JMJD1C

Summary

JMJD1C (jumonji domain containing 1C, HGNC:12313) is a protein-coding gene on chromosome 10q21.3, encoding Jumonji domain-containing protein 1C (Q15652). Demethylates lysine in proteins, such as STAT3 or MDC1.

The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 221037 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 124
• Clinical variants (ClinVar): 1,611 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 131
• Druggable target: yes
• MANE Select transcript: NM_032776

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12313
Approved symbol	JMJD1C
Name	jumonji domain containing 1C
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761F0118, KIAA1380, FLJ14374, KDM3C
Ensembl gene	ENSG00000171988
Ensembl biotype	protein_coding
OMIM	604503
Entrez	221037

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding_CDS_not_defined, 3 protein_coding, 1 retained_intron

ENST00000327520, ENST00000399262, ENST00000402544, ENST00000467356, ENST00000469152, ENST00000483298, ENST00000489372, ENST00000490669, ENST00000497922, ENST00000542921, ENST00000633035

RefSeq mRNA: 7 — MANE Select: NM_032776 NM_001282948, NM_001318153, NM_001318154, NM_001322252, NM_001322254, NM_001322258, NM_032776

CCDS: CCDS41532, CCDS60538

Canonical transcript exons

ENST00000399262 — 26 exons

Exon	Start	End
ENSE00001895989	63465495	63465977
ENSE00003325710	63200476	63200677
ENSE00003480238	63177717	63177856
ENSE00003503198	63264651	63264764
ENSE00003518338	63176297	63176473
ENSE00003530653	63168435	63168566
ENSE00003538863	63198513	63198727
ENSE00003561094	63190894	63191108
ENSE00003568069	63184608	63184738
ENSE00003568913	63219878	63219983
ENSE00003580079	63193345	63193472
ENSE00003588543	63380318	63380482
ENSE00003588567	63183447	63183569
ENSE00003593690	63217207	63217331
ENSE00003609545	63215553	63215696
ENSE00003627681	63197411	63197563
ENSE00003632233	63185563	63185653
ENSE00003679917	63189168	63189446
ENSE00003683134	63194286	63194375
ENSE00003687317	63186215	63186383
ENSE00003693750	63192938	63193151
ENSE00003714117	63213473	63215151
ENSE00003724963	63215263	63215455
ENSE00003731370	63209063	63209235
ENSE00003736527	63206595	63208801
ENSE00003844054	63167225	63168134

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.9228 / max 2635.1744, expressed in 1822 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109677	28.4698	1714
109690	11.2599	1742
109678	11.2039	1446
109693	4.6952	1313
109673	3.7856	982
109683	2.2706	1063
109671	1.2416	527
109662	0.8494	410
109675	0.6355	301
109684	0.6307	351

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.75	gold quality
cerebellar hemisphere	UBERON:0002245	97.73	gold quality
cerebellar cortex	UBERON:0002129	97.61	gold quality
cortical plate	UBERON:0005343	97.59	gold quality
adrenal tissue	UBERON:0018303	96.71	gold quality
tendon	UBERON:0000043	96.70	gold quality
cerebellum	UBERON:0002037	96.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.32	gold quality
tendon of biceps brachii	UBERON:0008188	96.08	gold quality
jejunal mucosa	UBERON:0000399	95.82	gold quality
superficial temporal artery	UBERON:0001614	95.71	gold quality
trabecular bone tissue	UBERON:0002483	95.43	gold quality
ventricular zone	UBERON:0003053	95.18	gold quality
right lung	UBERON:0002167	95.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.11	gold quality
sperm	CL:0000019	95.08	gold quality
visceral pleura	UBERON:0002401	95.04	gold quality
tibia	UBERON:0000979	95.03	gold quality
ganglionic eminence	UBERON:0004023	94.77	gold quality
cartilage tissue	UBERON:0002418	94.66	gold quality
monocyte	CL:0000576	94.54	gold quality
mononuclear cell	CL:0000842	94.47	gold quality
leukocyte	CL:0000738	94.40	gold quality
left ovary	UBERON:0002119	94.38	gold quality
colonic epithelium	UBERON:0000397	94.32	gold quality
amniotic fluid	UBERON:0000173	94.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.15	gold quality
omental fat pad	UBERON:0010414	94.14	gold quality
peritoneum	UBERON:0002358	94.12	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	19.07
E-GEOD-130148	yes	4.49
E-MTAB-6075	no	2285.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD2, POU5F1

Literature-anchored findings (GeneRIF, showing 27)

• TRIP8 gene codes for a protein predicted to be a transcriptional regulator associated with nuclear thyroid hormone receptors. Positional candidate gene for autism. (PMID:17290275)
• the discovery of a new Receptors, Androgen coactivator which belongs to the JmjC containing enzyme family as a novel variant of JMJD1C (PMID:17353003)
• Human JMJD1C variant 2 with TRI8H1, TRI8H2, and JmjC domains showed 85.7% total-amino-acid identity with mouse Jmjd1c. (PMID:17549425)
• No evidence for JMJD1C histone demethylase activity towards H3K9. (PMID:23593242)
• JMJD1C regulates the RAP80-BRCA1 branch of this DNA-damage response (DDR) pathway. (PMID:24240613)
• JMJD1C represses neural differentiation of hESCs at least partially by epigenetically sustaining miR-302 expression (PMID:24318875)
• Depletion of JMJD1C impairs expansion and colony formation of leukemic cell lines, with the strongest effect observed in the MLL-rearranged ALL cell line SEM. (PMID:24501218)
• Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability. (PMID:26181491)
• genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). (PMID:26414697)
• JMJD1C is directly recruited by RUNX1-RUNX1T1 to its target genes and regulates their expression by maintaining low H3K9 dimethyl (H3K9me2) levels (PMID:26494788)
• Histone modifier genes (JMJD1C, RREB1, MINA, KDM7A) alter conotruncal heart phenotypes in 22q11.2 deletion syndrome. (PMID:26608785)
• JMJD1C is one of the target genes of hsa-miR-590- 3p. (PMID:27064872)
• Study provides evidence that SNPs of JMJD1C and KCNQ1 are prospectively associated with the risk of type 2 diabetes (T2D) in Korean population. Additionally, CDKAL1 may not be associated with T2D onset over the age of 40. (PMID:28406950)
• Polymorphisms in JMJD1C are associated with pubertal onset in boys and reproductive function in men (PMID:29222425)
• JMJD1C is the autosomal gene where variants have been demonstrated to be associated with Testosterone (one of Cardiovascular disease risk factors) at genome-wide significance. (PMID:29804699)
• High JMJD1C expression is associated with increased metabolic dysregulation and leukemogenesis. (PMID:30622285)
• Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures. (PMID:31954878)
• JMJD1C activates lipogenic gene transcription in liver.JMJD1C demethylates histone H3 K9 lysine at lipogenic promoters.JMJD1C is phosphorylated at the threonine T505 by mTOR. (PMID:32034158)
• JMJD1C knockdown affects myeloid cell lines proliferation, viability, and gemcitabine/carboplatin-sensitivity. (PMID:33075016)
• Finding underlying genetic mechanisms of two patients with autism spectrum disorder carrying familial apparently balanced chromosomal translocations. (PMID:33591602)
• AR-negative prostate cancer is vulnerable to loss of JMJD1C demethylase. (PMID:34475205)
• Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a. (PMID:34586733)
• JMJD1C-regulated lipid synthesis contributes to the maintenance of MLL-rearranged acute myeloid leukemia. (PMID:35468015)
• Histone demethylase KDM3C regulates the lncRNA GAS5-miR-495-3p-PHF8 axis in cardiac hypertrophy. (PMID:35777757)
• JMJD1C Regulates Megakaryopoiesis in In Vitro Models through the Actin Network. (PMID:36429088)
• Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity. (PMID:38356061)
• circ_JMJD1C expedites breast cancer progression by regulating miR-182-5p/JMJD1C/SOX4 axis. (PMID:38650133)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	jmjd1cb	ENSDARG00000079939
mus_musculus	Jmjd1c	ENSMUSG00000037876
rattus_norvegicus	Jmjd1c	ENSRNOG00000000648
drosophila_melanogaster	Kdm3	FBGN0037703

Paralogs (3): KDM3A (ENSG00000115548), KDM3B (ENSG00000120733), HR (ENSG00000168453)

Protein

Protein identifiers

Jumonji domain-containing protein 1C — Q15652 (reviewed: Q15652)

Alternative names: Thyroid receptor-interacting protein 8

All UniProt accessions (2): Q15652, H7BXU7

UniProt curated annotations — full annotation on UniProt →

Function. Demethylates lysine in proteins, such as STAT3 or MDC1. Demethylates MDC1, thereby promoting MDC1-RNF8 interaction and facilitating RNF8-dependent MDC1 ubiquitination essential for double-strand break (DSB) repair. Demethylation of STAT3 at ‘Lys-140’ facilitates its interactions with the phosphatase PTPN6 and restrains STAT3 activation. It is uncertain whether JMJD1C removes methyl groups from histone proteins as the other JMJD1/KDM3 proteins do. Nevertheless, JMJD1C may act as a context-specific histone demethylase. Implicated in lipogenic gene transcription in the liver, where USF1 recruits JMJD1C to lipogenic promoters in response to insulin or feeding stimuli, thereby potentially promoting H3K9me2 demethylation and enhancing chromatin accessibility. Post-translational modifications may regulate JMJD1C’s enzymatic activity, contributing to its context-specific functions. Alternatively, JMJD1C may influence chromatin regulation indirectly, acting as a scaffold or co-regulator that recruits or stabilizes other active demethylase complexes modifying histone marks. Plays an indispensable role in spermatogenesis. Coactivator of androgen receptor.

Subunit / interactions. Interacts with RNF8; promotes interaction between RNF8 and MDC1 through demethylation of MDC1.

Subcellular location. Nucleus Nucleus.

Post-translational modifications. Ubiquitinated. Protein abundance of JMJD1C is regulated by the ubiquitin proteasome pathway. Phosphorylated. Phosphorylation at Thr-505 by mTORC1 complex in response to insulin/feeding.

Activity regulation. Demethylase activity is regulated post-translationally via phosphorylation.

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

Similarity. Belongs to the JHDM2 histone demethylase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15652-1	1	yes
Q15652-2	2
Q15652-3	3, s-JMJD1C

RefSeq proteins (7): NP_001269877, NP_001305082, NP_001305083, NP_001309181, NP_001309183, NP_001309187, NP_116165* (*=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

UniProt features (104 total): modified residue 19, helix 17, compositionally biased region 14, strand 14, turn 7, sequence variant 7, region of interest 5, sequence conflict 5, splice variant 4, binding site 3, mutagenesis site 3, cross-link 2, chain 1, domain 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9GDK	X-RAY DIFFRACTION	1.78
5FZO	X-RAY DIFFRACTION	1.84
2YPD	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15652-F1	50.01	0.16

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): 2336; 2338; 2466

Post-translational modifications (21): 188, 317, 320, 373, 376, 475, 501, 505, 601, 604, 607, 617, 638, 639, 641, 652, 943, 1989, 2053, 2132 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
505	decreases of fatty acid synthase activity.
505	higher fatty acid synthase activity.
2336	no rescue effect on the impaired accumulation of conjugated ubiquitin proteins upon ir irradiation in jmjd1c-depleted ce

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis

MSigDB gene sets: 636 (showing top): WENDT_COHESIN_TARGETS_UP, GSE45365_NK_CELL_VS_CD8_TCELL_UP, ZHAN_MULTIPLE_MYELOMA_PR_DN, RORA1_01, TTTGTAG_MIR520D, AREB6_03, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, AP4_Q6, chr10q21, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, CACCAGC_MIR138, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, COUP_01

GO Biological Process (5): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), blood coagulation (GO:0007596), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (9): transcription coregulator activity (GO:0003712), zinc ion binding (GO:0008270), chromatin DNA binding (GO:0031490), histone H3K9 demethylase activity (GO:0032454), nuclear thyroid hormone receptor binding (GO:0046966), dioxygenase activity (GO:0051213), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

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-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
hemostasis	1
wound healing	1
coagulation	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
nuclear receptor binding	1
oxidoreductase activity	1
binding	1
catalytic activity	1
cation binding	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

1479 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JMJD1C	KDM4B	O94953	952
JMJD1C	REEP3	Q6NUK4	900
JMJD1C	KDM4A	O75164	893
JMJD1C	KDM4C	Q9H3R0	893
JMJD1C	KDM4D	Q6B0I6	879
JMJD1C	THRB	P10828	800
JMJD1C	KDM4E	B2RXH2	698
JMJD1C	KDM7A	Q6ZMT4	667
JMJD1C	BRD1	O95696	649
JMJD1C	BRPF1	P55201	633
JMJD1C	KDM4F	A0A1W2PPD8	624
JMJD1C	MDC1	Q14676	582
JMJD1C	PHF8	Q9UPP1	572
JMJD1C	DPF3	Q92784	561
JMJD1C	KMT2C	Q8NEZ4	548

IntAct

43 interactions, top by confidence:

A	B	Type	Score
JMJD1C	AR	psi-mi:“MI:0915”(physical association)	0.640
JMJD1C	AR	psi-mi:“MI:0407”(direct interaction)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
	JMJD1C	psi-mi:“MI:0915”(physical association)	0.400
JMJD1C	RNF8	psi-mi:“MI:0915”(physical association)	0.400
JMJD1C	SMC2	psi-mi:“MI:0915”(physical association)	0.400
JMJD1C	GADD45A	psi-mi:“MI:0915”(physical association)	0.370
NUDT21	JMJD1C	psi-mi:“MI:0915”(physical association)	0.370
JMJD1C	TK1	psi-mi:“MI:0915”(physical association)	0.370
JMJD1C	MT2A	psi-mi:“MI:0915”(physical association)	0.370
PSMC1	JMJD1C	psi-mi:“MI:0915”(physical association)	0.370
GATA3	PRMT5	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
NKX2-5		psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
H1-0	SMARCA5	psi-mi:“MI:0914”(association)	0.350
H2AZ1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
GOLGA2	ZNF609	psi-mi:“MI:2364”(proximity)	0.270
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
AR	SMARCC2	psi-mi:“MI:2364”(proximity)	0.270
AR	MED6	psi-mi:“MI:2364”(proximity)	0.270
RAVER1	KDM6A	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
KLF3	MCRIP1	psi-mi:“MI:2364”(proximity)	0.270
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270
SWSAP1	NACA	psi-mi:“MI:2364”(proximity)	0.270
TLK2	AQR	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (119): JMJD1C (Protein-peptide), JMJD1C (Biochemical Activity), JMJD1C (Affinity Capture-MS), JMJD1C (Proximity Label-MS), JMJD1C (Proximity Label-MS), JMJD1C (Proximity Label-MS), JMJD1C (Affinity Capture-RNA), JMJD1C (Affinity Capture-MS), JMJD1C (Affinity Capture-MS), JMJD1C (Affinity Capture-MS), JMJD1C (Affinity Capture-MS), JMJD1C (Proximity Label-MS), JMJD1C (Two-hybrid), JMJD1C (Proximity Label-MS), JMJD1C (Proximity Label-MS)

ESM2 similar proteins: A1YF22, A1YG99, A2T771, A2T7S4, B3DJM5, D3ZKB9, H2L008, O42410, O73590, P34303, P70121, Q03112, Q15652, Q15723, Q19418, Q21502, Q24478, Q2HNT1, Q2HNT2, Q2TB10, Q3UG20, Q58F21, Q5DTH5, Q5R7F2, Q5RCU4, Q61SK8, Q63HK5, Q66J63, Q69ZW3, Q6GN21, Q6P2L6, Q6ZSZ6, Q80VX4, Q86MI0, Q86T24, Q86UP3, Q8BN78, Q8C0C0, Q8CGV9, Q8IZD2

Diamond homologs: C0SUU8, C0SV12, F4HZD1, Q15652, Q5HZN1, Q5ZIX8, Q63679, Q6IRB8, Q6PCM1, Q6ZPY7, Q7LBC6, Q8H1S7, Q8VYB9, Q9SSE9, Q9VHC5, Q9Y4C1, Q69ZK6, O43593, P97609, Q61645

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
USF1	“up-regulates activity”	JMJD1C	binding
mTORC1	“up-regulates activity”	JMJD1C	phosphorylation
JMJD1C	“down-regulates activity”	H3-3A	demethylation
JMJD1C	“down-regulates activity”	H3-4	demethylation
JMJD1C	“down-regulates activity”	H3C1	demethylation
JMJD1C	“down-regulates activity”	“Histone H3”	demethylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Dengue Virus-Host Interactions	10	10.2×	1e-05
mRNA Splicing - Major Pathway	7	8.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1611 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	1009
Likely benign	481
Benign	55

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
804314	NM_032776.3(JMJD1C):c.326del (p.Pro109fs)	Pathogenic
804350	NM_032776.3(JMJD1C):c.3167_3207del (p.Ser1056fs)	Pathogenic
804311	NM_032776.3(JMJD1C):c.5863-6T>G	Likely pathogenic
804313	NM_032776.3(JMJD1C):c.1100T>C (p.Leu367Pro)	Likely pathogenic

SpliceAI

7271 predictions. Top by Δscore:

Variant	Effect	Δscore
10:63168428:CTCTT:C	donor_loss	1.0000
10:63168429:TCTTA:T	donor_loss	1.0000
10:63168430:CTTA:C	donor_loss	1.0000
10:63168431:TTA:T	donor_loss	1.0000
10:63168432:TACC:T	donor_loss	1.0000
10:63168433:A:AA	donor_loss	1.0000
10:63168434:C:A	donor_loss	1.0000
10:63176292:TATA:T	donor_loss	1.0000
10:63176293:ATACC:A	donor_loss	1.0000
10:63176294:TA:T	donor_loss	1.0000
10:63176296:CCT:C	donor_loss	1.0000
10:63176469:GAAAT:G	acceptor_gain	1.0000
10:63176470:AAAT:A	acceptor_gain	1.0000
10:63176471:AAT:A	acceptor_gain	1.0000
10:63176472:AT:A	acceptor_gain	1.0000
10:63176472:ATC:A	acceptor_loss	1.0000
10:63176474:C:CC	acceptor_gain	1.0000
10:63176474:CTGAA:C	acceptor_loss	1.0000
10:63176479:A:AC	acceptor_gain	1.0000
10:63176481:A:AC	acceptor_gain	1.0000
10:63176481:A:C	acceptor_gain	1.0000
10:63177709:A:AC	donor_gain	1.0000
10:63177710:C:CC	donor_gain	1.0000
10:63177711:TTATA:T	donor_loss	1.0000
10:63177713:ATAC:A	donor_gain	1.0000
10:63177731:C:A	donor_gain	1.0000
10:63177737:T:C	donor_gain	1.0000
10:63177752:T:A	donor_gain	1.0000
10:63177853:ATTC:A	acceptor_gain	1.0000
10:63177854:TTC:T	acceptor_gain	1.0000

AlphaMissense

16849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:63189400:A:T	I2113N	1.000
10:63190976:A:G	L2070P	1.000
10:63194349:A:G	C1891R	1.000
10:63197442:A:C	C1871W	1.000
10:63197444:A:G	C1871R	1.000
10:63197451:G:C	C1868W	1.000
10:63197453:A:G	C1868R	1.000
10:63197468:A:G	C1863R	1.000
10:63197475:G:C	C1860W	1.000
10:63197477:A:G	C1860R	1.000
10:63197483:A:G	W1858R	1.000
10:63197483:A:T	W1858R	1.000
10:63197517:A:C	C1846W	1.000
10:63197518:C:T	C1846Y	1.000
10:63197519:A:G	C1846R	1.000
10:63197552:A:G	W1835R	1.000
10:63197552:A:T	W1835R	1.000
10:63198645:A:G	W1787R	1.000
10:63198645:A:T	W1787R	1.000
10:63200496:A:C	C1752W	1.000
10:63200497:C:T	C1752Y	1.000
10:63200498:A:G	C1752R	1.000
10:63200552:A:G	C1734R	1.000
10:63200559:A:C	C1731W	1.000
10:63200561:A:G	C1731R	1.000
10:63200591:A:G	C1721R	1.000
10:63200629:A:G	L1708P	1.000
10:63206997:G:C	H1558D	1.000
10:63206998:T:A	R1557S	1.000
10:63206998:T:G	R1557S	1.000

dbSNP variants (sampled 300 via entrez): RS1000007107 (10:63327807 TAC>T), RS1000009011 (10:63404413 T>C), RS1000042409 (10:63402964 A>T), RS1000042686 (10:63427002 A>G), RS1000046046 (10:63226093 G>A,T), RS1000084992 (10:63294758 C>T), RS1000104266 (10:63233815 G>A,T), RS1000104638 (10:63266920 G>A), RS1000105409 (10:63342747 C>A,G), RS1000118349 (10:63448619 C>A), RS1000120495 (10:63382246 A>G,T), RS1000123810 (10:63506579 T>C), RS1000127918 (10:63270020 G>A), RS1000128987 (10:63414874 T>C), RS1000155920 (10:63184388 G>A)

Disease associations

OMIM: gene MIM:604503 | disease phenotypes: MIM:601764, MIM:616954

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Strong	Autosomal dominant
22q11.2 deletion syndrome	Supportive	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (8): neurodevelopmental disorder (MONDO:0700092), benign familial infantile epilepsy (MONDO:0017615), TELO2-related intellectual disability-neurodevelopmental disorder (MONDO:0014848), intellectual disability (MONDO:0001071), hepatoblastoma (MONDO:0018666), autism spectrum disorder (MONDO:0005258), complex neurodevelopmental disorder (MONDO:0100038), 22q11.2 deletion syndrome (MONDO:0018923)

Orphanet (5): Self-limited infantile epilepsy (Orphanet:306), TELO2-related intellectual disability-neurodevelopmental disorder (Orphanet:488642), Hepatoblastoma (Orphanet:449), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

131 total (30 of 131 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000113	Polycystic kidney dysplasia
HP:0000130	Abnormality of the uterus
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000389	Chronic otitis media
HP:0000396	Overfolded helix
HP:0000405	Conductive hearing impairment
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia

GWAS associations

124 associations (top):

Study	Trait	p-value
GCST000248_8	Liver enzyme levels	5.000000e-10
GCST000497_2	Mean platelet volume	3.000000e-21
GCST000693_14	Platelet aggregation	5.000000e-08
GCST000758_27	Triglycerides	3.000000e-12
GCST001276_14	Liver enzyme levels (alkaline phosphatase)	6.000000e-23
GCST001335_18	Mean platelet volume	2.000000e-44
GCST001337_30	Platelet count	2.000000e-24
GCST001417_1	Arthritis (juvenile idiopathic)	2.000000e-07
GCST001612_21	Sex hormone-binding globulin levels	6.000000e-35
GCST001612_29	Sex hormone-binding globulin levels	2.000000e-13
GCST001612_5	Sex hormone-binding globulin levels	1.000000e-25
GCST001653_2	Androgen levels	1.000000e-08
GCST001783_7	Platelet count	7.000000e-07
GCST002147_13	Fibrinogen	9.000000e-22
GCST002184_9	Mean platelet volume	3.000000e-18
GCST002186_1	Platelet count	2.000000e-06
GCST002216_30	Triglycerides	8.000000e-12
GCST002446_4	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	8.000000e-09
GCST002448_4	Plasma omega-6 polyunsaturated fatty acid levels (adrenic acid)	7.000000e-07
GCST002598_59	Educational attainment	1.000000e-06
GCST002897_18	Triglycerides	7.000000e-11
GCST003194_11	Fibrinogen levels	2.000000e-22
GCST003383_11	Platelet count	4.000000e-08
GCST003403_8	Vascular endothelial growth factor levels	3.000000e-19
GCST003680_5	C-reactive protein levels or HDL-cholesterol levels (pleiotropy)	2.000000e-08
GCST003831_48	Asthma	4.000000e-08
GCST003832_26	Asthma (childhood onset)	5.000000e-07
GCST004121_1	Fibrinogen levels	1.000000e-21
GCST004122_1	Fibrinogen levels	5.000000e-20
GCST004237_35	Triglyceride levels	3.000000e-19

EFO canonical traits (50, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0004530	triglyceride measurement
EFO:0004309	platelet count
EFO:0004696	sex hormone-binding globulin measurement
EFO:0004908	testosterone measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0004784	self reported educational attainment
EFO:0004458	C-reactive protein measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0007984	platelet component distribution width
EFO:0005090	basophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0004337	intelligence
EFO:0004570	bilirubin measurement
EFO:0008390	prothrombin time measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004312	vital capacity
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004531	urate measurement
EFO:0004750	interleukin 10 measurement
EFO:0004753	interleukin 12 measurement
EFO:0004810	interleukin-6 measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018197	Hepatoblastoma	C04.557.435.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3792271 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.3.1.48 Histone acetyltransferases (HATs)

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.72	IC50	1900	nM	CHEMBL3793278
5.57	Kd	2700	nM	CHEMBL5193187
5.09	Kd	8060	nM	CHEMBL5173150

PubChem BioAssay actives

3 with measured affinity, of 4 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
2-hydrazinylpyrimidine-4-carboxylic acid	1294309: Inhibition of KDM3C (unknown origin) using substrate peptide/ascorbate/2-OG/ Fe(2) as substrate preincubated for 15 mins followed by addition of substrate peptide/ ascorbate/2-OG/ Fe(2) measured after 1 hr by AlphaLISA method	ic50	1.9000	uM
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	1872453: Binding affinity to CM7 sensor chip immobilized partial-length JMJD1C (2274 to 2498 residues) (unknown origin) expressed in Escherichia coli assessed as dissociation constant incubated for 60 secs by SPR analysis	kd	2.7000	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	1872453: Binding affinity to CM7 sensor chip immobilized partial-length JMJD1C (2274 to 2498 residues) (unknown origin) expressed in Escherichia coli assessed as dissociation constant incubated for 60 secs by SPR analysis	kd	8.0600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases reaction, decreases methylation, affects binding, affects folding	2
trichostatin A	decreases expression, increases expression	2
bisphenol S	decreases methylation, affects binding, increases reaction	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
geraniol	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3795796	Binding	Inhibition of KDM3C (unknown origin) using substrate peptide/ascorbate/2-OG/ Fe(2) as substrate preincubated for 15 mins followed by addition of substrate peptide/ ascorbate/2-OG/ Fe(2) measured after 1 hr by AlphaLISA method	Discovery of KDM5A inhibitors: Homology modeling, virtual screening and structure-activity relationship analysis. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ST76	HAP1 JMJD1C (-) 1	Cancer cell line	Male
CVCL_ST77	HAP1 JMJD1C (-) 2	Cancer cell line	Male
CVCL_ST78	HAP1 JMJD1C (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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,
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
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
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study