ATXN2L

Summary

ATXN2L (ataxin 2 like, HGNC:31326) is a protein-coding gene on chromosome 16p11.2, encoding Ataxin-2-like protein (Q8WWM7). Involved in the regulation of stress granule and P-body formation.

This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene.

Source: NCBI Gene 11273 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 94
• Clinical variants (ClinVar): 191 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_007245

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31326
Approved symbol	ATXN2L
Name	ataxin 2 like
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	A2lp, A2D
Ensembl gene	ENSG00000168488
Ensembl biotype	protein_coding
OMIM	607931
Entrez	11273

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 17 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000325215, ENST00000336783, ENST00000340394, ENST00000382686, ENST00000395547, ENST00000561539, ENST00000561732, ENST00000562583, ENST00000562686, ENST00000562867, ENST00000563314, ENST00000564035, ENST00000564162, ENST00000564284, ENST00000564304, ENST00000564656, ENST00000565845, ENST00000565971, ENST00000566007, ENST00000566080, ENST00000566946, ENST00000567024, ENST00000568266, ENST00000569318, ENST00000570200, ENST00000570284, ENST00000892823, ENST00000933178, ENST00000950635

RefSeq mRNA: 45 — MANE Select: NM_007245 NM_001308230, NM_001387166, NM_001387167, NM_001387168, NM_001387169, NM_001387170, NM_001387171, NM_001387172, NM_001387173, NM_001387174, NM_001387175, NM_001387176, NM_001387177, NM_001387178, NM_001387179, NM_001387180, NM_001387181, NM_001387182, NM_001387183, NM_001387184, NM_001387185, NM_001387186, NM_001387187, NM_001387188, NM_001387189, NM_001387190, NM_001387191, NM_001387192, NM_001387193, NM_001387194, NM_001387195, NM_001387196, NM_001387197, NM_001387198, NM_001387199, NM_001387200, NM_001387202, NM_001387203, NM_001387204, NM_007245, NM_017492, NM_145714, NM_148414, NM_148415, NM_148416

CCDS: CCDS10639, CCDS10640, CCDS10641, CCDS32423, CCDS45451, CCDS58443, CCDS76850

Canonical transcript exons

ENST00000336783 — 22 exons

Exon	Start	End
ENSE00003467996	28835933	28837232
ENSE00003478859	28834343	28834415
ENSE00003486119	28826862	28826986
ENSE00003490796	28830615	28830790
ENSE00003502425	28833439	28833508
ENSE00003518189	28825624	28825680
ENSE00003529511	28826240	28826390
ENSE00003547318	28825366	28825402
ENSE00003559206	28835549	28835758
ENSE00003562167	28829401	28829492
ENSE00003569055	28834506	28834693
ENSE00003571519	28835058	28835187
ENSE00003578152	28834065	28834211
ENSE00003619343	28832817	28832887
ENSE00003632896	28832205	28832399
ENSE00003634958	28825770	28825841
ENSE00003659122	28833059	28833354
ENSE00003674234	28829858	28830058
ENSE00003687395	28830962	28831072
ENSE00003688319	28832496	28832567
ENSE00003690887	28835278	28835399
ENSE00003920494	28822999	28823558

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 164.2313 / max 1601.4756, expressed in 1828 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153388	71.8147	1821
153390	60.2155	1822
153398	12.1875	1678
153392	8.4309	1723
153397	2.8928	1519
153408	1.3574	832
153391	1.2743	795
153396	1.1145	778
153393	0.9441	565
153389	0.8269	433

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.12	gold quality
right testis	UBERON:0004534	99.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.50	gold quality
cerebellar hemisphere	UBERON:0002245	98.22	gold quality
cerebellar cortex	UBERON:0002129	98.17	gold quality
adenohypophysis	UBERON:0002196	98.16	gold quality
lower esophagus mucosa	UBERON:0035834	97.88	gold quality
granulocyte	CL:0000094	97.73	gold quality
type B pancreatic cell	CL:0000169	97.31	gold quality
metanephros cortex	UBERON:0010533	97.24	gold quality
olfactory bulb	UBERON:0002264	97.23	gold quality
body of uterus	UBERON:0009853	97.17	gold quality
left lobe of thyroid gland	UBERON:0001120	97.15	gold quality
right lobe of thyroid gland	UBERON:0001119	97.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.11	gold quality
right uterine tube	UBERON:0001302	96.98	gold quality
body of stomach	UBERON:0001161	96.94	gold quality
endocervix	UBERON:0000458	96.93	gold quality
upper lobe of left lung	UBERON:0008952	96.93	gold quality
right ovary	UBERON:0002118	96.82	gold quality
paraflocculus	UBERON:0005351	96.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.79	gold quality
minor salivary gland	UBERON:0001830	96.74	gold quality
right frontal lobe	UBERON:0002810	96.71	gold quality
ectocervix	UBERON:0012249	96.64	gold quality
skin of abdomen	UBERON:0001416	96.61	gold quality
left ovary	UBERON:0002119	96.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.58	gold quality
cerebellum	UBERON:0002037	96.57	gold quality
pituitary gland	UBERON:0000007	96.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64
E-GEOD-124858	no	30.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting ATXN2L, 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-5692A	100.00	74.40	6850
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 3)

• cellular ataxin-2 concentration is important for the assembly of stress granules and P-bodies, ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 (PMID:17392519)
• ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). (PMID:25748791)
• ATXN2L promotes cell invasiveness and oxaliplatin resistance and can be upregulated by EGF via PI3K/Akt signaling. (PMID:30787271)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atxn2l	ENSDARG00000011597
mus_musculus	Atxn2l	ENSMUSG00000032637
rattus_norvegicus	Atxn2l	ENSRNOG00000018686
drosophila_melanogaster	Atx2	FBGN0041188
caenorhabditis_elegans		WBGENE00000231

Paralogs (1): ATXN2 (ENSG00000204842)

Protein

Protein identifiers

Ataxin-2-like protein — Q8WWM7 (reviewed: Q8WWM7)

Alternative names: Ataxin-2 domain protein, Ataxin-2-related protein

All UniProt accessions (11): Q8WWM7, A0A0C4DGL7, H3BMX1, H3BPQ7, H3BQ14, H3BQX7, H3BRB0, H3BSK9, H3BSQ5, H3BUE3, H3BUF6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of stress granule and P-body formation.

Subunit / interactions. Interacts with MPL/TPOR and EPOR and dissociates after ligand stimulation. Interacts with DDX6, G3BP1, and ATXN2. Interacts with PRMT1. Interacts with CIC and ATXN1.

Subcellular location. Membrane. Cytoplasm. Nucleus speckle. Cytoplasmic granule.

Tissue specificity. Expressed at high levels in thymus, lymph node, spleen, fetal kidney and adult testis. Constitutively associated with MPL and EPOR in hematopoietic cells.

Post-translational modifications. Thrombopoietin triggers the phosphorylation on tyrosine residues in a way that is dependent on MPL C-terminal domain. Asymmetrically dimethylated. Probably methylated by PRMT1.

Miscellaneous. Due to intron retention.

Similarity. Belongs to the ataxin-2 family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q8WWM7-1	1, A2D-A	yes
Q8WWM7-2	2, A2D-B
Q8WWM7-3	3, A2D-C
Q8WWM7-4	4, A2D-D
Q8WWM7-5	5, A2D-E
Q8WWM7-6	6
Q8WWM7-7	7
Q8WWM7-8	8
Q8WWM7-9	9

RefSeq proteins (45): NP_001295159, NP_001374095, NP_001374096, NP_001374097, NP_001374098, NP_001374099, NP_001374100, NP_001374101, NP_001374102, NP_001374103, NP_001374104, NP_001374105, NP_001374106, NP_001374107, NP_001374108, NP_001374109, NP_001374110, NP_001374111, NP_001374112, NP_001374113, NP_001374114, NP_001374115, NP_001374116, NP_001374117, NP_001374118, NP_001374119, NP_001374120, NP_001374121, NP_001374122, NP_001374123, NP_001374124, NP_001374125, NP_001374126, NP_001374127, NP_001374128, NP_001374129, NP_001374131, NP_001374132, NP_001374133, NP_009176, NP_059867, NP_663760, NP_680780, NP_680781, NP_680782 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009604	LsmAD_domain	Domain
IPR009818	PAM2_motif	Conserved_site
IPR025852	SM_dom_ATX	Domain
IPR045117	ATXN2-like	Family
IPR047575	Sm	Domain

Pfam: PF06741, PF07145, PF14438

UniProt features (70 total): modified residue 28, compositionally biased region 14, splice variant 10, region of interest 8, sequence conflict 5, mutagenesis site 2, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWM7-F1	49.52	0.08

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 (29): 1, 103, 111, 118, 207, 238, 264, 306, 309, 335, 339, 349, 361, 391, 409, 449, 493, 496, 557, 558 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
361	no effect on localization to stress granules under stress conditions.
370	no effect on localization to stress granules under stress conditions.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): GCACCTT_MIR18A_MIR18B, MORF_CDK2, MORF_TERF1, MORF_RAF1, GROSS_HYPOXIA_VIA_ELK3_DN, chr16p11, MODULE_206, TGTGTGA_MIR377, ATTACAT_MIR3803P, TCCCCAC_MIR491, GOBP_ORGANELLE_ASSEMBLY, LIAO_METASTASIS, CCAGGGG_MIR331, IIZUKA_LIVER_CANCER_PROGRESSION_G1_G2_DN, GTGTGAG_MIR342

GO Biological Process (2): mRNA metabolic process (GO:0016071), stress granule assembly (GO:0034063)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (6): cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), nuclear speck (GO:0016607), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA metabolic process	1
membraneless organelle assembly	1
nucleic acid binding	1
RNA binding	1
cell adhesion molecule binding	1
binding	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN2L	SH2B1	Q9NRF2	725
ATXN2L	RABEP2	Q9H5N1	654
ATXN2L	ALS2CL	Q60I27	644
ATXN2L	PABPC1	P11940	633
ATXN2L	DCP1A	Q9NPI6	629
ATXN2L	TUFM	P49411	618
ATXN2L	DDX6	P26196	618
ATXN2L	DCP1B	Q8IZD4	608
ATXN2L	ARHGAP17	Q68EM7	607
ATXN2L	FAM98A	Q8NCA5	580
ATXN2L	ATP2A1	O14983	550
ATXN2L	ATP2A3	Q93084	550
ATXN2L	NFATC2IP	Q8NCF5	548
ATXN2L	ATXN1	P54253	538
ATXN2L	ANO2	Q9NQ90	530

IntAct

170 interactions, top by confidence:

A	B	Type	Score
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.820
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
G3BP2	CAPRIN1	psi-mi:“MI:0914”(association)	0.740
ATXN2L	G3BP1	psi-mi:“MI:0915”(physical association)	0.710
G3BP1	ATXN2L	psi-mi:“MI:0914”(association)	0.710
G3BP1	ATXN2L	psi-mi:“MI:0915”(physical association)	0.710
FAM98A	NUFIP2	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
FAM98A	HERC2	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
ATXN2L	ATXN2	psi-mi:“MI:0403”(colocalization)	0.600
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
MCRIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
G3BP2	NUP214	psi-mi:“MI:0914”(association)	0.530
NUFIP2	RELA	psi-mi:“MI:0914”(association)	0.530
NUFIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
ATXN2L	PABPC1	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
FMR1	ACOT7	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430

BioGRID (345): ATXN2L (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), ATXN2L (Co-fractionation), ATXN2L (Co-fractionation), ATXN2L (Co-fractionation), ATXN2L (Co-fractionation), ATXN2L (Co-fractionation), ATXN2L (Co-fractionation), LSM12 (Co-fractionation), PABPC1 (Co-fractionation), PABPC4 (Co-fractionation)

ESM2 similar proteins: A0A0R4IZ84, A0JMU8, A1L1K8, A5D7H5, B2RRE7, O15234, O60293, O75420, P48634, P61129, P61406, Q04637, Q14444, Q1ECZ4, Q1LZB6, Q3TLH4, Q5CZI8, Q5JSZ5, Q5JVS0, Q5M9G3, Q5RAK6, Q5TM26, Q5U236, Q5VK71, Q5XJD3, Q60865, Q6IMN6, Q6MG48, Q6NZJ6, Q7TPM1, Q7TQG1, Q7TQH0, Q7TSC1, Q80XI3, Q86US8, Q8BWW4, Q8BXJ2, Q8BYK8, Q8K3W3, Q8K3X0

Diamond homologs: O70305, Q29A33, Q7TQH0, Q8SWR8, Q8WWM7, Q99700, P53297, Q55DE7, Q94AM9, Q8L793

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATXN2L	down-regulates	MPL	binding
ATXN2L	unknown	DDX6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	41.6×	1e-07
Activation of BAD and translocation to mitochondria	6	40.4×	7e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	35.7×	1e-06
Activation of BH3-only proteins	6	26.4×	6e-06
Intrinsic Pathway for Apoptosis	7	18.1×	6e-06
RHO GTPases activate PKNs	6	16.8×	6e-05
SARS-CoV-1-host interactions	10	15.6×	2e-07
Dengue Virus Genome Translation and Replication	5	14.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	6	24.2×	7e-05
translational initiation	7	16.8×	7e-05
negative regulation of translation	12	15.8×	2e-08
mRNA stabilization	6	14.8×	6e-04
mRNA transport	7	12.4×	4e-04
regulation of alternative mRNA splicing, via spliceosome	6	9.8×	4e-03
RNA splicing	11	6.5×	3e-04
intracellular protein localization	9	6.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	142
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625601	GRCh37/hg19 16p11.2(chr16:28734571-29043450)	Pathogenic

SpliceAI

3481 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28823557:AGGT:A	donor_loss	1.0000
16:28823558:GG:G	donor_loss	1.0000
16:28823559:G:T	donor_loss	1.0000
16:28823560:T:G	donor_loss	1.0000
16:28825403:G:GG	donor_gain	1.0000
16:28825610:A:AG	acceptor_gain	1.0000
16:28825610:AT:A	acceptor_gain	1.0000
16:28825611:T:G	acceptor_gain	1.0000
16:28825611:T:TA	acceptor_gain	1.0000
16:28825615:A:AG	acceptor_gain	1.0000
16:28825615:AACT:A	acceptor_gain	1.0000
16:28825616:A:G	acceptor_gain	1.0000
16:28825618:T:TA	acceptor_gain	1.0000
16:28825621:CAG:C	acceptor_loss	1.0000
16:28825622:A:AG	acceptor_gain	1.0000
16:28825622:AG:A	acceptor_gain	1.0000
16:28825622:AGGT:A	acceptor_gain	1.0000
16:28825623:G:GG	acceptor_gain	1.0000
16:28825623:GG:G	acceptor_gain	1.0000
16:28825623:GGT:G	acceptor_gain	1.0000
16:28825623:GGTG:G	acceptor_gain	1.0000
16:28825678:GTG:G	donor_gain	1.0000
16:28825681:G:C	donor_loss	1.0000
16:28825681:G:GG	donor_gain	1.0000
16:28825682:T:G	donor_loss	1.0000
16:28826238:A:AG	acceptor_gain	1.0000
16:28826238:AGTTT:A	acceptor_gain	1.0000
16:28826239:G:GA	acceptor_gain	1.0000
16:28826239:GT:G	acceptor_gain	1.0000
16:28826239:GTTT:G	acceptor_gain	1.0000

AlphaMissense

6891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:28825633:G:C	G116R	1.000
16:28825633:G:T	G116C	1.000
16:28825639:T:C	Y118H	1.000
16:28825658:T:C	L124P	1.000
16:28825667:T:C	L127P	1.000
16:28825672:G:C	A129P	1.000
16:28825676:T:A	V130D	1.000
16:28825770:G:C	G132R	1.000
16:28825770:G:T	G132C	1.000
16:28825771:G:A	G132D	1.000
16:28825771:G:T	G132V	1.000
16:28825773:T:C	S133P	1.000
16:28825779:T:C	C135R	1.000
16:28825780:G:A	C135Y	1.000
16:28825781:T:G	C135W	1.000
16:28825786:T:A	V137E	1.000
16:28825815:G:A	G147S	1.000
16:28825815:G:C	G147R	1.000
16:28825815:G:T	G147C	1.000
16:28825816:G:A	G147D	1.000
16:28825816:G:T	G147V	1.000
16:28825822:T:C	F149S	1.000
16:28825824:A:G	K150E	1.000
16:28825826:G:C	K150N	1.000
16:28825826:G:T	K150N	1.000
16:28825831:T:C	L152P	1.000
16:28825833:A:C	S153R	1.000
16:28825834:G:T	S153I	1.000
16:28825835:C:A	S153R	1.000
16:28825835:C:G	S153R	1.000

dbSNP variants (sampled 300 via entrez): RS1000477945 (16:28823397 G>A), RS1000656012 (16:28824814 C>T), RS1000671872 (16:28836986 CT>C), RS1000743196 (16:28829577 T>C), RS1001003790 (16:28824686 C>A,T), RS1001370296 (16:28827403 C>G), RS1001472493 (16:28823066 C>T), RS1001588505 (16:28822861 GAT>G), RS1001625427 (16:28830034 G>A,T), RS1002164210 (16:28825225 T>C), RS1002410345 (16:28825488 G>A), RS1002455709 (16:28822868 T>A,G), RS1002483082 (16:28825956 A>T), RS1002560412 (16:28822549 C>A), RS1002589482 (16:28826467 A>G)

Disease associations

OMIM: gene MIM:607931 | disease phenotypes: MIM:613444

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), distal 16p11.2 microdeletion syndrome (MONDO:0013267)

Orphanet (1): Distal 16p11.2 microdeletion syndrome (Orphanet:261222)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

94 associations (top):

Study	Trait	p-value
GCST000830_13	Body mass index	2.000000e-20
GCST002045_2	Educational attainment	1.000000e-07
GCST002598_62	Educational attainment	1.000000e-06
GCST003097_28	Pediatric autoimmune diseases	6.000000e-07
GCST003435_31	Body fat percentage	1.000000e-08
GCST003435_41	Body fat percentage	7.000000e-07
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST004364_11	Intelligence	4.000000e-08
GCST004364_31	Intelligence	1.000000e-08
GCST004557_141	Body mass index	2.000000e-09
GCST004557_211	Body mass index	3.000000e-08
GCST004557_243	Body mass index	2.000000e-15
GCST004557_32	Body mass index	2.000000e-17
GCST004557_69	Body mass index	1.000000e-10
GCST004558_106	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004558_139	Body mass index (joint analysis main effects and physical activity interaction)	8.000000e-10
GCST004558_163	Body mass index (joint analysis main effects and physical activity interaction)	9.000000e-15
GCST004559_107	Body mass index in physically active individuals	2.000000e-13
GCST004559_195	Body mass index in physically active individuals	1.000000e-08
GCST004559_57	Body mass index in physically active individuals	2.000000e-07
GCST005141_25	Cognitive ability (MTAG)	4.000000e-14
GCST005142_40	Cognitive ability	2.000000e-09
GCST005316_202	Intelligence (MTAG)	1.000000e-19
GCST005829_2	Hand grip strength	1.000000e-25
GCST005987_3	Albumin-globulin ratio	6.000000e-10
GCST007044_23	Extremely high intelligence	2.000000e-08
GCST007293_116	Body fat distribution (arm fat ratio)	2.000000e-08
GCST007293_16	Body fat distribution (arm fat ratio)	4.000000e-09
GCST007293_43	Body fat distribution (arm fat ratio)	2.000000e-12

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004784	self reported educational attainment
EFO:0007800	body fat percentage
EFO:0004337	intelligence
EFO:0008002	physical activity measurement
EFO:0006941	grip strength measurement
EFO:0005128	albumin:globulin ratio measurement
EFO:0004341	body fat distribution
EFO:0004338	body weight
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0009902	handedness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067081 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8049439	ATXN2L, IL27, NPIPB8		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.46	Kd	3425	nM	CHEMBL3752910
5.46	ED50	3425	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147930: Binding affinity to human ATXN2L incubated for 45 mins by Kinobead based pull down assay	kd	3.4253	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance, increases activity	3
Air Pollutants	affects expression, increases abundance, increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Ozone	affects expression, increases abundance, affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Particulate Matter	affects expression, increases abundance, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
deoxynivalenol	increases expression	1
sodium arsenate	increases abundance, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650972	Binding	Binding affinity to human ATXN2L incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2SJ	Abcam HEK293T ATXN2L KO	Transformed cell line	Female
CVCL_E1RK	HAP1 ATXN2L (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice