1	P50553	851
NKX2-2	FOXA2	Q9Y261	847
NKX2-2	SHH	Q15465	821
NKX2-2	NEUROG3	Q9Y4Z2	807
NKX2-2	OLIG1	Q8TAK6	790
NKX2-2	NEUROD1	Q13562	778
NKX2-2	LMX1A	Q8TE12	754

IntAct

19 interactions, top by confidence:

A	B	Type	Score
NKX2-2	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
	NKX2-2	psi-mi:“MI:0915”(physical association)	0.370
IFNL1	NKX2-2	psi-mi:“MI:0915”(physical association)	0.370
IL15	NKX2-2	psi-mi:“MI:0915”(physical association)	0.370
IL17B	NKX2-2	psi-mi:“MI:0915”(physical association)	0.370
XCL2	NKX2-2	psi-mi:“MI:0915”(physical association)	0.370
AKT1	NKX2-2	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	NKX2-2	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	NKX2-2	psi-mi:“MI:2364”(proximity)	0.270
NKX2-2	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	NKX2-2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (7): NKX2-2 (Affinity Capture-MS), NKX2-2 (Negative Genetic), NKX2-2 (Affinity Capture-MS), NKX2-2 (Proximity Label-MS), NKX2-2 (Affinity Capture-Western), SIN3A (Affinity Capture-Western), HDAC1 (Affinity Capture-Western)

ESM2 similar proteins: A0A8V0YY16, A0JPN1, A7MB54, A8MTJ6, O35762, O42115, O57601, O88181, O95096, P09065, P23683, P28356, P31311, P31315, P32443, P39020, P42581, P42586, P43697, P48031, P49640, P50222, P50476, P52951, P52954, P52955, P78426, P81067, P81068, P97334, Q14549, Q14774, Q1KKY1, Q1XID0, Q2NKI2, Q2VL76, Q2VL80, Q4V5A3, Q5SQQ9, Q60554

Diamond homologs: A1YF16, A1YG93, A2RU54, A2T764, A6NCS4, A6NHT5, G5EE18, O02786, O15522, O17319, O35767, O43763, O57601, O70218, O70584, O93590, O95096, P13297, P22711, P22808, P22809, P23410, P23441, P28360, P28361, P28362, P35548, P35993, P40764, P41936, P42581, P42582, P42583, P42584, P42586, P42587, P43687, P43688, P43697, P43698

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NKX2-2	“up-regulates quantity by expression”	ERMN	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	13
Likely benign	29
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3068495	NC_000020.10:g.20158646_24080787del	Pathogenic
2736955	NM_002509.4(NKX2-2):c.356del (p.Pro119fs)	Likely pathogenic

SpliceAI

239 predictions. Top by Δscore:

Variant	Effect	Δscore
20:21512482:TGCA:T	acceptor_gain	1.0000
20:21512483:GCA:G	acceptor_gain	1.0000
20:21512484:CAC:C	acceptor_gain	1.0000
20:21512486:C:CC	acceptor_gain	1.0000
20:21513406:CTT:C	donor_loss	1.0000
20:21513407:TTA:T	donor_loss	1.0000
20:21513408:TA:T	donor_loss	1.0000
20:21513409:A:AC	donor_gain	1.0000
20:21513409:ACGGG:A	donor_loss	1.0000
20:21513410:C:CG	donor_gain	1.0000
20:21513410:CG:C	donor_gain	1.0000
20:21513410:CGGG:C	donor_gain	1.0000
20:21512481:GTGCA:G	acceptor_gain	0.9900
20:21512484:CA:C	acceptor_gain	0.9900
20:21513410:CGG:C	donor_gain	0.9900
20:21513410:CGGGA:C	donor_gain	0.9900
20:21513421:AAGGC:A	donor_gain	0.9900
20:21512480:CG:C	acceptor_gain	0.9700
20:21513403:CTACT:C	donor_loss	0.9600
20:21513404:TACTT:T	donor_loss	0.9600
20:21513405:ACTTA:A	donor_loss	0.9600
20:21513880:AGTG:A	donor_gain	0.9300
20:21512482:TGCAC:T	acceptor_gain	0.9200
20:21512483:GCACT:G	acceptor_gain	0.9200
20:21512484:CACT:C	acceptor_gain	0.9200
20:21512485:AC:A	acceptor_gain	0.9200
20:21512486:CTG:C	acceptor_gain	0.9200
20:21512487:T:A	acceptor_gain	0.9200
20:21513405:A:AC	donor_gain	0.9200
20:21513406:C:CC	donor_gain	0.9200

AlphaMissense

1755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:21512119:A:T	V209D	1.000
20:21512122:A:G	L208S	1.000
20:21512125:A:T	V207D	1.000
20:21512131:A:T	V205E	1.000
20:21512191:C:G	R185P	1.000
20:21512192:G:A	R185C	1.000
20:21512192:G:T	R185S	1.000
20:21512193:C:A	K184N	1.000
20:21512193:C:G	K184N	1.000
20:21512194:T:A	K184M	1.000
20:21512195:T:C	K184E	1.000
20:21512199:C:A	K182N	1.000
20:21512199:C:G	K182N	1.000
20:21512200:T:A	K182M	1.000
20:21512200:T:G	K182T	1.000
20:21512201:T:C	K182E	1.000
20:21512201:T:G	K182Q	1.000
20:21512203:T:C	Y181C	1.000
20:21512203:T:G	Y181S	1.000
20:21512204:A:C	Y181D	1.000
20:21512204:A:G	Y181H	1.000
20:21512204:A:T	Y181N	1.000
20:21512206:C:A	R180L	1.000
20:21512206:C:G	R180P	1.000
20:21512206:C:T	R180H	1.000
20:21512207:G:A	R180C	1.000
20:21512207:G:C	R180G	1.000
20:21512207:G:T	R180S	1.000
20:21512208:G:C	H179Q	1.000
20:21512208:G:T	H179Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000266593 (20:21512181 G>A,C,T), RS1000495673 (20:21512602 C>A,G), RS1001452826 (20:21522407 G>A,T), RS1001541483 (20:21522486 C>A,T), RS1001587248 (20:21522179 T>C), RS1001631134 (20:21516759 C>T), RS1001704039 (20:21511360 C>T), RS1001838509 (20:21521301 T>A), RS1002257842 (20:21516004 T>C), RS1002474317 (20:21521890 ACC>A,AC,ACCC), RS1002600105 (20:21513763 TTGGGGGGAGGGAC>T), RS1002812603 (20:21518909 C>G), RS1002873428 (20:21514173 AG>A), RS1002925525 (20:21513950 G>A), RS1003151386 (20:21519284 G>A)

Disease associations

OMIM: gene MIM:604612 | disease phenotypes: MIM:256450

GenCC curated gene-disease

Disease	Classification	Inheritance
neonatal diabetes mellitus	Strong	Autosomal recessive
monogenic diabetes	Strong	Autosomal recessive

Mondo (3): hyperinsulinemic hypoglycemia, familial, 1 (MONDO:0009734), neonatal diabetes mellitus (MONDO:0016391), monogenic diabetes (MONDO:0015967)

Orphanet (2): Autosomal dominant hyperinsulinism due to SUR1 deficiency (Orphanet:276575), Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency (Orphanet:276598)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002479_15	Lupus nephritis in systemic lupus erythematosus	5.000000e-06
GCST006467_2	Ewing sarcoma	4.000000e-16
GCST007556_21	Autism spectrum disorder	3.000000e-07
GCST007576_266	Chronotype	3.000000e-09
GCST007748_2	Hyperglycemia in higher physical activity	4.000000e-08
GCST009379_292	Type 2 diabetes	1.000000e-08
GCST010002_63	Refractive error	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
arsenite	increases methylation	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
(+)-JQ1 compound	decreases expression	1
Carmustine	decreases expression	1
Diazinon	increases methylation	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methapyrilene	increases methylation	1
Tretinoin	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4Q3	SEES3-1V human NKX2-2, clone1	Embryonic stem cell	Male
CVCL_A4Q4	SEES3-1V human NKX2-2, clone2	Embryonic stem cell	Male
CVCL_A4Q5	SEES3-1V human NKX2-2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06976658	PHASE2	RECRUITING	Glucokinase Activator in Monogenic Diabetes
NCT01795144	PHASE1	COMPLETED	Incretin Regulation of Insulin Secretion in Monogenic Diabetes
NCT04409795	PHASE2/PHASE3	COMPLETED	Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study
NCT03988764	Not specified	RECRUITING	Monogenic Diabetes Misdiagnosed as Type 1
NCT05586594	Not specified	NOT_YET_RECRUITING	Identifying Maturity-onset Diabetes of the Young in Emirati Patients
NCT06478121	Not specified	RECRUITING	Understanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)
NCT06746610	Not specified	RECRUITING	Screening and Molecular Diagnosis-based Individualized Precision Management of Monogenic Diabetes
NCT07492004	Not specified	RECRUITING	China Monogenic Diabetes Registry
NCT07564518	Not specified	NOT_YET_RECRUITING	Application of FreeStyle Libre 2 for Evaluating Glycemic Variability Characteristics in Patients With Extreme Glucose Metabolism Phenotypes