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 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 467 total — 24 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• 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: 17 — 10 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

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

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.

FANTOM5 promoters (2 alternative TSS)

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

Top tissues by expression

300 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
PPARA	Activation
UCP1	Activation

miRNA regulators (miRDB)

160 targeting KDM3B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

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)

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): Q7LBC6, H0Y946, H0Y9V5

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), 1 shown:

• 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 (97 total): helix 20, 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)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5R7X	X-RAY DIFFRACTION	1.44
5RAR	X-RAY DIFFRACTION	1.47
5RB5	X-RAY DIFFRACTION	1.51
5RAB	X-RAY DIFFRACTION	1.52
5RAG	X-RAY DIFFRACTION	1.52
5RB2	X-RAY DIFFRACTION	1.52
5RB3	X-RAY DIFFRACTION	1.53
5RAI	X-RAY DIFFRACTION	1.54
5RAW	X-RAY DIFFRACTION	1.55
5RB4	X-RAY DIFFRACTION	1.55
5RAA	X-RAY DIFFRACTION	1.57
5RB7	X-RAY DIFFRACTION	1.57
5RAS	X-RAY DIFFRACTION	1.58
5RAO	X-RAY DIFFRACTION	1.59
5RAJ	X-RAY DIFFRACTION	1.61
5RAF	X-RAY DIFFRACTION	1.62
5RAY	X-RAY DIFFRACTION	1.63
5RB6	X-RAY DIFFRACTION	1.63
5RAH	X-RAY DIFFRACTION	1.66
5RAL	X-RAY DIFFRACTION	1.68
5RAK	X-RAY DIFFRACTION	1.69
5RAC	X-RAY DIFFRACTION	1.73
5RAU	X-RAY DIFFRACTION	1.73
5RB1	X-RAY DIFFRACTION	1.76
5RAV	X-RAY DIFFRACTION	1.77
5RAZ	X-RAY DIFFRACTION	1.81
5RAQ	X-RAY DIFFRACTION	1.85
5RAE	X-RAY DIFFRACTION	1.88
5RAD	X-RAY DIFFRACTION	1.9
5RAP	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

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

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): 1560; 1562; 1689

Post-translational modifications (15): 2, 361, 492, 546, 556, 560, 614, 766, 773, 778, 779, 798, 1253, 1259, 788

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
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 (3): 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

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
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

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM3B	YTHDC1	Q96MU7	956
KDM3B	KDM4B	O94953	714
KDM3B	KDM4A	O75164	702
KDM3B	KDM4C	Q9H3R0	634
KDM3B	KDM5C	P41229	614
KDM3B	KDM2B	Q8NHM5	611
KDM3B	KDM5B	Q9UGL1	604
KDM3B	KDM7A	Q6ZMT4	600
KDM3B	KDM2A	Q9Y2K7	587
KDM3B	KDM4D	Q6B0I6	579
KDM3B	KDM1A	O60341	561
KDM3B	PHF8	Q9UPP1	558
KDM3B	KDM8	Q8N371	552
KDM3B	KDM6B	O15054	545
KDM3B	EHMT2	Q96KQ7	544

IntAct

77 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
ALOX5	DDHD2	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
CPN1	CEP170	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
ZNF512B	KDM3B	psi-mi:“MI:0915”(physical association)	0.370
SPAG8	KDM3B	psi-mi:“MI:0915”(physical association)	0.370
KDM3B	LMNB2	psi-mi:“MI:0914”(association)	0.350
AK1	NBAS	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
RFPL4B	KRBA1	psi-mi:“MI:0914”(association)	0.350
PLOD1	COL25A1	psi-mi:“MI:0914”(association)	0.350
TRIM11	BTN3A3	psi-mi:“MI:0914”(association)	0.350
SERPINB2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
TH	MAP3K7	psi-mi:“MI:0914”(association)	0.350
SMYD3	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
USP18	NME1	psi-mi:“MI:0914”(association)	0.350
KDM3B	CPNE3	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
CLNS1A	EPB41	psi-mi:“MI:0914”(association)	0.350
NUCKS1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): KDM3B (Affinity Capture-RNA), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Synthetic Lethality), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), DEPDC1 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), KDM3B (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IYX6, A0A1L8H0H2, A5X7A0, A7XYJ6, E1BE02, F6NSX9, F8VPJ6, O35914, O57415, P37275, P59598, P59759, Q03172, Q13029, Q2KHR2, Q3UH06, Q5EXX3, Q5R7F2, Q5ZIE8, Q5ZLR2, Q62947, Q63755, Q64318, Q6NRM0, Q6ZPY7, Q76L83, Q7LBC6, Q7YR76, Q80VX4, Q86V15, Q8BHZ4, Q8BLG0, Q8BRH4, Q8BX22, Q8BZ32, Q8C0C0, Q8IZQ8, Q8NEZ4, Q8R5I7, Q8VIM5

Diamond homologs: C0SUU8, C0SV12, F4HZD1, Q15652, Q5HZN1, Q5ZIX8, Q63679, Q6IRB8, Q6PCM1, Q6ZPY7, Q7LBC6, Q8H1S7, Q8VYB9, Q9SSE9, Q9VHC5, Q9Y4C1, Q69ZK6, P97609

SIGNOR signaling

6 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”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases activate PKNs	5	19.1×	4e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	11.2×	4e-03
mRNA Polyadenylation	7	7.4×	7e-03
mRNA Splicing - Major Pathway	9	5.9×	4e-03
Dengue Virus-Host Interactions	9	5.0×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription by RNA polymerase III	5	48.3×	4e-05

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	19
Uncertain significance	282
Likely benign	73
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1320806	NM_016604.4(KDM3B):c.4622A>G (p.Tyr1541Cys)	Pathogenic
1326846	NM_016604.4(KDM3B):c.4206G>A (p.Trp1402Ter)	Pathogenic
1678202	NM_016604.4(KDM3B):c.3431C>G (p.Ser1144Ter)	Pathogenic
1700100	NM_016604.4(KDM3B):c.3046C>T (p.Gln1016Ter)	Pathogenic
1701906	NM_016604.4(KDM3B):c.331C>T (p.Arg111Ter)	Pathogenic
2505249	NM_016604.4(KDM3B):c.4631A>G (p.Tyr1544Cys)	Pathogenic
2828011	NM_016604.4(KDM3B):c.4504T>C (p.Phe1502Leu)	Pathogenic
3378038	NM_016604.4(KDM3B):c.2845C>T (p.Arg949Ter)	Pathogenic
3391504	NM_016604.4(KDM3B):c.4981C>T (p.Arg1661Ter)	Pathogenic
3767662	NM_016604.4(KDM3B):c.4888C>T (p.Arg1630Ter)	Pathogenic
3769805	NM_016604.4(KDM3B):c.2827C>T (p.Arg943Trp)	Pathogenic
3863427	NM_016604.4(KDM3B):c.2144del (p.Pro715fs)	Pathogenic
3897596	NM_016604.4(KDM3B):c.1448dup (p.Leu483fs)	Pathogenic
4042250	NM_016604.4(KDM3B):c.3749_3750del (p.Glu1250fs)	Pathogenic
4042251	NM_016604.4(KDM3B):c.4606dup (p.Leu1536fs)	Pathogenic
4281327	NM_016604.4(KDM3B):c.3256C>T (p.Gln1086Ter)	Pathogenic
4819831	NM_016604.4(KDM3B):c.2409del (p.Leu804fs)	Pathogenic
864849	NM_016604.4(KDM3B):c.277G>T (p.Glu93Ter)	Pathogenic
864850	NM_016604.4(KDM3B):c.1007A>G (p.Asp336Gly)	Pathogenic
864851	NM_016604.4(KDM3B):c.5191G>A (p.Glu1731Lys)	Pathogenic
864852	NM_016604.4(KDM3B):c.3095A>T (p.Asp1032Val)	Pathogenic
864853	NM_016604.4(KDM3B):c.133C>T (p.Arg45Ter)	Pathogenic
971547	NM_016604.4(KDM3B):c.607del (p.Val203fs)	Pathogenic
976703	NM_016604.4(KDM3B):c.2828G>A (p.Arg943Gln)	Pathogenic
1334599	NM_016604.4(KDM3B):c.3082C>T (p.Arg1028Trp)	Likely pathogenic
1685359	NM_016604.4(KDM3B):c.4627G>A (p.Ala1543Thr)	Likely pathogenic
1706594	NM_016604.4(KDM3B):c.427C>T (p.Arg143Ter)	Likely pathogenic
1803986	NM_016604.4(KDM3B):c.2743_2745del (p.Arg915del)	Likely pathogenic
2203773	NM_016604.4(KDM3B):c.5070+1G>A	Likely pathogenic
2429967	NM_016604.4(KDM3B):c.3047-1G>A	Likely pathogenic

SpliceAI

3405 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138372672:A:AG	acceptor_gain	1.0000
5:138372673:G:GA	acceptor_gain	1.0000
5:138372673:GA:G	acceptor_gain	1.0000
5:138372673:GAT:G	acceptor_gain	1.0000
5:138372673:GATC:G	acceptor_gain	1.0000
5:138372673:GATCT:G	acceptor_gain	1.0000
5:138372838:CCTG:C	donor_gain	1.0000
5:138372839:CTG:C	donor_gain	1.0000
5:138372841:GGTG:G	donor_loss	1.0000
5:138372842:G:C	donor_loss	1.0000
5:138372842:G:GG	donor_gain	1.0000
5:138375091:A:AG	acceptor_gain	1.0000
5:138375092:G:GG	acceptor_gain	1.0000
5:138375092:GACTT:G	acceptor_gain	1.0000
5:138375202:TTCAG:T	donor_loss	1.0000
5:138375203:TCAG:T	donor_loss	1.0000
5:138375204:CAGGT:C	donor_loss	1.0000
5:138375205:AG:A	donor_loss	1.0000
5:138375206:GGT:G	donor_loss	1.0000
5:138375207:G:A	donor_loss	1.0000
5:138375208:T:A	donor_loss	1.0000
5:138377709:A:AG	acceptor_gain	1.0000
5:138377710:T:G	acceptor_gain	1.0000
5:138377715:A:AG	acceptor_gain	1.0000
5:138377716:C:G	acceptor_gain	1.0000
5:138377716:CCAGA:C	acceptor_loss	1.0000
5:138377717:CAGA:C	acceptor_gain	1.0000
5:138377717:CAGAT:C	acceptor_loss	1.0000
5:138377718:A:AG	acceptor_gain	1.0000
5:138377718:AGAT:A	acceptor_gain	1.0000

AlphaMissense

11512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138379611:T:A	V203D	1.000
5:138393186:T:C	L882P	1.000
5:138393213:T:C	L891P	1.000
5:138393233:T:C	F898L	1.000
5:138393234:T:C	F898S	1.000
5:138393234:T:G	F898C	1.000
5:138393235:C:A	F898L	1.000
5:138393235:C:G	F898L	1.000
5:138393241:G:C	Q900H	1.000
5:138393241:G:T	Q900H	1.000
5:138393251:T:A	C904S	1.000
5:138393251:T:C	C904R	1.000
5:138393252:G:A	C904Y	1.000
5:138393252:G:C	C904S	1.000
5:138393252:G:T	C904F	1.000
5:138393253:C:G	C904W	1.000
5:138393273:T:C	L911P	1.000
5:138393278:A:G	K913E	1.000
5:138393280:G:C	K913N	1.000
5:138393280:G:T	K913N	1.000
5:138393281:T:A	C914S	1.000
5:138393281:T:C	C914R	1.000
5:138393282:G:A	C914Y	1.000
5:138393282:G:C	C914S	1.000
5:138393282:G:T	C914F	1.000
5:138393283:T:G	C914W	1.000
5:138393284:C:A	R915S	1.000
5:138393287:G:A	E916K	1.000
5:138393290:T:A	C917S	1.000
5:138393290:T:C	C917R	1.000

dbSNP variants (sampled 300 via entrez): RS1000011653 (5:138388938 T>G), RS1000014593 (5:138359358 C>A,T), RS1000018624 (5:138388888 A>G), RS1000040982 (5:138394060 T>G), RS1000073473 (5:138373077 G>A), RS1000100134 (5:138382216 G>A), RS1000113786 (5:138431001 C>T), RS1000177127 (5:138409194 TAAA>T), RS1000210113 (5:138409520 G>A), RS1000226201 (5:138356296 A>G), RS1000265951 (5:138363513 T>A,C), RS1000287762 (5:138437319 G>C), RS1000296543 (5:138413334 G>C), RS1000353327 (5:138362889 C>T), RS1000384737 (5:138363183 C>G,T)

Disease associations

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

GenCC curated gene-disease

Disease	Classification	Inheritance
Diets-Jongmans syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (4): Diets-Jongmans syndrome (MONDO:0030012), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), syndromic intellectual disability (MONDO:0000508)

Orphanet (4): Rare genetic epilepsy (Orphanet:183512), Rare genetic intellectual disability (Orphanet:183757), Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

34 total (30 of 34 shown, 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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000880_31	Menarche (age at onset)	5.000000e-08
GCST002539_60	Schizophrenia	5.000000e-09
GCST002541_16	Menarche (age at onset)	9.000000e-14
GCST002818_1	HIV-1 susceptibility	3.000000e-06
GCST003582_1	Response to radiotherapy in prostate cancer (toxicity, urinary frequency)	4.000000e-08
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST006990_3	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	7.000000e-08
GCST008103_73	Bipolar disorder	8.000000e-07
GCST008115_23	Bipolar I disorder	2.000000e-07
GCST009600_88	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	2.000000e-09
GCST012465_63	Bipolar disorder	4.000000e-08

EFO canonical traits (4, from GWAS)

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)

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 (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.14.11.- Histone demethylases

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	affects expression, decreases expression, decreases methylation	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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	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	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	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	ACTIVE_NOT_RECRUITING	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