JADE2

Summary

JADE2 (jade family PHD finger 2, HGNC:22984) is a protein-coding gene on chromosome 5q31.1, encoding E3 ubiquitin-protein ligase Jade-2 (Q9NQC1). Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity.

Enables histone H4K12 acetyltransferase activity; histone H4K5 acetyltransferase activity; and histone H4K8 acetyltransferase activity. Contributes to histone H3K14 acetyltransferase activity. Involved in regulation of DNA biosynthetic process; regulation of DNA replication; and regulation of cell cycle. Located in nucleoplasm. Part of histone acetyltransferase complex.

Source: NCBI Gene 23338 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 45 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 103 total
• Regional missense constraint (gnomAD): 1 of 9 regions constrained (≈2% of expected missense variation)
• Expression (HPA): Low tissue specificity — highest in claustrum, parieto-temporal junction (white matter), paraventricular nucleus
• GTEx eGene: eQTL in 19 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.25 (highly constrained)
• MANE Select transcript: NM_001388185
• Notable: 103 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22984
Approved symbol	JADE2
Name	jade family PHD finger 2
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0239, JADE-2
Ensembl gene	ENSG00000043143
Ensembl biotype	protein_coding
OMIM	610515
Entrez	23338

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 40 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000681547

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

ENST00000681547, ENST00000282605, ENST00000361895, ENST00000395003, ENST00000402835, ENST00000430087, ENST00000431355, ENST00000453515, ENST00000470876, ENST00000512386, ENST00000515554, ENST00000612830, ENST00000680418, ENST00000681019, ENST00000681498, ENST00000681792, ENST00000681820, ENST00000892462, ENST00000892463, ENST00000892464, ENST00000892465, ENST00000892466, ENST00000892467, ENST00000892468, ENST00000892470, ENST00000892471, ENST00000892474, ENST00000892476, ENST00000892478, ENST00000892479, ENST00000892481, ENST00000930756, ENST00000930757, ENST00000930758, ENST00000930759, ENST00000930760, ENST00000930761, ENST00000930762, ENST00000946716, ENST00000946717, ENST00000946718, ENST00000946719, ENST00001028122, ENST00001065911, ENST00001065912, ENST00001065913, ENST00001065914, ENST00001126604, ENST00001138486

RefSeq mRNA: 23 — MANE Select: NM_001388185 NM_001289984, NM_001289985, NM_001308143, NM_001388185, NM_001388186, NM_001388187, NM_001388188, NM_001437914, NM_001437915, NM_001437916, NM_001437917, NM_001437920, NM_001437921, NM_001437922, NM_001437923, NM_001437924, NM_001437925, NM_001437926, NM_001437927, NM_001437928, NM_001437929, NM_001437930, NM_015288

CCDS: CCDS4176, CCDS75305, CCDS78061, CCDS93782

Canonical transcript exons

ENST00000681547 — 12 exons

Exon	Start	End
ENSE00001006706	134537989	134538083
ENSE00001274664	134573645	134573762
ENSE00001274680	134562200	134562367
ENSE00001274730	134564494	134564610
ENSE00001274738	134560746	134560957
ENSE00003465802	134552052	134552209
ENSE00003520701	134535858	134535915
ENSE00003540202	134576768	134576896
ENSE00003603447	134566116	134566580
ENSE00003644936	134559830	134559990
ENSE00003915168	134525670	134526011
ENSE00003922142	134578494	134583227

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 94.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5110 / max 145.1104, expressed in 1751 samples.

Highest expression (Bgee): palpebral conjunctiva, middle temporal gyrus, endothelial cell, granulocyte, Brodmann (1909) area 10.

Genetic regulation across tissues (GTEx eQTL / sQTL)

JADE2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	8.3e-33	-0.49	5:134553551:C:A
Cells EBV-transformed lymphocytes	sqtl	2.6e-06	+0.52	5:134561211:T:A
Artery Tibial	sqtl	7.3e-06	+0.35	5:134512969:C:T
Colon Transverse	eqtl	6.8e-05	-0.14	5:134514931:G:A
Adipose Subcutaneous	eqtl	1.7e-04	-0.13	5:134509421:T:C
Adipose Visceral Omentum	eqtl	2.3e-04	-0.12	5:134509421:T:C
Nerve Tibial	eqtl	8.7e-04	-0.14	5:134520119:T:C
Nerve Tibial	sqtl	1.3e-03	+0.34	5:134512969:C:T
Thyroid	sqtl	1.4e-03	+0.30	5:134509689:A:G
Brain Cerebellum	eqtl	1.5e-03	+0.28	5:134585313:C:T
Esophagus Muscularis	eqtl	2.6e-03	-0.11	5:134514931:G:A
Cells Cultured fibroblasts	eqtl	4.5e-03	-0.10	5:134518186:C:T
Brain Cerebellar Hemisphere	eqtl	5.1e-03	-0.16	5:134496385:T:A
Lung	eqtl	5.7e-03	-0.14	5:134503859:G:A
Brain Caudate basal ganglia	eqtl	1.2e-02	-0.37	5:134492996:G:T
Testis	eqtl	1.7e-02	+0.10	5:133848574:GA:G
Brain Spinal cord cervical c-1	eqtl	1.8e-02	-0.63	5:134680525:G:A
Heart Atrial Appendage	eqtl	1.9e-02	+0.53	5:135097012:C:T
Artery Tibial	eqtl	3.3e-02	-0.09	5:134509421:T:C
Small Intestine Terminal Ileum	eqtl	3.3e-02	-0.59	5:133990390:G:T

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
58584	8.1864	1583
58582	1.7747	883
58583	1.3192	738
58586	0.7732	423
58587	0.7092	384
58585	0.6878	360
58590	0.0274	12
58588	0.0201	11
58589	0.0130	7

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	94.01	gold quality
middle temporal gyrus	UBERON:0002771	93.75	gold quality
endothelial cell	CL:0000115	93.06	gold quality
granulocyte	CL:0000094	92.32	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.72	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.59	gold quality
eye	UBERON:0000970	91.47	gold quality
sural nerve	UBERON:0015488	91.11	gold quality
CA1 field of hippocampus	UBERON:0003881	90.84	gold quality
parotid gland	UBERON:0001831	90.56	gold quality
lymph node	UBERON:0000029	90.29	gold quality
metanephric glomerulus	UBERON:0004736	89.82	gold quality
renal glomerulus	UBERON:0000074	89.80	gold quality
blood	UBERON:0000178	89.52	gold quality
superficial temporal artery	UBERON:0001614	89.33	gold quality
right adrenal gland cortex	UBERON:0035827	89.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.96	gold quality
visceral pleura	UBERON:0002401	88.93	gold quality
postcentral gyrus	UBERON:0002581	88.93	gold quality
right adrenal gland	UBERON:0001233	88.87	gold quality
primary visual cortex	UBERON:0002436	88.70	gold quality
seminal vesicle	UBERON:0000998	88.65	gold quality
left adrenal gland cortex	UBERON:0035825	88.54	gold quality
entorhinal cortex	UBERON:0002728	88.49	gold quality
adrenal cortex	UBERON:0001235	88.48	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.43	gold quality
parietal lobe	UBERON:0001872	88.39	gold quality
superior frontal gyrus	UBERON:0002661	88.15	gold quality
adult organism	UBERON:0007023	88.03	gold quality
left adrenal gland	UBERON:0001234	87.99	gold quality
pleura	UBERON:0000977	87.93	gold quality
orbitofrontal cortex	UBERON:0004167	87.92	gold quality
parietal pleura	UBERON:0002400	87.86	gold quality
nephron tubule	UBERON:0001231	87.84	silver quality
lower lobe of lung	UBERON:0008949	87.66	gold quality
occipital lobe	UBERON:0002021	87.58	gold quality
adrenal gland	UBERON:0002369	87.51	gold quality
germinal epithelium of ovary	UBERON:0001304	87.50	gold quality
prefrontal cortex	UBERON:0000451	87.49	gold quality
mucosa of stomach	UBERON:0001199	87.38	gold quality
urinary bladder	UBERON:0001255	87.29	gold quality
endocervix	UBERON:0000458	87.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.25	gold quality
spleen	UBERON:0002106	87.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.13	gold quality
lower esophagus	UBERON:0013473	87.08	gold quality
popliteal artery	UBERON:0002250	87.04	gold quality
right coronary artery	UBERON:0001625	87.02	gold quality
tibial artery	UBERON:0007610	87.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.96	gold quality
cortex of kidney	UBERON:0001225	86.82	gold quality
frontal cortex	UBERON:0001870	86.81	gold quality
vermiform appendix	UBERON:0001154	86.80	gold quality
calcaneal tendon	UBERON:0003701	86.75	gold quality
cerebellum	UBERON:0002037	86.62	gold quality
left ovary	UBERON:0002119	86.57	gold quality
upper leg skin	UBERON:0004262	86.51	gold quality
cerebellar cortex	UBERON:0002129	86.35	gold quality
cerebellar hemisphere	UBERON:0002245	86.34	gold quality
tibia	UBERON:0000979	86.32	gold quality
tonsil	UBERON:0002372	86.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.28	gold quality
left coronary artery	UBERON:0001626	86.26	gold quality
tibial nerve	UBERON:0001323	86.16	gold quality
right ovary	UBERON:0002118	86.16	gold quality
right lobe of thyroid gland	UBERON:0001119	86.06	gold quality
aorta	UBERON:0000947	86.05	gold quality
caput epididymis	UBERON:0004358	86.03	gold quality
descending thoracic aorta	UBERON:0002345	86.01	gold quality
coronary artery	UBERON:0001621	86.00	gold quality
cauda epididymis	UBERON:0004360	85.92	gold quality
leukocyte	CL:0000738	85.88	gold quality
thoracic mammary gland	UBERON:0005200	85.84	gold quality
neocortex	UBERON:0001950	85.82	gold quality
mammary gland	UBERON:0001911	85.76	gold quality
substantia nigra pars compacta	UBERON:0001965	85.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.70	gold quality
apex of heart	UBERON:0002098	85.69	gold quality
kidney epithelium	UBERON:0004819	85.69	gold quality
heart right ventricle	UBERON:0002080	85.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.53	gold quality
ovary	UBERON:0000992	85.48	gold quality
cerebellar vermis	UBERON:0004720	85.48	gold quality
epididymis	UBERON:0001301	85.46	gold quality
body of uterus	UBERON:0009853	85.43	gold quality
paraflocculus	UBERON:0005351	85.40	gold quality
metanephros cortex	UBERON:0010533	85.39	gold quality
frontal pole	UBERON:0002795	85.33	gold quality
epithelium of mammary gland	UBERON:0003244	85.33	gold quality
mammary duct	UBERON:0001765	85.27	gold quality
small intestine	UBERON:0002108	85.25	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.24	gold quality
mononuclear cell	CL:0000842	85.21	gold quality
caecum	UBERON:0001153	85.21	gold quality
monocyte	CL:0000576	85.20	gold quality
middle frontal gyrus	UBERON:0002702	85.18	gold quality
hypothalamus	UBERON:0001898	85.17	gold quality
inferior olivary complex	UBERON:0002127	85.12	gold quality
right lung	UBERON:0002167	85.08	gold quality
colonic epithelium	UBERON:0000397	85.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.14

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	41.6
Locus coeruleus	tissue	40.0
Postcentral gyrus	tissue	36.1
Hippocampus	tissue	30.3	not detected
Corpus callosum	tissue	28.0
Cerebral cortex	tissue	26.6	low
Somatosensory cortex	tissue	26.6
Substantia nigra	tissue	26.4
Putamen	tissue	25.7
Thalamus	tissue	25.7
Ventral forebrain	tissue	25.2
Hypothalamus	tissue	24.8
Pons	tissue	24.6
Basal ganglia	tissue	24.6	not detected
Superior colliculi	tissue	24.2
Midbrain	tissue	24.1
Occipital cortex	tissue	23.9
Hippocampal formation	tissue	23.8
Entorhinal cortex	tissue	23.8
Prefrontal cortex	tissue	23.7
Cerebellum	tissue	23.7	low
Motor cortex	tissue	23.5
Septum	tissue	23.1
Insular cortex	tissue	23.0
Medulla oblongata	tissue	22.6
Retrosplenial cortex	tissue	22.4
Lymph node	tissue	22.3	not detected
Retrosplenial and cingulate cortex	tissue	21.9
Temporal cortex	tissue	21.8
Amygdala	tissue	21.6
Olfactory bulb	tissue	21.4
Periaqueductal gray	tissue	20.9
Spinal cord	tissue	20.4
Caudate putamen	tissue	20.4
Parathyroid gland	tissue	19.1	not detected
Spleen	tissue	18.9	not detected
Choroid plexus	tissue	16.5
Ovary	tissue	16.2	low
Frontal cortex	tissue	14.7
Tonsil	tissue	14.7	not detected
Thyroid gland	tissue	14.5	medium
Fallopian tube	tissue	14.4	not detected
Thymus	tissue	13.9
Adrenal gland	tissue	13.5	low
Appendix	tissue	12.9	not detected
Seminal vesicle	tissue	12.6	not detected
Small intestine	tissue	12.4	high
Salivary gland	tissue	12.2	not detected
Lung	tissue	12.2	not detected
Cervix	tissue	11.1	not detected
Pituitary gland	tissue	10.7
Pancreas	tissue	10.2	not detected
Heart muscle	tissue	10.1	not detected
Kidney	tissue	10.1	not detected
Breast	tissue	9.3	low
Gallbladder	tissue	9.2	low
Urinary bladder	tissue	9.1	not detected
Bone marrow	tissue	9.1	not detected
Stomach 1	tissue	9.0	not detected
Esophagus	tissue	9.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Claustrum (46.1), Parieto-temporal junction (white matter) (45.1), Paraventricular nucleus (44.7), Dorsomedial nucleus (44.0), Nucleus ambiguus (43.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting JADE2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 198 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.25, missense Z 3.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000681547 splits into 9 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:134,535,858–134,538,034	47 / 42.2	1.11	no
5:134,538,035–134,559,830	44 / 92.0	0.48	no
5:134,559,831–134,559,979	78 / 64.9	1.20	no
5:134,559,980–134,566,172	129 / 255.4	0.51	no
5:134,566,173–134,566,254	39 / 37.6	1.04	no
5:134,566,255–134,566,579	88 / 140.6	0.63	no
5:134,566,580–134,573,682	2 / 18.6	0.11	yes (p 1.2e-04)
5:134,573,683–134,578,677	119 / 163.9	0.73	no
5:134,578,678–134,579,314	300 / 300.7	1.00	no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	jade2	ENSDARG00000053389
mus_musculus	Jade2	ENSMUSG00000020387
rattus_norvegicus	Jade2	ENSRNOG00000004956
drosophila_melanogaster	Br140	FBGN0033155
caenorhabditis_elegans		WBGENE00003034
caenorhabditis_elegans		WBGENE00021810

Paralogs (8): JADE1 (ENSG00000077684), MLLT10 (ENSG00000078403), BRPF3 (ENSG00000096070), BRD1 (ENSG00000100425), JADE3 (ENSG00000102221), PHF14 (ENSG00000106443), BRPF1 (ENSG00000156983), MLLT6 (ENSG00000275023)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1924151) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 16 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
abnormal sternum morphology	1
small spleen	1
reduced long-term potentiation	1
impaired synaptic plasticity	1
abnormal seminal vesicle morphology	1
abnormal excitatory postsynaptic potential	1
abnormal synaptic transmission	1
abnormal long-term spatial reference memory	1
decreased prepulse inhibition	1
decreased bone mineral content	1
enlarged urinary bladder	1
decreased fasting circulating glucose level	1
impaired long-term object recognition memory	1
decreased miniature excitatory postsynaptic current frequency	1
decreased dendritic spine density	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Pongo abelii	Q5RD88	99.3%	Diamond
Bos taurus	Q5E9T7	98.4%	Diamond
Xenopus laevis	Q6GQJ2	77.2%	Diamond
Arabidopsis thaliana	Q8GZ42	75.3%	Diamond
Drosophila pseudoobscura pseudoobscura	Q29EQ3	70.1%	Diamond
Xenopus tropicalis	Q0P4S5	66.8%	Diamond
Oryza sativa Japonica Group	Q6K431	59.0%	Diamond
Saccharomyces cerevisiae S288C	Q12311	45.0%	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
LINC02999	ncRNA	102546229
JADE2-AS1	ncRNA	124901070
SEC24A	protein-coding	10802
SAR1B	protein-coding	51128
LINC01843	ncRNA	101927934

Protein

Protein identifiers

E3 ubiquitin-protein ligase Jade-2 — Q9NQC1 (reviewed: Q9NQC1)

Alternative names: Jade family PHD finger protein 2, PHD finger protein 15

All UniProt accessions (10): A0A087X085, A0A0C4DFT8, A0A7P0T8T0, A0A7P0TAP8, A0A7P0Z4H4, B5MBX1, C9J929, Q9NQC1, G3XAA4, H7C0P2

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. Acts as an E3 ubiquitin-protein ligase mediating the ubiquitination and subsequent proteasomal degradation of target protein histone demethylase KDM1A. Also acts as a ubiquitin ligase E3 toward itself. Positive regulator of neurogenesis.

Subunit / interactions. Component of the HBO1 complex composed at least of ING4 or ING5, MYST2/HBO1, MEAF6, and one of JADE1, JADE2 and JADE3. Interacts (via C-terminus) with KDM1A (via AOD/Tower domain).

Domain organisation. The first PHD domain is essential for its E3 ubiquitin ligase activity.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the JADE family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQC1-1	1	yes
Q9NQC1-2	2
Q9NQC1-3	3

RefSeq proteins (23): NP_001276913, NP_001276914, NP_001295072, NP_001375114, NP_001375115, NP_001375116, NP_001375117, NP_001424843, NP_001424844, NP_001424845, NP_001424846, NP_001424849, NP_001424850, NP_001424851, NP_001424852, NP_001424853, NP_001424854, NP_001424855, NP_001424856, NP_001424857, NP_001424858, NP_001424859, NP_056103 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019542	Enhancer_polycomb-like_N	Domain
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR034732	EPHD	Domain
IPR039548	JADE2_PHD	Domain
IPR039549	JADE2_ePHD	Domain
IPR050701	Histone_Mod_Regulator	Family

Pfam: PF10513, PF13831, PF13832

UniProt features (26 total): compositionally biased region 6, modified residue 6, region of interest 4, zinc finger region 3, splice variant 2, mutagenesis site 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQC1-F1	62.79	0.22

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH uncertain · IF enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6)

Type	Positions
Phosphoserine	9, 15, 117
N6-acetyllysine	32, 38, 298

Mutagenesis-validated functional residues (2)

Position	Phenotype
202	loss of e3 ubiquitin-protein ligase activity on kdm1a.
243	loss of e3 ubiquitin-protein ligase activity on kdm1a.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-3214847	HATs acetylate histones	curated
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—

MSigDB gene sets: 404 (showing top): E2F_Q4, E2F_Q4_01, RRAGTTGT_UNKNOWN, FREAC2_01, PAX4_01, TGCGCANK_UNKNOWN, E2F4DP1_01, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, AAGTCCA_MIR422B_MIR422A, CMYB_01, TTTGTAG_MIR520D, SP3_Q3, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_GROWTH, MODULE_493

GO Biological Process (6): regulation of DNA replication (GO:0006275), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), protein ubiquitination (GO:0016567), regulation of cell cycle (GO:0051726), regulation of DNA biosynthetic process (GO:2000278)

GO Molecular Function (10): zinc ion binding (GO:0008270), histone H4K5 acetyltransferase activity (GO:0043995), histone H4K8 acetyltransferase activity (GO:0043996), histone H4K12 acetyltransferase activity (GO:0043997), ubiquitin protein ligase activity (GO:0061630), histone reader activity (GO:0140566), protein binding (GO:0005515), transferase activity (GO:0016740), histone H3K14 acetyltransferase activity (GO:0036408), metal ion binding (GO:0046872)

GO Cellular Component (4): histone acetyltransferase complex (GO:0000123), nucleus (GO:0005634), nucleoplasm (GO:0005654), extracellular exosome (GO:0070062)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

27 GO namespaces:

Category	Terms
histone H4 acetyltransferase activity	3
regulation of DNA metabolic process	2
DNA replication	1
chromatin organization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
protein modification by small protein conjugation	1
cell cycle	1
regulation of cellular process	1
regulation of macromolecule biosynthetic process	1
DNA biosynthetic process	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleosome	1
histone binding	1
chromatin-protein adaptor activity	1
binding	1
catalytic activity	1
histone H3 acetyltransferase activity	1
cation binding	1
chromatin	1
protein acetyltransferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
regulation of DNA biosynthetic process	BP	direct assay
regulation of DNA replication	BP	direct assay
regulation of cell cycle	BP	direct assay
extracellular exosome	CC	high-throughput assay
histone acetyltransferase complex	CC	direct assay
nucleoplasm	CC	direct assay
histone H4K12 acetyltransferase activity	MF	direct assay
histone H4K5 acetyltransferase activity	MF	direct assay
histone H4K8 acetyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 534 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JADE2	SETD1A	O15047	737
JADE2	MEAF6	Q9HAF1	509
JADE2	KAT7	O95251	499
JADE2	CCDC198	Q9NVL8	489
JADE2	USP28	Q96RU2	425
JADE2	SAYSD1	Q9NPB0	413
JADE2	ING4	Q9UNL4	410
JADE2	ZNF512	Q96ME7	384
JADE2	CEBPG	P53567	366
JADE2	OR10G6	Q8NH81	363
JADE2	SAR1B	Q9Y6B6	361
JADE2	KDM1A	O60341	351
JADE2	DYDC2	Q96IM9	349
JADE2	ING5	Q8WYH8	346
JADE2	ELOA	Q14241	344

IntAct

Human interaction partners of JADE2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
ING5	physical association	0.740	3
ING4	physical association	0.660	1
ZBTB3	physical association	0.370	1
ZBTB5	physical association	0.370	1
ZNF496	physical association	0.370	1
PACSIN1	physical association	0.000	2
TTC3	physical association	0.000	1

BioGRID (104 interactions; top human partners by supporting records): ING5 (Two-hybrid; 10 records), ING4 (Affinity Capture-MS; 9 records), KAT7 (Affinity Capture-MS; 7 records), MEAF6 (Affinity Capture-MS; 7 records), ING3 (Affinity Capture-MS; 4 records), AARSD1 (Affinity Capture-MS; 3 records), C14orf80 (Affinity Capture-MS; 3 records), CCDC88A (Affinity Capture-MS; 3 records), CCDC93 (Affinity Capture-MS; 3 records), MYO5C (Affinity Capture-MS; 3 records), MYO9A (Affinity Capture-MS; 3 records), PIK3C3 (Affinity Capture-MS; 3 records), PIK3R4 (Affinity Capture-MS; 3 records), MEN1 (Affinity Capture-MS; 2 records), ASH2L (Affinity Capture-MS)

Protein complexes (CORUM) (2)

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

2 complexes by size:

Complex	Subunits	Members
ING4 complex (ING4, JADE2, KAT7, MEAF6)	4	ING4, JADE2, KAT7, MEAF6
ING5 complex (ING5, JADE2, KAT7, MEAF6)	4	ING5, JADE2, KAT7, MEAF6

Disease & clinical

Genetic variants

Variant evidence for JADE2: 103 ClinVar records (0 pathogenic / likely pathogenic); 45 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	5
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 884):

Position(s)	Effect	Δscore	Sites
5:134537987–134537988	acceptor_loss	1.0000	5
5:134538084–134538085	donor_loss	1.0000	5
5:134552050–134552051	acceptor_loss	1.0000	6
5:134559829	acceptor_loss	1.0000
5:134559991–134559992	donor_loss	1.0000	4
5:134560743	acceptor_gain	1.0000
5:134560744–134560745	acceptor_loss	1.0000	6
5:134560958–134560959	donor_loss	1.0000	5
5:134564492–134564493	acceptor_loss	1.0000	6
5:134564611–134564612	donor_loss	1.0000	4

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.44e-07
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.000561
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000714

Disease associations

OMIM: gene MIM:610515 | disease phenotypes:

GWAS associations

showing 30 of 45 associations:

Study	Trait	p-value
GCST004616_69	Platelet distribution width	6e-22
GCST002541_17	Menarche (age at onset)	3e-20
GCST010702_168	Subcortical volume (MOSTest)	7e-19
GCST008363_43	Offspring birth weight	3e-17
GCST90002394_390	Monocyte percentage of white cells	3e-15
GCST009597_38	Multiple sclerosis	2e-13
GCST010988_312	Adult body size	9e-12
GCST010703_265	Brain morphology (MOSTest)	3e-11
GCST009524_100	Household income (MTAG)	7e-11
GCST008362_180	Birth weight	8e-11
GCST90002398_246	Neutrophil count	8e-11
GCST000880_41	Menarche (age at onset)	2e-10
GCST90002393_659	Monocyte count	8e-10
GCST010796_3121	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-9
GCST010796_4617	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-9
GCST010796_4618	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-9
GCST90002407_310	White blood cell count	2e-9
GCST004894_130	Type 2 diabetes	3e-9
GCST008550_1	Mental health study participation (completed survey)	4e-9
GCST009379_344	Type 2 diabetes	4e-9
GCST010796_3122	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-9
GCST010796_3120	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-9
GCST010796_4616	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-9
GCST008550_3	Mental health study participation (completed survey)	8e-9
GCST010796_3119	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-9
GCST008550_22	Mental health study participation (completed survey)	9e-9
GCST010796_3117	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST010796_3123	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST005830_4	Hand grip strength	2e-8
GCST008550_2	Mental health study participation (completed survey)	2e-8

EFO canonical traits (from GWAS)

16 canonical traits:

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0009101	age at first birth measurement
EFO:0007984	platelet component distribution width
EFO:0004340	body mass index
EFO:0006941	grip strength measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0006781	coffee consumption measurement
EFO:0010130	health study participation
EFO:0009695	household income
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0004319	smoking cessation
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
trichostatin A	decreases expression, affects expression	3
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
monomethylarsonous acid	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	affects phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
pentanal	decreases expression	1
3-deazaneplanocin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
scriptaid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	decreases expression	1
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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