ATXN7L3

Summary

ATXN7L3 (ataxin 7 like 3, HGNC:25416) is a protein-coding gene on chromosome 17q21.31, encoding Ataxin-7-like protein 3 (Q14CW9). Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. It is a selective cancer dependency (DepMap: 30.1% of cell lines).

Enables transcription coactivator activity. Involved in positive regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Located in nucleus. Part of DUBm complex and SAGA complex.

Source: NCBI Gene 56970 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 57 total — 1 pathogenic
• Phenotypes (HPO): 85
• Cancer dependency (DepMap): dependent in 30.1% of screened cell lines
• MANE Select transcript: NM_001382309

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25416
Approved symbol	ATXN7L3
Name	ataxin 7 like 3
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761G2113
Ensembl gene	ENSG00000087152
Ensembl biotype	protein_coding
OMIM	619010
Entrez	56970

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000389384, ENST00000454077, ENST00000586688, ENST00000587022, ENST00000587097, ENST00000589607, ENST00000589805, ENST00000590169, ENST00000590537, ENST00000591295, ENST00000591807, ENST00000593073, ENST00000889834, ENST00000889835, ENST00000889836, ENST00000889837, ENST00000889838, ENST00000889839, ENST00000913339, ENST00000913340, ENST00000913341, ENST00000913342, ENST00000913343, ENST00000913344, ENST00000962113, ENST00000962114, ENST00000962115

RefSeq mRNA: 9 — MANE Select: NM_001382309 NM_001382308, NM_001382309, NM_001382310, NM_001382311, NM_001382312, NM_001382313, NM_001382314, NM_001382315, NM_001382316

CCDS: CCDS42345, CCDS45697

Canonical transcript exons

ENST00000587097 — 13 exons

Exon	Start	End
ENSE00001059563	44196396	44196418
ENSE00001297504	44196034	44196079
ENSE00001320893	44198020	44198130
ENSE00001505697	44191805	44194411
ENSE00001505699	44196929	44197026
ENSE00001505701	44197228	44197399
ENSE00001505703	44197598	44197730
ENSE00002803383	44199496	44199884
ENSE00003480073	44195097	44195140
ENSE00003516271	44195419	44195487
ENSE00003528220	44194768	44194839
ENSE00003540451	44195800	44195828
ENSE00003611222	44194517	44194674

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3228 / max 237.9970, expressed in 1810 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166321	9.8404	1788
166322	2.7679	1419
166315	2.5150	1441
166323	2.3626	1342
166324	0.2812	135
166319	0.2331	91
166318	0.1935	72
166320	0.1292	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	97.72	gold quality
cortical plate	UBERON:0005343	96.92	gold quality
right frontal lobe	UBERON:0002810	96.77	gold quality
anterior cingulate cortex	UBERON:0009835	96.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.51	gold quality
frontal cortex	UBERON:0001870	96.32	gold quality
neocortex	UBERON:0001950	95.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.92	gold quality
granulocyte	CL:0000094	95.44	gold quality
monocyte	CL:0000576	95.41	gold quality
leukocyte	CL:0000738	95.30	gold quality
amygdala	UBERON:0001876	95.27	gold quality
kidney epithelium	UBERON:0004819	94.94	silver quality
cerebral cortex	UBERON:0000956	94.77	gold quality
hypothalamus	UBERON:0001898	93.99	gold quality
stromal cell of endometrium	CL:0002255	93.89	gold quality
forebrain	UBERON:0001890	93.71	gold quality
left ventricle myocardium	UBERON:0006566	93.67	silver quality
cardiac muscle of right atrium	UBERON:0003379	93.56	silver quality
ganglionic eminence	UBERON:0004023	93.56	gold quality
lower esophagus mucosa	UBERON:0035834	93.55	gold quality
brain	UBERON:0000955	93.39	gold quality
superior frontal gyrus	UBERON:0002661	93.34	gold quality
upper arm skin	UBERON:0004263	93.26	silver quality
temporal lobe	UBERON:0001871	93.23	gold quality
vermiform appendix	UBERON:0001154	93.22	gold quality
metanephros cortex	UBERON:0010533	93.12	gold quality
sural nerve	UBERON:0015488	93.02	gold quality
cerebellar cortex	UBERON:0002129	92.99	gold quality
cerebellar hemisphere	UBERON:0002245	92.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting ATXN7L3, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6793-5P	99.97	65.95	758
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-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 30.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• ATXN7L3, USP22, & ENY2 are required cofactors for full transcriptional activity by nuclear receptors. The deubiquitinase activity of TFTC/STAGA HAT counteracts heterochromatin silencing & is a positive cofactor for in vivo nuclear receptor activation. (PMID:18206972)
• The solution structures of the SCA7 domain of both ATXN7 and ATXN7L3 reveal a new, common zinc-finger motif at the heart of two distinct folds, providing a molecular basis for the observed functional differences. (PMID:20634802)
• Downregulation of ATXN7L3 by short hairpin RNA speci fi cally inactivated the SAGA deubiquitination activity, leading to a strong increase of global H2B ubiquitination and a moderate increase of H2A ubiquitination. (PMID:21746879)
• ATXN7L3 and ENY2 orchestrate activities of multiple deubiquitinating enzymes, including USP27x and USP51, and that imbalances in these activities likely potentiate human diseases including cancer. (PMID:27132940)
• Long non-coding RNA DSCAM-AS1 contributes to the tumorigenesis of cervical cancer by targeting miR-877-5p/ATXN7L3 axis. (PMID:31737900)
• ATXN7L3 positively regulates SMAD7 transcription in hepatocellular carcinoma with growth inhibitory function. (PMID:33186807)
• Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia. (PMID:35192684)
• Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL. (PMID:35316324)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	atxn7l3a	ENSDARG00000029331
mus_musculus	Atxn7l3	ENSMUSG00000059995
rattus_norvegicus	Atxn7l3	ENSRNOG00000020930

Paralogs (4): ATXN7L1 (ENSG00000146776), ATXN7L2 (ENSG00000162650), ATXN7 (ENSG00000163635), ATXN7L3B (ENSG00000253719)

Protein

Protein identifiers

Ataxin-7-like protein 3 — Q14CW9 (reviewed: Q14CW9)

Alternative names: SAGA-associated factor 11 homolog

All UniProt accessions (6): Q14CW9, K7EJK2, K7EKG9, K7EMZ3, K7ENU1, K7ENZ2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. Within the complex, it is required to recruit USP22 and ENY2 into the SAGA complex. Regulates H2B monoubiquitination (H2Bub1) levels. Affects subcellular distribution of ENY2, USP22 and ATXN7L3B.

Subunit / interactions. Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H, TAF10, TRRAP and USP22. Within the SAGA complex, ENY2, ATXN7, ATXN7L3, and USP22 form an additional subcomplex of SAGA called the DUB module (deubiquitination module). Interacts directly with ENY2 and USP22.

Subcellular location. Nucleus.

Domain organisation. The long N-terminal helix forms part of the ‘assembly lobe’ of the SAGA deubiquitination module. The C-terminal SGF11-type zinc-finger domain together with the C-terminal catalytic domain of USP22 forms the ‘catalytic lobe’ of the SAGA deubiquitination module.

Similarity. Belongs to the SGF11 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14CW9-1	1	yes
Q14CW9-2	2

RefSeq proteins (9): NP_001369237, NP_001369238, NP_001369239, NP_001369240, NP_001369241, NP_001369242, NP_001369243, NP_001369244, NP_001369245 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013243	SCA7_dom	Domain
IPR013246	SAGA_su_Sgf11	Family
IPR051078	SGF11	Family

Pfam: PF08209, PF08313

UniProt features (19 total): modified residue 5, compositionally biased region 3, helix 2, turn 2, region of interest 2, chain 1, domain 1, splice variant 1, strand 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KKT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14CW9-F1	65.82	0.14

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 (5): 278, 281, 326, 129, 131

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 163 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_RNA_SPLICING, GOBP_DNA_DAMAGE_RESPONSE, GOCC_RNA_POLYMERASE_COMPLEX, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GCM_NF2, GOBP_REGULATION_OF_RNA_SPLICING, GOCC_SAGA_COMPLEX, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (5): regulation of DNA repair (GO:0006282), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), regulation of RNA splicing (GO:0043484), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): SAGA complex (GO:0000124), nucleus (GO:0005634), transcription factor TFTC complex (GO:0033276), DUBm complex (GO:0071819), SAGA-type complex (GO:0070461)

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
regulation of DNA-templated transcription	2
SAGA-type complex	2
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
cellular component organization	1
transcription by RNA polymerase II	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
transition metal ion binding	1
binding	1
cation binding	1
DUBm complex	1
peptidase complex	1
intracellular membrane-bounded organelle	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
nuclear protein-containing complex	1
histone acetyltransferase complex	1

Protein interactions and networks

STRING

1285 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN7L3	ENY2	Q9NPA8	995
ATXN7L3	ATXN7	O15265	994
ATXN7L3	USP22	Q9UPT9	991
ATXN7L3	ATXN7L2	Q5T6C5	861
ATXN7L3	ATXN7L1	Q9ULK2	853
ATXN7L3	USP51	Q70EK9	844
ATXN7L3	USP27X	A6NNY8	836
ATXN7L3	TRRAP	Q9Y4A5	680
ATXN7L3	SUPT20H	Q8NEM7	668
ATXN7L3	TAF6L	Q9Y6J9	665
ATXN7L3	TADA3	O75528	643
ATXN7L3	SGF29	Q96ES7	595
ATXN7L3	ZUP1	Q96AP4	585
ATXN7L3	KAT2A	Q92830	563
ATXN7L3	KAT2B	Q92831	540

IntAct

37 interactions, top by confidence:

A	B	Type	Score
ATXN7L3	ENY2	psi-mi:“MI:0915”(physical association)	0.840
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP22	psi-mi:“MI:0915”(physical association)	0.560
SUPT20H	ATXN7	psi-mi:“MI:0914”(association)	0.530
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
USP22	CNOT1	psi-mi:“MI:0914”(association)	0.350
ATXN7	SUPT3H	psi-mi:“MI:0914”(association)	0.350
SGF29	USP27X	psi-mi:“MI:0914”(association)	0.350
ENY2	EIF3CL	psi-mi:“MI:0914”(association)	0.350
USP22	ARPC2	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	USP27X	psi-mi:“MI:0914”(association)	0.350
USP51	GSTA1	psi-mi:“MI:0914”(association)	0.350
USP51	USP27X	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	GABARAP	psi-mi:“MI:0914”(association)	0.350
KLF6	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
MYC	SETD1A	psi-mi:“MI:2364”(proximity)	0.270
ENY2	ATXN7L3	psi-mi:“MI:0915”(physical association)	0.000
USP22	ATXN7L3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (262): ATXN7L3 (Affinity Capture-MS), TRRAP (Affinity Capture-MS), CCDC101 (Affinity Capture-MS), USP22 (Affinity Capture-MS), USP27X (Affinity Capture-MS), TAF9B (Affinity Capture-MS), TAF9 (Affinity Capture-MS), ATXN7L2 (Affinity Capture-MS), ATXN7 (Affinity Capture-MS), TADA1 (Affinity Capture-MS), ATXN7L1 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), TAF12 (Affinity Capture-MS), ENY2 (Affinity Capture-MS), KAT2B (Affinity Capture-MS)

ESM2 similar proteins: A1L209, A2AWT3, B0W8L4, B1PM81, B3M881, B3NHQ1, B4GZZ4, B4IFU5, B4J1U4, B4J1U5, B4KY72, B4LDA6, B4MVH6, B4PJ01, B4QPV0, F4IDY7, O94818, O94880, P61406, P97496, Q08AX9, Q14CW9, Q17CJ5, Q2LYX9, Q3UG20, Q498T3, Q5RBA1, Q5RIX9, Q5TYQ8, Q5ZK36, Q5ZKG2, Q66KD5, Q69ZW3, Q6DD45, Q6DFC8, Q6P2L6, Q7PXG4, Q7ZUF2, Q7ZX31, Q8IZD2

Diamond homologs: A1L209, A2AWT3, A5DZI5, A7TSM3, B0W8L4, B1PM81, B3M881, B3NHQ1, B4GZZ4, B4IFU5, B4J1U4, B4J1U5, B4KY72, B4LDA6, B4MVH6, B4N4E1, B4PJ01, B4QPV0, Q14CW9, Q17CJ5, Q2LYX9, Q3UD01, Q5FC18, Q751G1, Q7PXG4, Q94BV2, Q96GX2, Q9VVR6, A3LPV8, Q5A4H4, Q6BWF6, Q6CR57, Q6FKC2, A6ZWK1, B3LL20, Q03067

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATXN7L3	“form complex”	“SAGA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
HATs acetylate histones	8	28.8×	2e-08
Chromatin organization	6	22.2×	2e-05
Chromatin modifying enzymes	6	19.7×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA repair	9	88.8×	9e-14
regulation of RNA splicing	8	62.5×	5e-11
protein deubiquitination	5	31.7×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	40
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4644711	Single allele	Pathogenic

SpliceAI

1608 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44194407:GGTAC:G	acceptor_gain	1.0000
17:44194408:GTAC:G	acceptor_gain	1.0000
17:44194409:TAC:T	acceptor_gain	1.0000
17:44194410:AC:A	acceptor_gain	1.0000
17:44194411:CCTG:C	acceptor_gain	1.0000
17:44194412:C:CA	acceptor_loss	1.0000
17:44194412:C:CC	acceptor_gain	1.0000
17:44194414:G:GC	acceptor_gain	1.0000
17:44194513:GTAC:G	donor_loss	1.0000
17:44194514:TACCT:T	donor_loss	1.0000
17:44194515:A:C	donor_loss	1.0000
17:44194516:C:CG	donor_loss	1.0000
17:44194518:TAG:T	donor_gain	1.0000
17:44194519:AGA:A	donor_gain	1.0000
17:44194528:C:A	donor_gain	1.0000
17:44194670:GGACA:G	acceptor_gain	1.0000
17:44194671:GACA:G	acceptor_gain	1.0000
17:44194672:ACA:A	acceptor_gain	1.0000
17:44194673:CA:C	acceptor_gain	1.0000
17:44194673:CAC:C	acceptor_gain	1.0000
17:44194675:C:CC	acceptor_gain	1.0000
17:44194766:A:AC	donor_gain	1.0000
17:44194766:ACG:A	donor_gain	1.0000
17:44194767:C:CC	donor_gain	1.0000
17:44194767:CG:C	donor_gain	1.0000
17:44194767:CGC:C	donor_gain	1.0000
17:44195412:C:CA	donor_gain	1.0000
17:44195483:TTATA:T	acceptor_gain	1.0000
17:44195484:TATA:T	acceptor_gain	1.0000
17:44195485:ATA:A	acceptor_gain	1.0000

AlphaMissense

2058 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44194803:C:A	R234S	1.000
17:44194803:C:G	R234S	1.000
17:44194804:C:A	R234M	1.000
17:44194804:C:G	R234T	1.000
17:44194805:T:A	R234W	1.000
17:44194805:T:C	R234G	1.000
17:44194818:G:C	H229Q	1.000
17:44194818:G:T	H229Q	1.000
17:44194819:T:C	H229R	1.000
17:44194820:G:C	H229D	1.000
17:44194820:G:T	H229N	1.000
17:44194827:G:C	C226W	1.000
17:44194828:C:A	C226F	1.000
17:44194828:C:G	C226S	1.000
17:44194828:C:T	C226Y	1.000
17:44194829:A:C	C226G	1.000
17:44194829:A:G	C226R	1.000
17:44194829:A:T	C226S	1.000
17:44195097:C:A	R222M	1.000
17:44195097:C:G	R222T	1.000
17:44195102:G:C	C220W	1.000
17:44195103:C:A	C220F	1.000
17:44195103:C:G	C220S	1.000
17:44195103:C:T	C220Y	1.000
17:44195104:A:G	C220R	1.000
17:44195104:A:T	C220S	1.000
17:44195106:A:G	M219T	1.000
17:44195115:G:A	T216I	1.000
17:44195119:G:C	H215D	1.000
17:44195124:G:A	S213F	1.000

dbSNP variants (sampled 300 via entrez): RS1000282150 (17:44201150 T>G), RS1000472549 (17:44199889 G>C), RS1000503756 (17:44200089 C>A,G,T), RS1000673194 (17:44195313 G>A,T), RS1001342076 (17:44198200 C>G,T), RS1001394212 (17:44198512 A>G), RS1001396665 (17:44197481 T>C), RS1001452512 (17:44192602 A>G), RS1001481539 (17:44192351 G>C), RS1002143097 (17:44200524 G>A,C), RS1002176106 (17:44200674 G>A), RS1002344429 (17:44196649 G>A), RS1002398696 (17:44196898 G>A), RS1002453280 (17:44191822 G>A), RS1003032459 (17:44198572 G>A)

Disease associations

OMIM: gene MIM:619010 | disease phenotypes: MIM:621377

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant
Mendelian neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (3): Harel-Tora neurodevelopmental syndrome (MONDO:0980703), complex neurodevelopmental disorder (MONDO:0100038), Mendelian neurodevelopmental disorder (MONDO:0100500)

Orphanet (0):

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000160	Narrow mouth
HP:0000189	Narrow palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000300	Oval face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000421	Epistaxis
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000540	Hypermetropia
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000646	Amblyopia
HP:0000678	Dental crowding

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_24	Bipolar disorder	2.000000e-08
GCST008839_3	Height	6.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Ozone	increases abundance, affects expression, affects cotreatment, decreases expression	3
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression, decreases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
CGP 52608	increases reaction, affects binding	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Leflunomide	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation, decreases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	increases methylation	1
Volatile Organic Compounds	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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