LAS1L

Summary

LAS1L (LAS1 like ribosome biogenesis factor, HGNC:25726) is a protein-coding gene on chromosome Xq12, encoding Ribosomal biogenesis protein LAS1L (Q9Y4W2). Required for the synthesis of the 60S ribosomal subunit and maturation of the 28S rRNA. It is a common-essential gene (DepMap: required in 93.2% of cancer cell lines).

Enables RNA binding activity. Involved in rRNA processing. Located in nucleolus. Part of MLL1 complex. Implicated in Wilson-Turner syndrome.

Source: NCBI Gene 81887 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wilson-Turner syndrome (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 350 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 93.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_031206

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25726
Approved symbol	LAS1L
Name	LAS1 like ribosome biogenesis factor
Location	Xq12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12525, Las1
Ensembl gene	ENSG00000001497
Ensembl biotype	protein_coding
OMIM	300964
Entrez	81887

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 28 protein_coding, 13 retained_intron, 3 nonsense_mediated_decay

ENST00000374804, ENST00000374807, ENST00000374811, ENST00000469091, ENST00000484069, ENST00000676986, ENST00000677056, ENST00000677087, ENST00000677154, ENST00000677834, ENST00000677969, ENST00000677986, ENST00000678074, ENST00000678173, ENST00000678547, ENST00000678570, ENST00000678602, ENST00000678705, ENST00000678823, ENST00000678848, ENST00000678956, ENST00000679056, ENST00000679116, ENST00000679261, ENST00000679277, ENST00000867031, ENST00000867032, ENST00000867033, ENST00000867034, ENST00000867035, ENST00000867036, ENST00000867037, ENST00000911725, ENST00000911726, ENST00000911727, ENST00000911728, ENST00000911729, ENST00000911730, ENST00000911731, ENST00000971938, ENST00000971939, ENST00000971940, ENST00000971941, ENST00000971942

RefSeq mRNA: 14 — MANE Select: NM_031206 NM_001170649, NM_001170650, NM_001375328, NM_001375329, NM_001375330, NM_001375331, NM_001375332, NM_001375333, NM_001375334, NM_001375335, NM_001375336, NM_001375337, NM_001410733, NM_031206

CCDS: CCDS14381, CCDS55433, CCDS55434, CCDS94620, CCDS94621, CCDS94622

Canonical transcript exons

ENST00000374811 — 14 exons

Exon	Start	End
ENSE00000671917	65528260	65528369
ENSE00001912676	65512582	65512901
ENSE00003254375	65529594	65529878
ENSE00003325198	65533610	65533735
ENSE00003382403	65531357	65531438
ENSE00003398451	65532561	65532630
ENSE00003439639	65529212	65529258
ENSE00003477789	65524056	65524262
ENSE00003485325	65514823	65514973
ENSE00003579202	65523560	65523707
ENSE00003665711	65517987	65518465
ENSE00003671144	65524564	65524614
ENSE00003692228	65524965	65525050
ENSE00003904158	65534480	65534787

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.9774 / max 322.0710, expressed in 1820 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199490	33.7643	1820
199488	0.2132	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.66	gold quality
cerebellar hemisphere	UBERON:0002245	96.17	gold quality
cerebellar cortex	UBERON:0002129	96.05	gold quality
cerebellum	UBERON:0002037	94.71	gold quality
right frontal lobe	UBERON:0002810	94.35	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.13	gold quality
sural nerve	UBERON:0015488	93.83	gold quality
spinal cord	UBERON:0002240	92.87	gold quality
right testis	UBERON:0004534	92.26	gold quality
left testis	UBERON:0004533	91.86	gold quality
putamen	UBERON:0001874	91.84	gold quality
cingulate cortex	UBERON:0003027	91.80	gold quality
amygdala	UBERON:0001876	91.79	gold quality
endometrium epithelium	UBERON:0004811	91.77	gold quality
nucleus accumbens	UBERON:0001882	91.76	gold quality
anterior cingulate cortex	UBERON:0009835	91.74	gold quality
left ovary	UBERON:0002119	91.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.17	gold quality
primary visual cortex	UBERON:0002436	91.12	gold quality
tibial nerve	UBERON:0001323	90.98	gold quality
body of uterus	UBERON:0009853	90.88	gold quality
right ovary	UBERON:0002118	90.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.75	gold quality
lower esophagus	UBERON:0013473	90.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.71	gold quality
caudate nucleus	UBERON:0001873	90.56	gold quality
right uterine tube	UBERON:0001302	90.50	gold quality
tibial artery	UBERON:0007610	90.46	gold quality
popliteal artery	UBERON:0002250	90.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.44
E-MTAB-7381	no	232.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting LAS1L, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-564	95.85	65.01	163
HSA-MIR-8071	95.69	64.93	484

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• Data demonstrate that Las1L is essential for cell proliferation and biogenesis of the 60S ribosomal subunit. (PMID:20647540)
• Analysis of high-molecular-weight RNAs confirmed that Las1L is required for ITS2 processing,which separates the 5.8S and 25S/28S rRNAs, as 32S was found to accumulate and 12S to diminish upon Las1L depletion. (PMID:22083961)
• LAS1L interacts with PELP1, TEX10, and WDR18, the mammalian homologues of the budding yeast Rix1 complex, along with NOL9 and SENP3, to form a novel nucleolar complex that cofractionates with the 60S preribosomal subunit. (PMID:22190735)
• Recruitment of the protein complex 5FMC to Zbp-89, a zinc-finger transcription factor, affects its sumoylation status and transactivation potential.[5FMC] (PMID:22872859)
• Inhibiting beta-catenin disables nucleolar functions in triple-negative breast cancer. (PMID:33664239)
• USP36 SUMOylates Las1L and Promotes Its Function in Pre-Ribosomal RNA ITS2 Processing. (PMID:39356143)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	las1l	ENSDARG00000062457
mus_musculus	Las1l	ENSMUSG00000057421
rattus_norvegicus	Las1l	ENSRNOG00000021748
drosophila_melanogaster	CG32075	FBGN0052075
caenorhabditis_elegans	Y6B3B.9	WBGENE00012393

Protein

Protein identifiers

Ribosomal biogenesis protein LAS1L — Q9Y4W2 (reviewed: Q9Y4W2)

Alternative names: Endoribonuclease LAS1L, Protein LAS1 homolog

All UniProt accessions (9): A0A7I2V3Q3, A0A7I2V3R6, A0A7I2V4E5, A0A7I2V4V0, A0A7I2V5R7, A0A7I2V653, A0A7I2YQI7, Q9Y4W2, R4GNF7

UniProt curated annotations — full annotation on UniProt →

Function. Required for the synthesis of the 60S ribosomal subunit and maturation of the 28S rRNA. Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Required for the efficient pre-rRNA processing at both ends of internal transcribed spacer 2 (ITS2).

Subunit / interactions. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9 to form an ITS2 pre-rRNA endonuclease-kinase complex.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Cytoplasm.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic, Wilson-Turner type (WTS) [MIM:309585] A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the LAS1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y4W2-1	1	yes
Q9Y4W2-2	2
Q9Y4W2-3	3
Q9Y4W2-4	4

RefSeq proteins (14): NP_001164120, NP_001164121, NP_001362257, NP_001362258, NP_001362259, NP_001362260, NP_001362261, NP_001362262, NP_001362263, NP_001362264, NP_001362265, NP_001362266, NP_001397662, NP_112483* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007174	Las1	Family

Pfam: PF04031

UniProt features (21 total): modified residue 4, splice variant 4, compositionally biased region 4, region of interest 3, sequence variant 3, cross-link 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8FL3	ELECTRON MICROSCOPY	2.53
8FL2	ELECTRON MICROSCOPY	2.67
8FL4	ELECTRON MICROSCOPY	2.89
9DUN	ELECTRON MICROSCOPY	3.32
26LK	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4W2-F1	63.26	0.25

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 (6): 560, 617, 215, 226, 441, 523

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 232 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GNF2_MCM5, WEI_MYCN_TARGETS_WITH_E_BOX, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_MATURATION_OF_LSU_RRNA, FISCHER_DREAM_TARGETS, GNF2_ELAC2, GOBP_MATURATION_OF_5_8S_RRNA, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RIBOSOMAL_LARGE_SUBUNIT_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (3): maturation of 5.8S rRNA (GO:0000460), maturation of LSU-rRNA (GO:0000470), rRNA processing (GO:0006364)

GO Molecular Function (4): RNA binding (GO:0003723), endonuclease activity (GO:0004519), hydrolase activity (GO:0016787), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), membrane (GO:0016020), MLL1 complex (GO:0071339), Las1 complex (GO:0090730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
rRNA processing	2
nuclear lumen	2
ribosomal large subunit biogenesis	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
nucleic acid binding	1
nuclease activity	1
catalytic activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
MLL1/2 complex	1
cytosol	1
endoribonuclease complex	1
protein kinase complex	1
exoribonuclease complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAS1L	TEX10	Q9NXF1	924
LAS1L	PELP1	Q8IZL8	884
LAS1L	WDR18	Q9BV38	873
LAS1L	SENP3	Q9H4L4	842
LAS1L	NOL9	Q5SY16	729
LAS1L	IGHMBP2	P38935	479
LAS1L	ZC4H2	Q9NQZ6	477
LAS1L	CHTOP	Q9Y3Y2	476
LAS1L	KLHL15	Q96M94	461
LAS1L	NUCLEOLIN	P19338	438
LAS1L	EXOSC3	Q9NQT5	432
LAS1L	SOX2	P48431	405
LAS1L	RLIM	Q9NVW2	404
LAS1L	SFRP5	Q5T4F7	401
LAS1L	TTLL4	Q14679	400

IntAct

164 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
SENP3	NPM1	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
NOL9	SENP3	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
NOL9	IPO5	psi-mi:“MI:0914”(association)	0.530
WDR18	NOL9	psi-mi:“MI:0914”(association)	0.530
IPO5	SLC27A2	psi-mi:“MI:0914”(association)	0.530
LAS1L	rep	psi-mi:“MI:0915”(physical association)	0.510
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
RPGRIP1L	LAS1L	psi-mi:“MI:0915”(physical association)	0.400
SLC16A10	LAS1L	psi-mi:“MI:0915”(physical association)	0.400
PELP1	LAS1L	psi-mi:“MI:0915”(physical association)	0.400
LAS1L	E7	psi-mi:“MI:0915”(physical association)	0.370
LAS1L	rep	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PB1	HAX1	psi-mi:“MI:0914”(association)	0.350
PB1	IPO5	psi-mi:“MI:0914”(association)	0.350
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB2	HAX1	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (265): LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS), LAS1L (Reconstituted Complex), LAS1L (Affinity Capture-MS), NOL9 (Co-fractionation), PELP1 (Co-fractionation), TEX10 (Co-fractionation), WDR18 (Co-fractionation), LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS), LAS1L (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0FKI7, A1A5R8, A2AHC3, A2BE28, A5WUN7, A8DZJ1, B7ZS37, D3Z6S9, D3Z8E6, O55036, O60281, O75113, P54274, P62932, P70278, Q08AD1, Q13129, Q16533, Q2T9I9, Q3UMB5, Q5BLK4, Q5H9M0, Q5T4T6, Q5T5Y3, Q5VYS8, Q640U0, Q641E3, Q6DRL4, Q6IRN6, Q6PUR7, Q7Z2Z1, Q7Z7J5, Q86WZ0, Q8BQ33, Q8IZM8, Q8K0S9, Q8NEM2, Q8TEV9

Diamond homologs: A2BE28, Q9Y4W2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LAS1L	“up-regulates activity”	“Rix1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 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
PD-L1(CD274) glycosylation and translocation to plasma membrane	5	19.8×	8e-04
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	5	12.8×	3e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	6	10.5×	2e-03
Maturation of spike protein	5	10.1×	6e-03
Maturation of DENV proteins	6	9.7×	3e-03
AUF1 (hnRNP D0) binds and destabilizes mRNA	5	9.5×	7e-03
Proteasome assembly	6	9.3×	3e-03
Degradation of DVL	5	9.1×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
activation of innate immune response	5	15.1×	4e-03
ribosomal large subunit biogenesis	5	13.9×	4e-03
negative regulation of viral genome replication	5	11.8×	7e-03
ribosomal small subunit biogenesis	7	10.0×	3e-03
rRNA processing	10	8.9×	2e-04
DNA damage response	13	4.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	144
Likely benign	76
Benign	20

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
253106	NM_031206.7(LAS1L):c.806C>G (p.Ala269Gly)	Pathogenic
208745	NM_031206.7(LAS1L):c.1430G>A (p.Ser477Asn)	Likely pathogenic
384751	NM_031206.7(LAS1L):c.2047C>T (p.Gln683Ter)	Likely pathogenic
4759342	NM_031206.7(LAS1L):c.2082dup (p.Leu697fs)	Likely pathogenic
666263	NM_031206.7(LAS1L):c.1237G>A (p.Gly413Arg)	Likely pathogenic

SpliceAI

3426 predictions. Top by Δscore:

Variant	Effect	Δscore
X:65489391:G:GT	donor_gain	1.0000
X:65497118:T:TA	acceptor_gain	1.0000
X:65497121:A:AG	acceptor_gain	1.0000
X:65497122:T:G	acceptor_gain	1.0000
X:65497130:A:G	acceptor_gain	1.0000
X:65497267:TACAG:T	donor_loss	1.0000
X:65497268:ACAG:A	donor_loss	1.0000
X:65497269:CAGGT:C	donor_loss	1.0000
X:65497270:AGGT:A	donor_loss	1.0000
X:65497271:GG:G	donor_loss	1.0000
X:65497272:G:C	donor_loss	1.0000
X:65497273:T:A	donor_loss	1.0000
X:65499183:G:GT	donor_gain	1.0000
X:65499186:G:GT	donor_gain	1.0000
X:65499200:A:T	donor_gain	1.0000
X:65499234:G:GG	donor_gain	1.0000
X:65499272:G:GG	donor_gain	1.0000
X:65499986:TATGG:T	donor_loss	1.0000
X:65499987:ATGG:A	donor_loss	1.0000
X:65499988:TGG:T	donor_loss	1.0000
X:65499989:GGTG:G	donor_loss	1.0000
X:65499990:G:GA	donor_loss	1.0000
X:65499991:T:G	donor_loss	1.0000
X:65499992:GAG:G	donor_loss	1.0000
X:65514816:CACT:C	donor_loss	1.0000
X:65514819:TCACT:T	donor_loss	1.0000
X:65514820:CA:C	donor_loss	1.0000
X:65514821:A:AC	donor_gain	1.0000
X:65514821:A:T	donor_loss	1.0000
X:65514821:ACT:A	donor_gain	1.0000

AlphaMissense

4842 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:65524092:A:G	W422R	0.999
X:65524092:A:T	W422R	0.999
X:65524212:A:G	W382R	0.999
X:65524212:A:T	W382R	0.999
X:65529854:A:G	L180P	0.999
X:65525006:G:C	P334R	0.998
X:65525006:G:T	P334H	0.998
X:65525014:G:C	F331L	0.998
X:65525014:G:T	F331L	0.998
X:65525016:A:G	F331L	0.998
X:65529866:A:T	V176D	0.998
X:65531393:G:C	H160D	0.998
X:65531410:A:G	L154P	0.998
X:65532619:A:G	L125P	0.998
X:65532627:A:C	F122L	0.998
X:65532627:A:T	F122L	0.998
X:65532629:A:G	F122L	0.998
X:65533625:C:T	G116D	0.998
X:65533691:A:G	L94P	0.998
X:65524079:A:G	L426P	0.997
X:65524214:A:G	F381S	0.997
X:65525015:A:G	F331S	0.997
X:65529840:A:G	W185R	0.997
X:65529840:A:T	W185R	0.997
X:65529858:A:G	W179R	0.997
X:65529858:A:T	W179R	0.997
X:65531357:C:G	G172R	0.997
X:65531362:C:G	R170P	0.997
X:65531366:A:G	C169R	0.997
X:65531408:G:T	R155S	0.997

dbSNP variants (sampled 300 via entrez): RS1000033310 (X:65522626 T>C), RS1000072144 (X:65531902 C>A), RS1000085360 (X:65522194 C>A,T), RS1000298476 (X:65530496 T>C), RS1000359497 (X:65531441 G>A), RS1000452689 (X:65522410 G>A), RS1000587270 (X:65513782 C>T), RS1000635272 (X:65513278 C>T), RS1000892447 (X:65533938 G>A), RS1000974402 (X:65525227 G>C), RS1001238543 (X:65521022 C>T), RS1001523955 (X:65521236 T>C), RS1001562286 (X:65516869 A>G), RS1001586183 (X:65522092 A>T), RS1001638667 (X:65521642 G>C)

Disease associations

OMIM: gene MIM:300964 | disease phenotypes: MIM:309585

GenCC curated gene-disease

Disease	Classification	Inheritance
Wilson-Turner syndrome	Strong	X-linked
spinal muscular atrophy with respiratory distress type 2	Supportive	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked syndromic intellectual disability	Limited	XL

Mondo (5): Wilson-Turner syndrome (MONDO:0010665), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), spinal muscular atrophy with respiratory distress type 2 (MONDO:0018450)

Orphanet (3): Wilson-Turner syndrome (Orphanet:3459), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000336	Prominent supraorbital ridges
HP:0000347	Micrognathia
HP:0000455	Broad nasal tip
HP:0000490	Deeply set eye
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000574	Thick eyebrow
HP:0000712	Emotional lability
HP:0000750	Delayed speech and language development
HP:0000771	Gynecomastia
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001328	Specific learning disability
HP:0001344	Absent speech
HP:0001419	X-linked recessive inheritance
HP:0001513	Obesity
HP:0001761	Pes cavus
HP:0001763	Pes planus
HP:0001773	Short foot
HP:0001956	Truncal obesity
HP:0001999	Abnormal facial shape
HP:0002465	Poor speech
HP:0004322	Short stature
HP:0008551	Microtia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

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
C536708	Wilson-Turner X-linked mental retardation syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724634 (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
6.57	IC50	270	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	2178791: Inhibition of LAS1L (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.2700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Lead	affects expression, decreases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	affects expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Thiram	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
CHEMBL5697521	Binding	Inhibition of LAS1L (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

Clinical trials (associated diseases)

300 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,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
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
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder