KDM3B

Summary

KDM3B (lysine demethylase 3B, HGNC:1337) is a protein-coding gene on chromosome 5q31.2, encoding Lysine-specific demethylase 3B (Q7LBC6). Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.

Predicted to enable chromatin DNA binding activity; histone H3K9 demethylase activity; and transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of acute lymphoblastic leukemia; breast cancer; colorectal cancer; and lung non-small cell carcinoma.

Source: NCBI Gene 51780 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 505 total — 24 pathogenic, 21 likely-pathogenic (top 7% of genes corpus-wide)
• Regional missense constraint (gnomAD): 8 of 19 regions constrained (≈22% of expected missense variation)
• GTEx eGene: eQTL in 24 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 34
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.12 (highly constrained)
• MANE Select transcript: NM_016604

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1337
Approved symbol	KDM3B
Name	lysine demethylase 3B
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1082, NET22
Ensembl gene	ENSG00000120733
Ensembl biotype	protein_coding
OMIM	609373
Entrez	51780

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000314358

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

ENST00000314358, ENST00000504095, ENST00000505756, ENST00000507996, ENST00000508386, ENST00000509468, ENST00000510866, ENST00000512928, ENST00000882287, ENST00000882288, ENST00000882289, ENST00000938918, ENST00000938919, ENST00000938920, ENST00000938921, ENST00000938922, ENST00000959876, ENST00001126777, ENST00001132851

RefSeq mRNA: 1 — MANE Select: NM_016604 NM_016604

CCDS: CCDS34242

Canonical transcript exons

ENST00000314358 — 24 exons

Exon	Start	End
ENSE00000973553	138352685	138352987
ENSE00001195239	138372674	138372841
ENSE00001295170	138435620	138437027
ENSE00001309552	138381516	138381590
ENSE00001348759	138386022	138386621
ENSE00003460880	138431425	138431559
ENSE00003481345	138429826	138429965
ENSE00003505193	138391013	138392261
ENSE00003512048	138393171	138393372
ENSE00003515931	138430249	138430425
ENSE00003526737	138427189	138427319
ENSE00003526791	138399860	138400012
ENSE00003542312	138427967	138428086
ENSE00003582952	138417483	138417610
ENSE00003590982	138379584	138379708
ENSE00003591670	138426975	138427065
ENSE00003612438	138377720	138377825
ENSE00003613395	138425411	138425582
ENSE00003619129	138375093	138375206
ENSE00003631024	138415132	138415239
ENSE00003649799	138418953	138419232
ENSE00003665595	138398178	138398392
ENSE00003683042	138420706	138420962
ENSE00003692804	138424075	138424341

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0876 / max 208.2473, expressed in 1755 samples.

Highest expression (Bgee): ventricular zone, ganglionic eminence, gluteal muscle, embryo, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

KDM3B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 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 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	1.6e-14	-0.52	5:138453830:G:C
Muscle Skeletal	eqtl	2.9e-07	+0.11	5:138443230:G:T
Adipose Subcutaneous	eqtl	8.7e-07	+0.11	5:138443292:A:C
Adipose Visceral Omentum	eqtl	1.1e-06	+0.14	5:138448565:C:T
Artery Tibial	eqtl	1.3e-06	+0.08	5:138439584:G:A
Skin Sun Exposed Lower leg	eqtl	7.6e-05	+0.08	5:138443292:A:C
Lung	eqtl	2.0e-04	+0.10	5:138448565:C:T
Thyroid	eqtl	2.5e-04	+0.08	5:138453285:C:A
Esophagus Mucosa	eqtl	3.5e-04	+0.09	5:138453285:C:A
Breast Mammary Tissue	eqtl	3.7e-04	+0.11	5:138353523:G:A
Brain Cerebellar Hemisphere	sqtl	4.4e-04	-0.48	5:138453285:C:A
Whole Blood	eqtl	5.3e-04	-0.18	5:138369941:C:T
Nerve Tibial	eqtl	1.2e-03	-0.09	5:138451296:CT:C
Artery Aorta	sqtl	1.3e-03	+0.37	5:138439584:G:A
Brain Caudate basal ganglia	eqtl	1.3e-03	+0.17	5:138324519:G:C
Pancreas	eqtl	1.9e-03	+0.15	5:138151652:TA:T
Esophagus Gastroesophageal Junction	eqtl	1.9e-03	+0.09	5:138453285:C:A
Brain Frontal Cortex BA9	eqtl	2.7e-03	+0.16	5:138362610:C:T
Ovary	eqtl	6.0e-03	+0.53	5:138595059:T:C
Skin Sun Exposed Lower leg	sqtl	7.2e-03	-1.09	5:138711851:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
58756	10.0402	1755
58760	0.0475	18

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.50	gold quality
ganglionic eminence	UBERON:0004023	95.63	gold quality
gluteal muscle	UBERON:0002000	95.07	gold quality
embryo	UBERON:0000922	94.91	gold quality
monocyte	CL:0000576	93.63	gold quality
mononuclear cell	CL:0000842	93.57	gold quality
leukocyte	CL:0000738	93.51	gold quality
caput epididymis	UBERON:0004358	93.48	gold quality
mucosa of stomach	UBERON:0001199	93.35	gold quality
ileal mucosa	UBERON:0000331	93.27	gold quality
gastrocnemius	UBERON:0001388	93.24	gold quality
muscle of leg	UBERON:0001383	93.05	gold quality
tibialis anterior	UBERON:0001385	92.95	gold quality
saphenous vein	UBERON:0007318	92.79	gold quality
right uterine tube	UBERON:0001302	92.59	gold quality
urethra	UBERON:0000057	92.57	gold quality
synovial joint	UBERON:0002217	92.56	gold quality
cortical plate	UBERON:0005343	92.56	gold quality
corpus epididymis	UBERON:0004359	92.45	gold quality
bone marrow cell	CL:0002092	92.42	gold quality
bronchus	UBERON:0002185	92.23	gold quality
mammary duct	UBERON:0001765	92.21	gold quality
epithelium of bronchus	UBERON:0002031	92.21	gold quality
blood	UBERON:0000178	92.16	gold quality
popliteal artery	UBERON:0002250	92.14	gold quality
tibial artery	UBERON:0007610	92.14	gold quality
right coronary artery	UBERON:0001625	92.13	gold quality
cardia of stomach	UBERON:0001162	92.12	gold quality
right ovary	UBERON:0002118	91.98	gold quality
nipple	UBERON:0002030	91.96	gold quality
muscle organ	UBERON:0001630	91.93	gold quality
skeletal muscle organ	UBERON:0014892	91.93	gold quality
artery	UBERON:0001637	91.88	gold quality
nasal cavity mucosa	UBERON:0001826	91.88	gold quality
parotid gland	UBERON:0001831	91.88	gold quality
skin of leg	UBERON:0001511	91.87	gold quality
bronchial epithelial cell	CL:0002328	91.85	gold quality
triceps brachii	UBERON:0001509	91.82	gold quality
left ovary	UBERON:0002119	91.80	gold quality
colonic epithelium	UBERON:0000397	91.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.73	gold quality
rectum	UBERON:0001052	91.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.70	gold quality
epithelium of mammary gland	UBERON:0003244	91.69	gold quality
periodontal ligament	UBERON:0008266	91.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.58	gold quality
choroid plexus epithelium	UBERON:0003911	91.53	gold quality
deltoid	UBERON:0001476	91.50	gold quality
nasal cavity epithelium	UBERON:0005384	91.48	gold quality
ovary	UBERON:0000992	91.41	gold quality
corpus callosum	UBERON:0002336	91.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.34	gold quality
skin of abdomen	UBERON:0001416	91.33	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.33	gold quality
lower esophagus	UBERON:0013473	91.32	gold quality
superior surface of tongue	UBERON:0007371	91.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.30	gold quality
left uterine tube	UBERON:0001303	91.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.22	gold quality
cauda epididymis	UBERON:0004360	91.18	gold quality
right lung	UBERON:0002167	91.17	gold quality
inferior olivary complex	UBERON:0002127	91.13	gold quality
renal medulla	UBERON:0000362	91.07	gold quality
lymph node	UBERON:0000029	91.06	gold quality
aorta	UBERON:0000947	91.04	gold quality
transverse colon	UBERON:0001157	90.99	gold quality
islet of Langerhans	UBERON:0000006	90.97	gold quality
zone of skin	UBERON:0000014	90.95	gold quality
small intestine	UBERON:0002108	90.91	gold quality
descending thoracic aorta	UBERON:0002345	90.90	gold quality
penis	UBERON:0000989	90.89	gold quality
bone marrow	UBERON:0002371	90.84	gold quality
spleen	UBERON:0002106	90.82	gold quality
seminal vesicle	UBERON:0000998	90.75	gold quality
urinary bladder	UBERON:0001255	90.75	gold quality
skin of hip	UBERON:0001554	90.75	gold quality
fundus of stomach	UBERON:0001160	90.72	gold quality
upper leg skin	UBERON:0004262	90.72	gold quality
colon	UBERON:0001155	90.71	gold quality
granulocyte	CL:0000094	90.67	gold quality
intestine	UBERON:0000160	90.65	gold quality
trigeminal ganglion	UBERON:0001675	90.64	gold quality
saliva-secreting gland	UBERON:0001044	90.61	gold quality
trachea	UBERON:0003126	90.60	gold quality
body of uterus	UBERON:0009853	90.60	gold quality
sigmoid colon	UBERON:0001159	90.58	gold quality
stomach	UBERON:0000945	90.54	gold quality
large intestine	UBERON:0000059	90.52	gold quality
muscle tissue	UBERON:0002385	90.51	gold quality
skeletal muscle tissue	UBERON:0001134	90.49	gold quality
minor salivary gland	UBERON:0001830	90.48	gold quality
tonsil	UBERON:0002372	90.48	gold quality
tongue	UBERON:0001723	90.43	gold quality
medulla oblongata	UBERON:0001896	90.42	gold quality
body of stomach	UBERON:0001161	90.37	gold quality
pharyngeal mucosa	UBERON:0000355	90.34	gold quality
calcaneal tendon	UBERON:0003701	90.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.47

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	33.9	high
Choroid plexus	tissue	33.9
Hippocampus	tissue	33.9	high
Retina	tissue	33.6
Nucleus accumbens	tissue	33.5
Thymus	tissue	33.4
Parathyroid gland	tissue	32.2	high
Cerebellum	tissue	31.0	high
Corpus callosum	tissue	29.5
Postcentral gyrus	tissue	29.1
Locus coeruleus	tissue	28.8
Spinal cord	tissue	28.6
Midbrain	tissue	28.4
Tonsil	tissue	27.5	high
Superior colliculi	tissue	27.3
Substantia nigra	tissue	26.9
Epididymis	tissue	26.7	high
Skin 1	tissue	26.5	high
Thalamus	tissue	26.5
Hippocampal formation	tissue	25.9
Ovary	tissue	25.8	high
Hypothalamus	tissue	25.6
Tongue	tissue	25.3
Medulla oblongata	tissue	25.1
Ventral forebrain	tissue	25.0
Periaqueductal gray	tissue	24.9
Olfactory bulb	tissue	24.6
Septum	tissue	24.5
Prefrontal cortex	tissue	24.4
Cerebral cortex	tissue	24.4	high
Pons	tissue	24.4
Seminal vesicle	tissue	24.4	high
Somatosensory cortex	tissue	24.3
Basal ganglia	tissue	23.9	high
Bone marrow	tissue	23.9	high
Breast	tissue	23.7	high
Putamen	tissue	23.7
Motor cortex	tissue	23.6
Entorhinal cortex	tissue	23.5
Amygdala	tissue	23.3
Spleen	tissue	23.2	high
Occipital cortex	tissue	22.9
Insular cortex	tissue	22.9
Fallopian tube	tissue	22.8	high
Rectum	tissue	22.5	high
Temporal cortex	tissue	22.5
Retrosplenial cortex	tissue	22.2
Retrosplenial and cingulate cortex	tissue	21.8
Thyroid gland	tissue	21.7	high
Lymph node	tissue	21.5	high
Cervix	tissue	21.3	high
Colon	tissue	20.6	high
Prostate	tissue	20.4	high
Endometrium 1	tissue	20.1	medium
Kidney	tissue	20.0	high
Stomach 1	tissue	19.6	high
Smooth muscle	tissue	19.4	medium
Placenta	tissue	19.2	high
Vagina	tissue	19.1	medium
Heart muscle	tissue	18.5	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (40.3), Area postrema (39.2), Medial geniculate body (38.2), Periaquaductal grey, anterior (37.9), Periaquaductal grey, dorsal (37.4).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
PPARA	Activation
UCP1	Activation

miRNA regulators (miRDB)

Targeting KDM3B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 160 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6783-3P	99.89	67.92	2059

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.117, missense Z 6.23 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000314358 splits into 19 regions with different missense tolerance; 8 are missense-constrained (≈22% 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
5:138,352,796–138,352,984	99 / 97.5	1.02	no
5:138,352,985–138,372,787	16 / 48.6	0.33	yes (p 2.9e-06)
5:138,372,788–138,386,080	166 / 216.4	0.77	no
5:138,386,081–138,386,127	4 / 20.8	0.19	yes (p 2.3e-04)
5:138,386,128–138,391,063	205 / 227.6	0.90	no
5:138,391,064–138,391,141	10 / 29.3	0.34	yes (p 3.6e-04)
5:138,391,142–138,391,916	294 / 311.7	0.94	no
5:138,391,917–138,392,255	84 / 135.8	0.62	no
5:138,392,256–138,399,888	76 / 190.2	0.40	no
5:138,399,889–138,399,983	2 / 42.6	0.05	yes (p 4.9e-10)
5:138,399,984–138,417,506	44 / 71.1	0.62	no
5:138,417,507–138,417,548	1 / 18.8	0.05	yes (p 4.1e-05)
5:138,417,549–138,418,967	14 / 32.5	0.43	no
5:138,418,968–138,419,165	87 / 83.3	1.04	no
5:138,419,166–138,420,714	10 / 29.1	0.34	yes (p 4.1e-04)
5:138,420,715–138,424,243	137 / 166.9	0.82	no
5:138,424,244–138,427,261	66 / 178.8	0.37	no
5:138,427,262–138,427,316	0 / 23.7	0.00	yes (p 1.1e-06)
5:138,427,317–138,435,697	79 / 270.5	0.29	yes (p 2.5e-31)

Literature-anchored findings (GeneRIF, showing 12)

• A novel nuclear protein, 5qNCA is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31. (PMID:11687974)
• evidence that the H3K9-me1/2 demethylase KDM3B might play a role in leukemogenesis via activation of lmo2 through interdependent actions with the histone acetyltransferase complex containing CBP (PMID:22615488)
• High expression of KDM3B and KDM5A is associated with a better prognosis (no recurrence after mastectomy p=0.005 and response to docetaxel p=0.005)in breast cancer patients. (PMID:23266085)
• H3K9 demethylase KDM3B represses transcription of the angiogenesis regulatory gene, ANGPT1. (PMID:25413303)
• we found that KDM3B exhibits potential tumor-suppressive activity and transcriptionally modulates HOXA1 expression via RARE in AML. (PMID:28540746)
• The results implicate KDM3B as a crucial epigenetic factor in cell cycle regulation that manipulates chromatin dynamics and transcription in hepatocarcinoma. (PMID:30514438)
• pathogenic variants in KDM3B cause a syndrome characterized by intellectual disability, short stature, and facial dysmorphism (PMID:30929739)
• Systematic characterization of chromatin modifying enzymes identifies KDM3B as a critical regulator in castration resistant prostate cancer. (PMID:31822799)
• JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability. (PMID:32070414)
• Histone demethylase KDM3B protects against ferroptosis by upregulating SLC7A11. (PMID:32107878)
• Histone lysine demethylase 3B (KDM3B) regulates the propagation of autophagy via transcriptional activation of autophagy-related genes. (PMID:32716961)
• Unraveling the Role of JMJD1B in Genome Stability and the Malignancy of Melanomas. (PMID:39409021)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm3b	ENSDARG00000062267
mus_musculus	Kdm3b	ENSMUSG00000038773
rattus_norvegicus	Kdm3b	ENSRNOG00000050200
drosophila_melanogaster	Kdm3	FBGN0037703

Paralogs (3): KDM3A (ENSG00000115548), HR (ENSG00000168453), JMJD1C (ENSG00000171988)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923356) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sternum morphology	1
abnormal oocyte morphology	1
decreased body length	1
decreased body weight	1
decreased body size	1
decreased locomotor activity	1
decreased exploration in new environment	1
impaired embryo implantation	1
postnatal growth retardation	1
hemorrhage	1
female infertility	1
abnormal skin morphology	1
increased mean corpuscular volume	1
decreased ovulation rate	1
abnormal female reproductive system physiology	1
abnormal facial morphology	1
abnormal decidualization	1
decreased circulating insulin-like growth factor I level	1
decreased circulating estradiol level	1
decreased survivor rate	1
prolonged estrous cycle	1
prolonged diestrus	1
decreased prepulse inhibition	1
decreased fertilization frequency	1
abnormal pregnancy	1

+2 more (showing top 25).

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
Xenopus laevis	Q5HZN1	89.4%	Diamond
Arabidopsis thaliana	C0SUU8	71.9%	Diamond
Gallus gallus	Q5ZIX8	69.6%	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
KIF20A	protein-coding	10112
GFRA3	protein-coding	2676
FAM53C	protein-coding	51307
CDC23	protein-coding	8697
CDC25C	protein-coding	995
EGR1	protein-coding	1958
REEP2	protein-coding	51308

Protein

Protein identifiers

Lysine-specific demethylase 3B — Q7LBC6 (reviewed: Q7LBC6)

Alternative names: JmjC domain-containing histone demethylation protein 2B, Jumonji domain-containing protein 1B, Nuclear protein 5qNCA, [histone H3]-dimethyl-L-lysine(9) demethylase 3B

All UniProt accessions (3): H0Y946, H0Y9V5, Q7LBC6

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Highly expressed in placenta, skeletal muscle, kidney, heart and liver.

Disease relevance. Diets-Jongmans syndrome (DIJOS) [MIM:618846] An autosomal dominant disorder characterized by varying degrees of intellectual disability, developmental delay, short stature, and characteristic facial features such as a wide mouth, a pointed chin, long ears and a low columella. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Domain organisation. Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.

Miscellaneous. Its gene is located in the 5q region of the genome which is deleted in del(5q) interstitial deletion, a frequent deletion found in myeloid leukemias and myelodysplasias, suggesting that it may be a good candidate for the del(5q) tumor suppressor gene.

Similarity. Belongs to the JHDM2 histone demethylase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7LBC6-1	1	yes
Q7LBC6-2	2
Q7LBC6-3	3

RefSeq proteins (1): NP_057688* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR045109	LSDs-like	Family
IPR054294	KDM3A/B_DUF7030	Domain
IPR054503	KDM3AB_Tudor	Domain
IPR054504	PWWP_KDM3B	Domain

Pfam: PF02373, PF22987, PF22988, PF22989

Enzyme classification (BRENDA)

• EC 1.14.11.65 — [histone H3]-dimethyl-L-lysine9 demethylase (BRENDA: 9 organisms, 67 substrates, 84 inhibitors, 4 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[HISTONE H3]-N6,N6-DIMETHYL-L-LYSINE9	0.106–0.1061	2
[HISTONE H3]-N6-METHYL-L-LYSINE9	0.095–0.0952	2

Catalyzed reactions (Rhea)

• N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:60188)

UniProt features (99 total): helix 22, sequence variant 16, strand 16, modified residue 14, compositionally biased region 8, region of interest 7, binding site 3, splice variant 3, turn 3, initiator methionine 1, chain 1, short sequence motif 1, domain 1, zinc finger region 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 36 structures by resolution:

PDB	Title	Method	Resolution (Å)
5R7X	PanDDA analysis group deposition of ground-state model of Human JMJD1B	X-RAY DIFFRACTION	1.44
5RAR	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with TD000005c	X-RAY DIFFRACTION	1.47
5RB5	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM010010a	X-RAY DIFFRACTION	1.51
5RAB	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001726a	X-RAY DIFFRACTION	1.52
5RAG	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001767a	X-RAY DIFFRACTION	1.52
5RB2	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001784a	X-RAY DIFFRACTION	1.52
5RB3	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with XS039249d	X-RAY DIFFRACTION	1.53
5RAI	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with XS040404c	X-RAY DIFFRACTION	1.54
5RAW	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM009970a	X-RAY DIFFRACTION	1.55
5RB4	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001677a	X-RAY DIFFRACTION	1.55
5RAA	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM009990a	X-RAY DIFFRACTION	1.57
5RB7	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001648a	X-RAY DIFFRACTION	1.57
5RAS	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with XS036302b	X-RAY DIFFRACTION	1.58
5RAO	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001084a	X-RAY DIFFRACTION	1.59
5RAJ	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with BD009815a	X-RAY DIFFRACTION	1.61
5RAF	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001559a	X-RAY DIFFRACTION	1.62
5RAY	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001469a	X-RAY DIFFRACTION	1.63
5RB6	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001569a	X-RAY DIFFRACTION	1.63
5RAH	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM010032a	X-RAY DIFFRACTION	1.66
5RAL	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with XS039332c	X-RAY DIFFRACTION	1.68
5RAK	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with XS040486b	X-RAY DIFFRACTION	1.69
5RAC	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001810a	X-RAY DIFFRACTION	1.73
5RAU	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with DA000165b	X-RAY DIFFRACTION	1.73
5RB1	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001700a	X-RAY DIFFRACTION	1.76
5RAV	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001763a	X-RAY DIFFRACTION	1.77
5RAZ	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM010013a	X-RAY DIFFRACTION	1.81
5RAQ	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001577a	X-RAY DIFFRACTION	1.85
5RAE	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001558a	X-RAY DIFFRACTION	1.88
5RAD	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM001568a	X-RAY DIFFRACTION	1.9
5RAP	PanDDA analysis group deposition – Crystal Structure of JMJD1B in complex with FM000707a	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7LBC6-F1	59.78	0.25

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; golgi apparatus

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

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

Ligand- & substrate-binding residues (3)

Position	Role
1560	Fe cation
1562	Fe cation
1689	Fe cation

Post-translational modifications (15)

Type	Positions
N-acetylalanine	2
N6-acetyllysine	361
Phosphoserine	492, 546, 556, 560, 766, 773, 778, 779, 798, 1253, 1259
Phosphothreonine	614
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	788

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-3214842	HDMs demethylate histones	curated
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—

MSigDB gene sets: 322 (showing top): RNGTGGGC_UNKNOWN, GCM_MAP4K4, GCM_GSPT1, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, RORA1_01, MORF_ATRX, GGGTGGRR_PAX4_03, GCM_BCL2L1, MORF_RAF1, MORF_FANCG, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX1_UP, GCM_NUMA1, AACTTT_UNKNOWN, CAIRO_HEPATOBLASTOMA_UP

GO Biological Process (4): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (8): transcription coregulator activity (GO:0003712), zinc ion binding (GO:0008270), chromatin DNA binding (GO:0031490), histone H3K9 demethylase activity (GO:0032454), histone H3K9me/H3K9me2 demethylase activity (GO:0140683), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (4): histone deacetylase complex (GO:0000118), chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

23 GO namespaces:

Category	Terms
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cellular component organization	1
chromatin organization	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
chromatin binding	1
histone H3 demethylase activity	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H3K9 demethylase activity	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
chromosome	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,374 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM3B	KDM4A	O75164	737
KDM3B	KDM4B	O94953	623
KDM3B	KDM5C	P41229	609
KDM3B	KDM4C	Q9H3R0	598
KDM3B	KDM7A	Q6ZMT4	597
KDM3B	H3-3A	P06351	594
KDM3B	H3C1	P02295	594
KDM3B	H3-4	Q16695	594
KDM3B	H3-7	Q5TEC6	594
KDM3B	H3-5	Q6NXT2	594
KDM3B	H3C14	Q71DI3	594
KDM3B	KDM2B	Q8NHM5	564
KDM3B	KDM2A	Q9Y2K7	559
KDM3B	KDM5B	Q9UGL1	557
KDM3B	EHMT2	Q96KQ7	556

IntAct

Human interaction partners of KDM3B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
SPAG8	physical association	0.370	1
ZNF512B	physical association	0.370	1
CPNE3	association	0.350	1
LMNB2	association	0.350	1

BioGRID (136 interactions; top human partners by supporting records): RFPL4B (Affinity Capture-MS; 3 records), RNF41 (Two-hybrid; 3 records), ALOX5 (Affinity Capture-MS; 2 records), AR (Proximity Label-MS; 2 records), BRD4 (Affinity Capture-MS; 2 records), CPN1 (Affinity Capture-MS; 2 records), MRPL38 (Affinity Capture-MS; 2 records), MYC (Proximity Label-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PLOD1 (Affinity Capture-MS; 2 records), SERPINB2 (Affinity Capture-MS; 2 records), SMYD3 (Affinity Capture-MS; 2 records), TH (Affinity Capture-MS; 2 records), TIPARP (Affinity Capture-MS; 2 records), TOPBP1 (Proximity Label-MS; 2 records)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
KDM3B	“up-regulates quantity by expression”	PPARA	“transcriptional regulation”
KDM3B	“up-regulates quantity by expression”	UCP1	“transcriptional regulation”
KDM3B	“down-regulates activity”	H3C1	demethylation
KDM3B	“down-regulates activity”	H3-4	demethylation
KDM3B	“down-regulates activity”	H3-3A	demethylation
2-oxoglutarate(2-)	“up-regulates activity”	KDM3B	“chemical activation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — MBL, PAST.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for KDM3B: 505 ClinVar records (45 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	21
Uncertain significance	309
Likely benign	82
Benign	16

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 45 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2505249	NM_016604.4(KDM3B):c.4631A>G (p.Tyr1544Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1700099	NM_016604.4(KDM3B):c.4414C>T (p.Arg1472Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1685359	NM_016604.4(KDM3B):c.4627G>A (p.Ala1543Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
971547	NM_016604.4(KDM3B):c.607del (p.Val203fs)	Pathogenic	criteria provided, single submitter	1
1320806	NM_016604.4(KDM3B):c.4622A>G (p.Tyr1541Cys)	Pathogenic	criteria provided, single submitter	1
1326846	NM_016604.4(KDM3B):c.4206G>A (p.Trp1402Ter)	Pathogenic	criteria provided, single submitter	1
1678202	NM_016604.4(KDM3B):c.3431C>G (p.Ser1144Ter)	Pathogenic	criteria provided, single submitter	1
1700100	NM_016604.4(KDM3B):c.3046C>T (p.Gln1016Ter)	Pathogenic	criteria provided, single submitter	1
1701906	NM_016604.4(KDM3B):c.331C>T (p.Arg111Ter)	Pathogenic	criteria provided, single submitter	1
2828011	NM_016604.4(KDM3B):c.4504T>C (p.Phe1502Leu)	Pathogenic	criteria provided, single submitter	1
3378038	NM_016604.4(KDM3B):c.2845C>T (p.Arg949Ter)	Pathogenic	criteria provided, single submitter	1
3391504	NM_016604.4(KDM3B):c.4981C>T (p.Arg1661Ter)	Pathogenic	criteria provided, single submitter	1
3767662	NM_016604.4(KDM3B):c.4888C>T (p.Arg1630Ter)	Pathogenic	criteria provided, single submitter	1
3769805	NM_016604.4(KDM3B):c.2827C>T (p.Arg943Trp)	Pathogenic	criteria provided, single submitter	1
3863427	NM_016604.4(KDM3B):c.2144del (p.Pro715fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore KDM3B’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,928):

Position(s)	Effect	Δscore	Sites
5:138372672–138372673	acceptor_loss	1.0000	4
5:138372842–138372843	donor_loss	1.0000	5
5:138375207–138375208	donor_loss	1.0000	5
5:138377710	acceptor_gain	1.0000
5:138377716	acceptor_gain	1.0000
5:138377718–138377719	acceptor_loss	1.0000	4
5:138377826–138377827	donor_loss	1.0000	5
5:138393163	acceptor_gain	1.0000
5:138393168	acceptor_gain	1.0000
5:138393169–138393170	acceptor_loss	1.0000	5

AlphaMissense

4,936 missense substitutions predicted likely pathogenic (of 11,512 scored), across 994 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
M1540	9	0.987	1.000
M1497	9	0.974	0.998
M1498	9	0.959	1.000
M1030	9	0.956	0.997
M1570	9	0.955	1.000
M1506	9	0.949	0.996
M1094	9	0.884	0.995
M1481	9	0.881	0.996
D1487	8	1.000	1.000
D1565	8	1.000	1.000
D1732	8	1.000	1.000
D1032	8	0.999	1.000
H1042	8	0.999	1.000
H1112	8	0.999	1.000
D1444	8	0.999	1.000
F1462	8	0.999	1.000
D1493	8	0.999	1.000
F1494	8	0.999	1.000
H1560	8	0.999	1.000
D1645	8	0.999	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.78e-07
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000116

Disease associations

OMIM: gene MIM:609373 | disease phenotypes: MIM:618846

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Diets-Jongmans syndrome	Definitive	Autosomal dominant	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Childhood solid tumours	green
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Monogenic hearing loss	amber
Monogenic short stature	amber
Paediatric disorders	amber

Mondo (3): Diets-Jongmans syndrome (MONDO:0030012), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258)

Orphanet (3): Rare genetic epilepsy (Orphanet:183512), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

34 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000307	Pointed chin
HP:0000365	Hearing impairment
HP:0000455	Broad nasal tip
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000776	Congenital diaphragmatic hernia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001537	Umbilical hernia
HP:0001561	Polyhydramnios
HP:0001623	Breech presentation
HP:0001629	Ventricular septal defect
HP:0002171	Gliosis
HP:0002247	Duodenal atresia
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0007074	Thick corpus callosum
HP:0008872	Feeding difficulties in infancy
HP:0009765	Low hanging columella
HP:0011671	Interrupted inferior vena cava with azygous continuation
HP:0030853	Heterotaxy
HP:0031936	Delayed ability to walk
HP:0400004	Long ear

GWAS associations

11 associations:

Study	Trait	p-value
GCST002541_18	Menarche (age at onset)	9e-14
GCST009600_63	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	2e-9
GCST002539_68	Schizophrenia	5e-9
GCST004521_25	Autism spectrum disorder or schizophrenia	1e-8
GCST003582_1	Response to radiotherapy in prostate cancer (toxicity, urinary frequency)	4e-8
GCST012465_63	Bipolar disorder	4e-8
GCST000880_31	Menarche (age at onset)	5e-8
GCST006990_1	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	7e-8
GCST008115_28	Bipolar I disorder	2e-7
GCST008103_59	Bipolar disorder	8e-7
GCST002818_1	HIV-1 susceptibility	3e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0000180	HIV-1 infection
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0009963	bipolar I disorder

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3784906 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Histone demethylases

Binding affinities (BindingDB)

19 measured of 33 human assays (33 total across all organisms); most potent 19 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4303308	IC50	1.7 nM
GSKJ1	IC50	2.8 nM
CHEMBL3183531	IC50	4.2 nM
CHEMBL5193187	KD	130 nM
CHEMBL4849961	IC50	681 nM
CHEMBL5091848	IC50	4000 nM
CHEMBL5173150	KD	7790 nM
CHEMBL5072902	IC50	7800 nM
CHEMBL5071002	IC50	10500 nM
CHEMBL5089117	IC50	15300 nM
CHEMBL5083418	IC50	15900 nM
CHEMBL5191875	KD	16300 nM
CHEMBL5089880	IC50	19200 nM
CHEMBL5081435	IC50	19400 nM
CHEMBL5076580	IC50	20200 nM
CHEMBL5084638	IC50	23800 nM
CHEMBL5070745	IC50	29800 nM
CHEMBL5071515	IC50	30100 nM
CHEMBL5084143	IC50	86600 nM

ChEMBL bioactivities

3 potent at pChembl≥5 of 15 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.89	Kd	130	nM	CHEMBL5193187
5.16	IC50	6900	nM	CHEMBL3183531
5.11	Kd	7790	nM	CHEMBL5173150

PubChem BioAssay actives

3 with measured affinity, of 39 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[4-[[(3S,3aR,6S,6aR)-3-[(4-phenylpyrimidin-2-yl)amino]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]sulfamoyl]phenyl]acetamide	1872454: Binding affinity to CM7 sensor chip immobilized full-length KDM3B (unknown origin) expressed in Sf9 insect cells assessed as dissociation constant incubated for 60 secs by SPR analysis	kd	0.1300	uM
ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate	2145036: Inhibition of KDM3B (842 to 1761 residues)(unknown origin) by Alphalisa assay	ic50	6.9000	uM
N-[4-[[(3S,3aR,6S,6aR)-3-[[4-(3-tert-butylphenyl)pyrimidin-2-yl]amino]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]sulfamoyl]phenyl]acetamide	1872454: Binding affinity to CM7 sensor chip immobilized full-length KDM3B (unknown origin) expressed in Sf9 insect cells assessed as dissociation constant incubated for 60 secs by SPR analysis	kd	7.7900	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
trichostatin A	affects expression	1
arsenite	decreases reaction, affects binding	1
manganese chloride	decreases expression, increases abundance	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Nitric Oxide	increases expression	1
Rotenone	decreases expression	1
Thiram	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3789208	Binding	Inhibition of recombinant KDM3B (842 to 1761 residues) (unknown origin) expressed in baculovirus infected sf9 cells using biotin-H3K9me as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by AlphaLisa	Recent Progress in Histone Demethylase Inhibitors. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU24	HAP1 KDM3B (-) 1	Cancer cell line	Male
CVCL_SU25	HAP1 KDM3B (-) 2	Cancer cell line	Male
CVCL_SU26	HAP1 KDM3B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 210 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
NCT03770832	Not specified	ACTIVE_NOT_RECRUITING	Wearable Sensors and Video Recordings to Monitor Motor Development
NCT03830879	Not specified	RECRUITING	Shenzhen Birth Cohort Study
NCT03835689	Not specified	COMPLETED	Strongest FamiliesTM Neurodevelopmental
NCT03882788	Not specified	COMPLETED	The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
NCT03922087	Not specified	COMPLETED	No-worry Baby Project
NCT03977259	Not specified	ACTIVE_NOT_RECRUITING	Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
NCT04043572	Not specified	UNKNOWN	The Biomarkers of Neurological Disease in Utero Study
NCT04096430	Not specified	RECRUITING	Evaluation of Effectiveness of Child-oriented Goal-setting in Paediatric Rehabilitation (the ENGAGE Approach)
NCT04108273	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children
NCT04201509	Not specified	COMPLETED	Validity of Neurocognitive Assessment Methods in Childhood ADHD
NCT04233775	Not specified	UNKNOWN	Altered Cerebral Growth and Development in Infants With Congenital Heart Disease
NCT04313283	Not specified	COMPLETED	Translating Peer-to-Peer Support Into a Clinical Setting

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for KDM3B across ~30M SureChEMBL compounds — explore on Sugi Predict.