UBAP2L

Summary

UBAP2L (ubiquitin associated protein 2 like, HGNC:29877) is a protein-coding gene on chromosome 1q21.3, encoding Ubiquitin-associated protein 2-like (Q14157). Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage. It is a selective cancer dependency (DepMap: 14.8% of cell lines).

Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida; positive regulation of stress granule assembly; and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex.

Source: NCBI Gene 9898 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (Definitive, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 199 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 85
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 14.8% of screened cell lines
• MANE Select transcript: NM_014847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29877
Approved symbol	UBAP2L
Name	ubiquitin associated protein 2 like
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	NICE-4, KIAA0144
Ensembl gene	ENSG00000143569
Ensembl biotype	protein_coding
OMIM	616472
Entrez	9898

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 46 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000271877, ENST00000343815, ENST00000361546, ENST00000368504, ENST00000412596, ENST00000428595, ENST00000428931, ENST00000433615, ENST00000437652, ENST00000441890, ENST00000456325, ENST00000465855, ENST00000466173, ENST00000475373, ENST00000484696, ENST00000484819, ENST00000489076, ENST00000493867, ENST00000495676, ENST00000613315, ENST00000707139, ENST00000881849, ENST00000881850, ENST00000881851, ENST00000881852, ENST00000881853, ENST00000881854, ENST00000881855, ENST00000881856, ENST00000881857, ENST00000881858, ENST00000881859, ENST00000881860, ENST00000881861, ENST00000881862, ENST00000881863, ENST00000881864, ENST00000881865, ENST00000881866, ENST00000881867, ENST00000881868, ENST00000881869, ENST00000881870, ENST00000881871, ENST00000916747, ENST00000916748, ENST00000916749, ENST00000916750, ENST00000916751, ENST00000916752, ENST00000963338, ENST00000963339, ENST00000963340, ENST00000963341

RefSeq mRNA: 24 — MANE Select: NM_014847 NM_001127320, NM_001287815, NM_001287816, NM_001330730, NM_001375612, NM_001375614, NM_001375615, NM_001375616, NM_001375617, NM_001375618, NM_001375619, NM_001375620, NM_001375621, NM_001375622, NM_001375623, NM_001375624, NM_001375625, NM_001375626, NM_001375627, NM_001375628, NM_001375629, NM_001375630, NM_001375631, NM_014847

CCDS: CCDS1063, CCDS44229, CCDS72925, CCDS81381

Canonical transcript exons

ENST00000428931 — 27 exons

Exon	Start	End
ENSE00001737417	154270200	154270847
ENSE00003461578	154261592	154261697
ENSE00003495012	154266501	154266568
ENSE00003532947	154246204	154246375
ENSE00003544064	154259948	154260029
ENSE00003589915	154255152	154255326
ENSE00003624372	154255683	154255755
ENSE00003644480	154249239	154249437
ENSE00003647611	154260892	154261109
ENSE00003653438	154258977	154259030
ENSE00003658666	154257346	154257434
ENSE00003685880	154257063	154257258
ENSE00003849355	154220955	154220975
ENSE00003889290	154234591	154234759
ENSE00003890134	154228615	154228725
ENSE00003890528	154241513	154241565
ENSE00003890612	154251481	154251653
ENSE00003890811	154243217	154243302
ENSE00003891002	154227282	154227359
ENSE00003892200	154251041	154251318
ENSE00003892496	154253900	154254089
ENSE00003893302	154237024	154237136
ENSE00003893489	154254836	154254890
ENSE00003893573	154236566	154236611
ENSE00003894600	154225084	154225213
ENSE00003894770	154235196	154235291
ENSE00003895998	154268757	154268954

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.2938 / max 642.6341, expressed in 1819 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5470	39.4060	1815
5471	6.2684	1736
5478	1.1985	826
5479	0.8852	588
5472	0.4304	180
5469	0.1052	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.55	gold quality
left ovary	UBERON:0002119	98.09	gold quality
right ovary	UBERON:0002118	98.07	gold quality
skin of abdomen	UBERON:0001416	97.96	gold quality
skin of leg	UBERON:0001511	97.95	gold quality
right lung	UBERON:0002167	97.93	gold quality
endocervix	UBERON:0000458	97.91	gold quality
mucosa of stomach	UBERON:0001199	97.89	gold quality
body of uterus	UBERON:0009853	97.86	gold quality
upper lobe of left lung	UBERON:0008952	97.83	gold quality
stromal cell of endometrium	CL:0002255	97.82	gold quality
ectocervix	UBERON:0012249	97.80	gold quality
nerve	UBERON:0001021	97.77	gold quality
tibial nerve	UBERON:0001323	97.77	gold quality
right lobe of thyroid gland	UBERON:0001119	97.73	gold quality
left lobe of thyroid gland	UBERON:0001120	97.71	gold quality
left uterine tube	UBERON:0001303	97.70	gold quality
right uterine tube	UBERON:0001302	97.65	gold quality
islet of Langerhans	UBERON:0000006	97.59	gold quality
adenohypophysis	UBERON:0002196	97.56	gold quality
left testis	UBERON:0004533	97.55	gold quality
colonic epithelium	UBERON:0000397	97.49	gold quality
right testis	UBERON:0004534	97.46	gold quality
minor salivary gland	UBERON:0001830	97.43	gold quality
upper lobe of lung	UBERON:0008948	97.38	gold quality
thyroid gland	UBERON:0002046	97.30	gold quality
popliteal artery	UBERON:0002250	97.29	gold quality
tibial artery	UBERON:0007610	97.29	gold quality
omental fat pad	UBERON:0010414	97.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting UBAP2L, 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-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-452-3P	99.01	66.25	1241

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• Knockdown of UBAP2L in prostate carcinoma inhibited cell proliferation, migration, and colony formation ability, and blocked cell cycle progression. (PMID:25069639)
• Two different BMI1-containing PcG complexes regulate hematopoietic stem cell activity, which are distinguishable by the presence of UBAP2L. (PMID:25185265)
• These results suggest that UBAP2L has a key role in glioma cell growth, and may act as an oncogene to promote malignant glioma development. (PMID:26310274)
• arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes. (PMID:26381755)
• UBAP2L plays a critical role in maintenance of the metastatic ability of Hepatocellular Carcinoma Cells cells via SNAIL1 Regulation and is predictive of a poor clinical outcome. (PMID:28334716)
• UBAP2L is amplified in 15% of human primary lung adenocarcinoma specimens. Such patients express higher levels of UBAP2L and show a reduction in survival when compared with those who do not have this gene amplification. (PMID:28754713)
• UBAP2L was overexpressed in HCC, and patients with high UBAP2L expression had unfavorable prognosis. (PMID:28981479)
• High UBAP2L expression is associated with breast cancer. (PMID:29196913)
• UBAP2L plays an oncogenic role in HCC, and knockdown of its expression significantly inhibits HCC growth and metastasis, which may be related to the regulation of PI3K/AKT and P53 signaling pathways by UBAP2L. (PMID:30291221)
• UBAP2L arginine methylation by PRMT1 modulates stress granule assembly. (PMID:31114027)
• Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation. (PMID:31882469)
• UBAP2L Forms Distinct Cores that Act in Nucleating Stress Granules Upstream of G3BP1. (PMID:31956030)
• Large-scale tethered function assays identify factors that regulate mRNA stability and translation. (PMID:32807991)
• Molecular Insights into the Recruiting Between UCP2 and DDX5/UBAP2L in the Metabolic Plasticity of Non-Small-Cell Lung Cancer. (PMID:34308648)
• Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells. (PMID:34823423)
• UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and are the human orthologues of yeast Def1. (PMID:35633597)
• UBAP2L-dependent coupling of PLK1 localization and stability during mitosis. (PMID:37039032)
• UBAP2L ensures homeostasis of nuclear pore complexes at the intact nuclear envelope. (PMID:38652117)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubap2l	ENSDARG00000063219
mus_musculus	Ubap2l	ENSMUSG00000042520
rattus_norvegicus	Ubap2l	ENSRNOG00000017990
drosophila_melanogaster	lig	FBGN0020279
caenorhabditis_elegans	pqn-59	WBGENE00004143

Paralogs (1): UBAP2 (ENSG00000137073)

Protein

Protein identifiers

Ubiquitin-associated protein 2-like — Q14157 (reviewed: Q14157)

Alternative names: Protein NICE-4, RNA polymerase II degradation factor UBAP2L

All UniProt accessions (10): Q14157, A0AA34QVE6, F8W726, H0Y5H6, H7C2T8, Q5VU77, Q5VU78, Q5VU79, Q5VU80, Q5VU81

UniProt curated annotations — full annotation on UniProt →

Function. Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage. Plays an important role in the activity of long-term repopulating hematopoietic stem cells (LT-HSCs). Is a regulator of stress granule assembly, required for their efficient formation. Required for proper brain development and neocortex lamination.

Subunit / interactions. Interacts with BMI1. Part of a complex consisting of UBAP2L, BMI1 and RNF2. Interacts with G3BP1 (via NTF2 domain); promoting stress granule formation.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Stress granule.

Tissue specificity. Ubiquitous.

Post-translational modifications. Acetylated.

Disease relevance. Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF) [MIM:620494] A disorder characterized by global developmental delay, speech delay, variably impaired intellectual development, behavioral abnormalities, and dysmorphic facial features. Additional features include early feeding difficulties, failure to thrive, short stature, mild visual impairment, hypotonia, seizures, and distal skeletal defects of the hands and feet. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q14157-2	1	yes
Q14157-1	2
Q14157-3	3
Q14157-4	4
Q14157-5	5

RefSeq proteins (24): NP_001120792, NP_001274744, NP_001274745, NP_001317659, NP_001362541, NP_001362543, NP_001362544, NP_001362545, NP_001362546, NP_001362547, NP_001362548, NP_001362549, NP_001362550, NP_001362551, NP_001362552, NP_001362553, NP_001362554, NP_001362555, NP_001362556, NP_001362557, NP_001362558, NP_001362559, NP_001362560, NP_055662* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009060	UBA-like_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR022166	UBAP2/Lig	Family
IPR051833	TC-DDR_regulator	Family

Pfam: PF12478

UniProt features (58 total): modified residue 24, compositionally biased region 12, region of interest 8, sequence variant 7, splice variant 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14157-F1	42.99	0.04

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 (24): 1, 187, 190, 356, 360, 410, 416, 425, 439, 454, 467, 470, 471, 477, 604, 605, 608, 609, 852, 859 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 446 (showing top): MORF_MTA1, GOBP_SINGLE_FERTILIZATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_UBE2N, MORF_RAD21, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, MARTINEZ_RB1_TARGETS_UP, MORF_SKP1A, RICKMAN_METASTASIS_DN

GO Biological Process (4): binding of sperm to zona pellucida (GO:0007339), stress granule assembly (GO:0034063), hematopoietic stem cell homeostasis (GO:0061484), positive regulation of stress granule assembly (GO:0062029)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoplasmic stress granule (GO:0010494), PcG protein complex (GO:0031519)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sperm-egg recognition	1
membraneless organelle assembly	1
homeostasis of number of cells	1
stress granule assembly	1
regulation of stress granule assembly	1
positive regulation of organelle assembly	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasmic ribonucleoprotein granule	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

4915 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBAP2L	PRRC2C	Q9Y520	789
UBAP2L	G3BP1	Q13283	780
UBAP2L	CAPRIN1	Q14444	688
UBAP2L	CSDE1	O75534	600
UBAP2L	ZP3	P21754	597
UBAP2L	PABPC1	P11940	567
UBAP2L	G3BP2	Q9UN86	567
UBAP2L	TIA1	P31483	521
UBAP2L	KLHL18	O94889	489
UBAP2L	RPTOR	Q8N122	479
UBAP2L	CRCT1	Q9UGL9	477
UBAP2L	PDZD2	O15018	446
UBAP2L	PRRC2B	Q5JSZ5	443
UBAP2L	PRMT1	Q99873	439
UBAP2L	PRRC2A	P48634	432

IntAct

133 interactions, top by confidence:

A	B	Type	Score
G3BP1	N	psi-mi:“MI:0915”(physical association)	0.980
G3BP2	N	psi-mi:“MI:0915”(physical association)	0.970
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
FXR2	UBAP2L	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
UBAP2L	rep	psi-mi:“MI:0915”(physical association)	0.660
FXR1	UBAP2L	psi-mi:“MI:0915”(physical association)	0.560
G3BP1	UBAP2L	psi-mi:“MI:0915”(physical association)	0.560
G3BP1	UBAP2L	psi-mi:“MI:0403”(colocalization)	0.560
UBAP2L	FXR1	psi-mi:“MI:0914”(association)	0.550
UBAP2L	FXR1	psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
BCOR	CBX4	psi-mi:“MI:0914”(association)	0.530
rep	SBNO1	psi-mi:“MI:0914”(association)	0.530
FMR1	ACOT7	psi-mi:“MI:0914”(association)	0.500
ZP3	UBAP2L	psi-mi:“MI:0915”(physical association)	0.490
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
UBAP2L		psi-mi:“MI:0915”(physical association)	0.370
UBE2E3	UBAP2L	psi-mi:“MI:0915”(physical association)	0.370
PLXNA2	UBAP2L	psi-mi:“MI:0915”(physical association)	0.370
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (474): UBAP2L (Affinity Capture-MS), UBAP2L (Affinity Capture-RNA), UBAP2L (Affinity Capture-MS), UBAP2L (Affinity Capture-MS), UBAP2L (Affinity Capture-MS), UBAP2L (Affinity Capture-MS), UBAP2L (Two-hybrid), HNRNPDL (Co-fractionation), UBAP2L (Co-fractionation), UBAP2L (Co-fractionation), UBAP2L (Affinity Capture-MS), UBAP2L (Synthetic Growth Defect), UBAP2L (Affinity Capture-MS), UBAP2L (Affinity Capture-Western), UBAP2L (Affinity Capture-Western)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

Diamond homologs: Q14157, Q5T6F2, Q80X50, Q86S05, Q91VX2, Q16VD3, Q290X3, Q7PMS9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
UBAP2L	“up-regulates activity”	BMI1	binding
UBAP2L	“up-regulates activity”	RNF2	binding
MAPK1	unknown	UBAP2L	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 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.

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	5	23.1×	8e-04
mRNA transport	9	18.2×	2e-06
mRNA stabilization	5	14.1×	3e-03
regulation of alternative mRNA splicing, via spliceosome	6	11.3×	3e-03
negative regulation of translation	7	10.6×	1e-03
RNA splicing	9	6.1×	3e-03
mRNA processing	10	6.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	119
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2430740	NM_014847.4(UBAP2L):c.1846C>T (p.Gln616Ter)	Pathogenic
2430934	NM_014847.4(UBAP2L):c.3168+3A>G	Pathogenic
2577918	NM_014847.4(UBAP2L):c.88C>T (p.Gln30Ter)	Pathogenic
2577919	NM_014847.4(UBAP2L):c.562G>T (p.Gly188Ter)	Pathogenic
2577920	NM_014847.4(UBAP2L):c.590+1G>A	Pathogenic
3767876	NM_014847.4(UBAP2L):c.1964dup (p.Leu656fs)	Pathogenic
4601184	NM_014847.4(UBAP2L):c.2558dup (p.Ala854fs)	Pathogenic
854506	NM_014847.4(UBAP2L):c.2926_2927del (p.Thr976fs)	Pathogenic
3341088	NM_014847.4(UBAP2L):c.1554del (p.Phe518fs)	Likely pathogenic
3775286	NM_014847.4(UBAP2L):c.2968C>T (p.Gln990Ter)	Likely pathogenic
4601188	NM_014847.4(UBAP2L):c.2442G>A (p.Pro814=)	Likely pathogenic
4755533	NM_014847.4(UBAP2L):c.1986_1987del (p.Ala663fs)	Likely pathogenic
4849231	NM_014847.4(UBAP2L):c.1965del (p.Leu656fs)	Likely pathogenic

SpliceAI

3823 predictions. Top by Δscore:

Variant	Effect	Δscore
1:154227277:CCTA:C	acceptor_loss	1.0000
1:154227280:A:G	acceptor_loss	1.0000
1:154227360:G:GG	donor_gain	1.0000
1:154228613:A:AG	acceptor_gain	1.0000
1:154228613:AGTT:A	acceptor_gain	1.0000
1:154228614:G:GG	acceptor_gain	1.0000
1:154228614:GTT:G	acceptor_gain	1.0000
1:154228614:GTTG:G	acceptor_gain	1.0000
1:154228708:G:GT	donor_gain	1.0000
1:154228709:A:T	donor_gain	1.0000
1:154228712:G:GT	donor_gain	1.0000
1:154234756:GAGT:G	donor_gain	1.0000
1:154234758:GT:G	donor_gain	1.0000
1:154236553:A:AG	acceptor_gain	1.0000
1:154236554:T:G	acceptor_gain	1.0000
1:154236607:ATGGG:A	donor_gain	1.0000
1:154236609:GGG:G	donor_gain	1.0000
1:154236610:GG:G	donor_gain	1.0000
1:154236610:GGG:G	donor_gain	1.0000
1:154236611:GG:G	donor_gain	1.0000
1:154236612:G:C	donor_loss	1.0000
1:154236612:G:GG	donor_gain	1.0000
1:154236613:TAA:T	donor_loss	1.0000
1:154237022:A:AG	acceptor_gain	1.0000
1:154237023:G:GG	acceptor_gain	1.0000
1:154237023:GAAC:G	acceptor_gain	1.0000
1:154237132:GACGA:G	donor_gain	1.0000
1:154237133:ACGA:A	donor_gain	1.0000
1:154237134:CGA:C	donor_gain	1.0000
1:154237134:CGAGT:C	donor_loss	1.0000

AlphaMissense

7034 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154227295:A:C	Q35P	1.000
1:154227296:A:C	Q35H	1.000
1:154227296:A:T	Q35H	1.000
1:154227298:T:C	I36T	1.000
1:154227298:T:G	I36S	1.000
1:154227300:A:G	R37G	1.000
1:154227301:G:C	R37T	1.000
1:154227302:A:C	R37S	1.000
1:154227302:A:T	R37S	1.000
1:154227304:T:C	L38P	1.000
1:154227306:G:C	A39P	1.000
1:154227310:A:C	Q40P	1.000
1:154228616:T:C	L57S	1.000
1:154228616:T:G	L57W	1.000
1:154228628:C:A	T61K	1.000
1:154228650:T:G	C68W	1.000
1:154228657:G:C	A71P	1.000
1:154228658:C:A	A71D	1.000
1:154228661:T:C	L72S	1.000
1:154228661:T:G	L72W	1.000
1:154228663:C:G	H73D	1.000
1:154228664:A:C	H73P	1.000
1:154228666:G:C	D74H	1.000
1:154228667:A:C	D74A	1.000
1:154228667:A:T	D74V	1.000
1:154228690:G:C	A82P	1.000
1:154228691:C:A	A82D	1.000
1:154228694:T:A	I83N	1.000
1:154228703:T:C	L86P	1.000
1:154228706:T:C	L87P	1.000

dbSNP variants (sampled 300 via entrez): RS1000086133 (1:154269192 TCTC>T), RS1000152606 (1:154223333 T>C), RS1000161222 (1:154243601 C>G,T), RS1000173291 (1:154270775 T>TG), RS1000212624 (1:154237302 T>C), RS1000258051 (1:154230413 C>T), RS1000260402 (1:154249780 T>G), RS1000313514 (1:154243721 G>A), RS1000368024 (1:154267452 G>A), RS1000498180 (1:154236199 G>A), RS1000513497 (1:154231459 C>T), RS1000599769 (1:154242235 A>G), RS1000601039 (1:154248242 C>T), RS1000790547 (1:154243537 T>G), RS1000900070 (1:154241895 C>T)

Disease associations

OMIM: gene MIM:616472 | disease phenotypes: MIM:620494

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies	Definitive	Autosomal dominant

Mondo (2): neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (MONDO:0957588), neurodevelopmental disorder (MONDO:0700092)

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:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000378	Cupped ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000437	Depressed nasal tip
HP:0000483	Astigmatism
HP:0000490	Deeply set eye
HP:0000505	Visual impairment
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000718	Aggressive behavior

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST006627_16	Diastolic blood pressure	2.000000e-10
GCST007603_26	Smoking initiation	1.000000e-11
GCST008103_125	Bipolar disorder	2.000000e-06
GCST010142_92	Fish- and plant-related diet	6.000000e-14
GCST010696_22	Cortical thickness (min-P)	4.000000e-10
GCST010697_50	Cortical surface area (min-P)	1.000000e-12
GCST010698_81	Subcortical volume (min-P)	1.000000e-23
GCST010699_7	Brain morphology (min-P)	1.000000e-10
GCST010700_11	Cortical thickness (MOSTest)	4.000000e-13
GCST010701_73	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_45	Subcortical volume (MOSTest)	4.000000e-10
GCST010703_276	Brain morphology (MOSTest)	2.000000e-15
GCST011703_40	Smoking initiation	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005670	smoking initiation
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

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): CHEMBL4295819 (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 5 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.49	IC50	3240	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 11 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	2178776: Inhibition of UBAP2L (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.2400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, increases palmitoylation	3
sodium arsenite	affects binding, increases reaction, decreases expression	2
cobaltous chloride	decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
ochratoxin A	increases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
2,4-decadienal	affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119029	Binding	Binding affinity to UBAP2L in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

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