CHAMP1

Summary

CHAMP1 (chromosome alignment maintaining phosphoprotein 1, HGNC:20311) is a protein-coding gene on chromosome 13q34, encoding Chromosome alignment-maintaining phosphoprotein 1 (Q96JM3). Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis.

This gene encodes a zinc finger protein that functions as a regulator of chromosome segregation in mitosis. The encoded protein is required for correct alignment of chromosomes on the metaphase plate, and plays a role in maintaining the attachment of sister kinetochores to microtubules from opposite spindle poles. Mutations in this gene are associated with an autosomal dominant form of intellectual disability.

Source: NCBI Gene 283489 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 340 total — 39 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_032436

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20311
Approved symbol	CHAMP1
Name	chromosome alignment maintaining phosphoprotein 1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	CAMP, CHAMP
Ensembl gene	ENSG00000198824
Ensembl biotype	protein_coding
OMIM	616327
Entrez	283489

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000361283, ENST00000463003, ENST00000478022, ENST00000643483, ENST00000644294, ENST00000645174, ENST00000646155, ENST00000646956, ENST00000700527, ENST00000700528, ENST00000931582

RefSeq mRNA: 3 — MANE Select: NM_032436 NM_001164144, NM_001164145, NM_032436

CCDS: CCDS9545

Canonical transcript exons

ENST00000361283 — 3 exons

Exon	Start	End
ENSE00001366333	114321110	114321232
ENSE00003829028	114314503	114314643
ENSE00003830327	114323788	114327322

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 93.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.2870 / max 301.7887, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136297	26.8660	1811
136296	1.0687	570
136299	0.3522	162

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	93.57	gold quality
cortical plate	UBERON:0005343	89.73	gold quality
secondary oocyte	CL:0000655	88.80	gold quality
ganglionic eminence	UBERON:0004023	88.10	gold quality
colonic epithelium	UBERON:0000397	87.21	gold quality
tibialis anterior	UBERON:0001385	86.21	silver quality
cardiac muscle of right atrium	UBERON:0003379	85.84	silver quality
thymus	UBERON:0002370	84.86	gold quality
upper leg skin	UBERON:0004262	84.84	gold quality
left ventricle myocardium	UBERON:0006566	84.80	silver quality
stromal cell of endometrium	CL:0002255	84.39	gold quality
ventricular zone	UBERON:0003053	84.22	gold quality
upper arm skin	UBERON:0004263	83.59	gold quality
bone marrow cell	CL:0002092	83.45	gold quality
placenta	UBERON:0001987	83.32	gold quality
smooth muscle tissue	UBERON:0001135	83.31	gold quality
lymph node	UBERON:0000029	83.07	gold quality
kidney epithelium	UBERON:0004819	82.87	gold quality
pigmented layer of retina	UBERON:0001782	82.82	gold quality
jejunal mucosa	UBERON:0000399	82.43	gold quality
rectum	UBERON:0001052	82.25	gold quality
trabecular bone tissue	UBERON:0002483	82.02	gold quality
gastrocnemius	UBERON:0001388	81.94	gold quality
cerebellar vermis	UBERON:0004720	81.85	gold quality
leukocyte	CL:0000738	81.72	gold quality
duodenum	UBERON:0002114	81.71	gold quality
descending thoracic aorta	UBERON:0002345	81.70	gold quality
muscle of leg	UBERON:0001383	81.65	gold quality
vermiform appendix	UBERON:0001154	81.61	gold quality
bone marrow	UBERON:0002371	81.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	174.25
E-ANND-3	no	3.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting CHAMP1, 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-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-105-5P	99.54	69.24	2060

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• The study reports a novel protein involved in kinetochore-microtubule attachment, chromosome alignment-maintaining phosphoprotein (CAMP) (C13orf8, ZNF828). (PMID:21063390)
• De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment. (PMID:26340335)
• These data suggest a pathogenic mechanism of the CHAMP1-associated intellectual disability syndrome mediated by direct interacting partners of CHAMP1, several of which are involved in chromo/kinetochore-related disorders. (PMID:26751395)
• structure-based interaction analyses revealed an unprecedented mechanism involving CAMP’s WK motif. Surprisingly, in one of the crystal forms, the MAD2L2-CAMP complex formed a dimeric structure in which the C-terminal region of MAD2L2 was swapped and adopted an immature structure (PMID:28887307)
• Neurodevelopmental phenotypes in individuals with pathogenic variants in CHAMP1. (PMID:34021018)
• Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression. (PMID:34107118)
• CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair. (PMID:36044844)
• Chromodomain on Y-like 2 (CDYL2) implicated in mitosis and genome stability regulation via interaction with CHAMP1 and POGZ. (PMID:36658409)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Champ1	ENSMUSG00000047710
rattus_norvegicus	Champ1	ENSRNOG00000000112

Protein

Protein identifiers

Chromosome alignment-maintaining phosphoprotein 1 — Q96JM3 (reviewed: Q96JM3)

Alternative names: Zinc finger protein 828

All UniProt accessions (4): Q96JM3, A0A2R8Y4S6, A0A2R8Y735, S4R3K0

UniProt curated annotations — full annotation on UniProt →

Function. Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore.

Subunit / interactions. Interacts with MAD2L2. Interacts with POGZ, CBX1, CBX3 and CBX5.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore. Cytoplasm. Cytoskeleton. Spindle.

Post-translational modifications. Phosphorylated by CDK1. Mitotic phosphorylation is required for the attachment of spindle microtubules to the kinetochore.

RefSeq proteins (3): NP_001157616, NP_001157617, NP_115812* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR039330	CAMP	Family

UniProt features (79 total): modified residue 52, compositionally biased region 7, cross-link 6, region of interest 5, sequence variant 3, sequence conflict 3, chain 1, zinc finger region 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6EKJ	X-RAY DIFFRACTION	1.6
6EKL	X-RAY DIFFRACTION	1.6
5XPT	X-RAY DIFFRACTION	2.1
5XPU	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JM3-F1	48.04	0.01

Functional residue map

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

Post-translational modifications (58): 1, 87, 108, 173, 184, 204, 214, 217, 244, 247, 253, 264, 275, 282, 286, 297, 308, 319, 344, 355 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 473 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_INSULIN_SECRETION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS

GO Biological Process (4): sister chromatid biorientation (GO:0031134), protein localization to kinetochore (GO:0034501), protein localization to microtubule (GO:0035372), attachment of mitotic spindle microtubules to kinetochore (GO:0051315)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): kinetochore (GO:0000776), condensed chromosome (GO:0000793), nucleus (GO:0005634), nucleoplasm (GO:0005654), spindle (GO:0005819), nuclear body (GO:0016604), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	5
attachment of spindle microtubules to kinetochore	2
cellular anatomical structure	2
sister chromatid segregation	1
protein localization to chromosome, centromeric region	1
protein localization to condensed chromosome	1
protein localization to microtubule cytoskeleton	1
mitotic metaphase chromosome alignment	1
mitotic cell cycle process	1
transition metal ion binding	1
binding	1
cation binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
microtubule cytoskeleton	1
nucleoplasm	1
chromosomal region	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHAMP1	MAD2L2	Q9UI95	662
CHAMP1	POGZ	Q7Z3K3	576
CHAMP1	CENPE	Q02224	503
CHAMP1	CENPF	P49454	465
CHAMP1	SAYSD1	Q9NPB0	460
CHAMP1	HUWE1	Q7Z6Z7	443
CHAMP1	CEP57	Q86XR8	442
CHAMP1	KNL1	Q8NG31	441
CHAMP1	NDE1	Q9NXR1	415
CHAMP1	PSD4	Q8NDX1	412
CHAMP1	REV3L	O60673	396
CHAMP1	TRMT13	Q9NUP7	384
CHAMP1	TPGS2	Q68CL5	380
CHAMP1	ERLIN1	O75477	374
CHAMP1	SHLD2	Q86V20	366

IntAct

115 interactions, top by confidence:

A	B	Type	Score
CHAMP1	MAD2L2	psi-mi:“MI:0915”(physical association)	0.820
CHAMP1	MAD2L2	psi-mi:“MI:0407”(direct interaction)	0.820
PHF19	EED	psi-mi:“MI:0914”(association)	0.730
ZNF576	ZBED1	psi-mi:“MI:0914”(association)	0.640
USP20	HIF1A	psi-mi:“MI:0914”(association)	0.630
MAD2L2	CBX5	psi-mi:“MI:0914”(association)	0.530
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
CBX5	WIZ	psi-mi:“MI:0914”(association)	0.530
CBX1	KPNA3	psi-mi:“MI:0914”(association)	0.530
ZNF408	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF428	PIP4K2A	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
ZNF428	S100A10	psi-mi:“MI:0914”(association)	0.530
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
HOMEZ	CPEB4	psi-mi:“MI:0914”(association)	0.530
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
Mad2l2	CALU	psi-mi:“MI:0915”(physical association)	0.400
Kat8	HCFC1	psi-mi:“MI:0914”(association)	0.350
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Mad2l2	CHD1	psi-mi:“MI:0914”(association)	0.350
Cbx1		psi-mi:“MI:0914”(association)	0.350
Tp53bp1	WBP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (202): CHAMP1 (Protein-peptide), CHAMP1 (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), POGZ (Affinity Capture-MS), CBX3 (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), CHAMP1 (Reconstituted Complex), CHAMP1 (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), CHAMP1 (Co-fractionation), CHAMP1 (Co-fractionation), CHAMP1 (Co-fractionation), ZMYM4 (Affinity Capture-MS), EEF1E1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YWL9, A0A0J9YY54, A5D7L8, A6NJ88, D3YZV8, E9Q6E9, F1LWT0, O14686, O15069, P18583, P51843, P62521, P79386, Q0P6D6, Q13342, Q2EG98, Q3V3Q4, Q4R729, Q5HY64, Q5JRC9, Q5QGU6, Q6ITT4, Q6PDK2, Q70KF4, Q8CHD8, Q8N1P7, Q8N660, Q8N693, Q8N7U7, Q8NA70, Q8NDZ2, Q8TCU4, Q96JM3, Q99KW3, Q9BE18, Q9BG93, Q9BG94, Q9BG96, Q9BG97, Q9BXX2

Diamond homologs: Q8K327, Q96JM3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CHAMP1	up-regulates	Chromosome_segregation
CHAMP1	“up-regulates activity”	MAD2L2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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
Transcriptional Regulation by E2F6	5	14.6×	3e-03
Dengue Virus-Host Interactions	12	5.5×	4e-04
mRNA Splicing - Major Pathway	10	5.5×	2e-03
SARS-CoV Infections	9	5.0×	7e-03
Viral Infection Pathways	16	4.9×	8e-05
Infectious disease	17	4.2×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	7	13.2×	9e-04
negative regulation of translation	7	10.2×	2e-03
chromatin remodeling	11	5.9×	1e-03
DNA damage response	11	4.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	19
Uncertain significance	171
Likely benign	80
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064505	NM_032436.4(CHAMP1):c.959dup (p.Pro320_Arg321insTer)	Pathogenic
1065455	NM_032436.4(CHAMP1):c.647_649dup (p.Ser217Ter)	Pathogenic
1164024	NM_032436.4(CHAMP1):c.1995dup (p.Ser666Ter)	Pathogenic
1322073	NM_032436.4(CHAMP1):c.1692dup (p.Lys565fs)	Pathogenic
1338820	NM_032436.4(CHAMP1):c.1741del (p.Glu581fs)	Pathogenic
1686872	NM_032436.4(CHAMP1):c.1043G>A (p.Trp348Ter)	Pathogenic
1686873	NM_032436.4(CHAMP1):c.1876_1877del (p.Ser626fs)	Pathogenic
208414	NM_032436.4(CHAMP1):c.635del (p.Pro212fs)	Pathogenic
208415	NM_032436.4(CHAMP1):c.1192C>T (p.Arg398Ter)	Pathogenic
208416	NM_032436.4(CHAMP1):c.1768C>T (p.Gln590Ter)	Pathogenic
208417	NM_032436.4(CHAMP1):c.1866_1867del (p.Asp622fs)	Pathogenic
210049	NM_032436.4(CHAMP1):c.1002G>A (p.Trp334Ter)	Pathogenic
210050	NM_032436.4(CHAMP1):c.1489C>T (p.Arg497Ter)	Pathogenic
217907	NM_032436.4(CHAMP1):c.1544G>A (p.Trp515Ter)	Pathogenic
217908	NM_032436.4(CHAMP1):c.1044del (p.Pro347_Trp348insTer)	Pathogenic
217909	NM_032436.4(CHAMP1):c.542_543del (p.Ser181fs)	Pathogenic
217910	NM_032436.4(CHAMP1):c.1945C>T (p.Gln649Ter)	Pathogenic
217916	NM_032436.4(CHAMP1):c.1969C>T (p.Gln657Ter)	Pathogenic
2430307	NM_032436.4(CHAMP1):c.1918_1919del (p.Asp640fs)	Pathogenic
2442350	NM_032436.4(CHAMP1):c.2068_2069del (p.Glu690fs)	Pathogenic
2575934	NM_032436.4(CHAMP1):c.1800_1801insG (p.Leu601fs)	Pathogenic
280855	NM_032436.4(CHAMP1):c.1850dup (p.Lys618fs)	Pathogenic
3233724	NM_032436.4(CHAMP1):c.2000_2001del (p.Lys667fs)	Pathogenic
3244202	NC_000013.10:g.(?115078383)(115109878_?)del	Pathogenic
3343943	NM_032436.4(CHAMP1):c.2067_2070del (p.Glu690fs)	Pathogenic
3491873	NM_032436.4(CHAMP1):c.1170del (p.Ser389_Trp390insTer)	Pathogenic
430233	NM_032436.4(CHAMP1):c.403C>T (p.Gln135Ter)	Pathogenic
4819158	NM_032436.4(CHAMP1):c.292C>T (p.Gln98Ter)	Pathogenic
503867	NM_032436.4(CHAMP1):c.730delinsGC (p.Ser244fs)	Pathogenic
521832	NM_032436.4(CHAMP1):c.1952C>G (p.Ser651Ter)	Pathogenic

SpliceAI

558 predictions. Top by Δscore:

Variant	Effect	Δscore
13:114314639:GACCG:G	donor_gain	1.0000
13:114314640:ACCGG:A	donor_loss	1.0000
13:114314641:CCGG:C	donor_loss	1.0000
13:114314642:CGGTG:C	donor_loss	1.0000
13:114314644:G:GC	donor_loss	1.0000
13:114314644:G:GG	donor_gain	1.0000
13:114314645:T:A	donor_loss	1.0000
13:114321216:GTCT:G	donor_gain	0.9900
13:114323787:GCA:G	acceptor_gain	0.9900
13:114314650:A:T	donor_gain	0.9800
13:114315749:G:GT	donor_gain	0.9800
13:114315765:AT:A	donor_gain	0.9800
13:114314795:G:T	donor_gain	0.9700
13:114323787:GCAGT:G	acceptor_gain	0.9700
13:114321229:GCAG:G	donor_gain	0.9600
13:114321228:AGCAG:A	donor_loss	0.9400
13:114321230:CAGGT:C	donor_loss	0.9400
13:114321231:AG:A	donor_loss	0.9400
13:114321232:GGTA:G	donor_loss	0.9400
13:114321233:G:A	donor_loss	0.9400
13:114321234:T:TC	donor_loss	0.9400
13:114321215:TGTC:T	donor_gain	0.9300
13:114314646:GAGGA:G	donor_loss	0.9200
13:114321235:AA:A	donor_loss	0.9200
13:114314641:CCG:C	donor_gain	0.9100
13:114314747:TCC:T	donor_gain	0.9100
13:114323786:A:AG	acceptor_gain	0.9100
13:114323787:G:GG	acceptor_gain	0.9100
13:114314671:G:T	donor_gain	0.9000
13:114314649:G:GT	donor_gain	0.8900

AlphaMissense

5259 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:114324032:T:C	C64R	1.000
13:114325952:C:A	R704S	1.000
13:114325964:A:G	K708E	1.000
13:114325967:T:C	Y709H	1.000
13:114325967:T:G	Y709D	1.000
13:114325968:A:G	Y709C	1.000
13:114325973:T:A	C711S	1.000
13:114325973:T:C	C711R	1.000
13:114325974:G:A	C711Y	1.000
13:114325974:G:C	C711S	1.000
13:114325974:G:T	C711F	1.000
13:114325975:C:G	C711W	1.000
13:114325982:T:C	C714R	1.000
13:114325983:G:A	C714Y	1.000
13:114325984:T:G	C714W	1.000
13:114325995:C:A	A718D	1.000
13:114326000:A:G	K720E	1.000
13:114326001:A:T	K720I	1.000
13:114326002:A:C	K720N	1.000
13:114326002:A:T	K720N	1.000
13:114326003:A:G	K721E	1.000
13:114326004:A:T	K721I	1.000
13:114326005:A:C	K721N	1.000
13:114326005:A:T	K721N	1.000
13:114326006:G:C	G722R	1.000
13:114326006:G:T	G722C	1.000
13:114326007:G:A	G722D	1.000
13:114326013:T:A	V724D	1.000
13:114326016:T:C	L725S	1.000
13:114326016:T:G	L725W	1.000

dbSNP variants (sampled 300 via entrez): RS1000159709 (13:114312772 A>G), RS1000616479 (13:114312990 A>G), RS1000660857 (13:114323315 T>C,G), RS1001436137 (13:114316608 A>G,T), RS1001692028 (13:114322469 A>G), RS1001793332 (13:114315834 TG>T), RS1002124087 (13:114312664 G>C), RS1002202224 (13:114327403 A>G), RS1002311589 (13:114321220 A>G), RS1002453450 (13:114315554 T>G), RS1002469779 (13:114315804 T>C), RS1002818171 (13:114321459 G>A), RS1003346416 (13:114320319 G>A), RS1003456906 (13:114314579 C>G,T), RS1003488147 (13:114314728 G>C,T)

Disease associations

OMIM: gene MIM:616327 | disease phenotypes: MIM:616579

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 40	Definitive	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (7): intellectual disability, autosomal dominant 40 (MONDO:0014699), neurodevelopmental disorder (MONDO:0700092), monosomy 13q34 (MONDO:0019902), complex neurodevelopmental disorder (MONDO:0100038), intellectual disability (MONDO:0001071), obesity disorder (MONDO:0011122), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (6): CHAMP1-related intellectual disability-facial dysmorphism-behavioral abnormalities syndrome (Orphanet:692193), Monosomy 13q34 syndrome (Orphanet:96168), Non-specific syndromic intellectual disability (Orphanet:528084), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000307	Pointed chin
HP:0000322	Short philtrum
HP:0000369	Low-set ears
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000582	Upslanted palpebral fissure
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001344	Absent speech
HP:0001357	Plagiocephaly
HP:0001382	Joint hypermobility
HP:0001537	Umbilical hernia
HP:0001540	Diastasis recti
HP:0002020	Gastroesophageal reflux
HP:0002066	Gait ataxia
HP:0002188	Delayed CNS myelination

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008839_439	Height	1.000000e-11

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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): CHEMBL5724784 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.14	IC50	7210	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178645: Inhibition of ZNF828 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	7.2100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
ferrous chloride	decreases expression	1
coumarin	affects phosphorylation	1
cupric oxide	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	increases phosphorylation	1
Rotenone	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697375	Binding	Inhibition of ZNF828 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

20 cell lines: 11 transformed cell line, 4 induced pluripotent stem cell, 4 finite cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5MR	GM27978	Induced pluripotent stem cell	Male
CVCL_A9ZJ	GM27912	Transformed cell line	Female
CVCL_B3SD	GM28007	Finite cell line	Male
CVCL_C7LG	GM27963	Finite cell line	Female
CVCL_C7LH	GM27967	Transformed cell line	Female
CVCL_D3AI	GM29104	Induced pluripotent stem cell	Male
CVCL_D6X0	GM28396	Transformed cell line	Male
CVCL_D6X1	GM29325	Induced pluripotent stem cell	Male
CVCL_SI74	HAP1 CHAMP1 (-)	Cancer cell line	Male
CVCL_XC44	GM27408	Finite cell line	Male

Clinical trials (associated diseases)

299 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,
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
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
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
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
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
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
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)
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