MAST1

Summary

MAST1 (microtubule associated serine/threonine kinase 1, HGNC:19034) is a protein-coding gene on chromosome 19p13.13, encoding Microtubule-associated serine/threonine-protein kinase 1 (Q9Y2H9). Microtubule-associated protein essential for correct brain development.

This gene is a member of the microtubule-associated serine/threonine kinase (MAST) family. The protein encoded by this gene has an N-terminal serine/threonine kinase domain followed by a postsynaptic density protein-95/discs large/zona occludens-1 (PDZ) domain. In mouse and rat, the orthologous protein associates with the cytoskeleton and can bind both beta-2-syntrophin and neuronal nitric oxide synthase (nNOS) through its PDZ domain. In mouse and rat, this protein also co-localizes with dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in the vascular endothelium of the central nervous system.

Source: NCBI Gene 22983 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (Strong, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 590 total — 4 pathogenic, 9 likely-pathogenic
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19034
Approved symbol	MAST1
Name	microtubule associated serine/threonine kinase 1
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	SAST, KIAA0973
Ensembl gene	ENSG00000105613
Ensembl biotype	protein_coding
OMIM	612256
Entrez	22983

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000251472, ENST00000585791, ENST00000589040, ENST00000590204, ENST00000590553, ENST00000590883, ENST00000591495, ENST00000592713, ENST00000699746

RefSeq mRNA: 1 — MANE Select: NM_014975 NM_014975

CCDS: CCDS32921

Canonical transcript exons

ENST00000251472 — 26 exons

Exon	Start	End
ENSE00000682711	12867730	12867977
ENSE00000682713	12867474	12867652
ENSE00000682715	12866653	12866762
ENSE00000682719	12865717	12865818
ENSE00000682727	12858531	12858739
ENSE00000682741	12843529	12843607
ENSE00000836355	12847848	12848057
ENSE00000836356	12851934	12852035
ENSE00000836357	12852115	12852247
ENSE00000836360	12868643	12868849
ENSE00001263268	12873609	12874952
ENSE00001650833	12865980	12866102
ENSE00001676961	12865316	12865481
ENSE00001741199	12865046	12865178
ENSE00002893290	12838515	12838655
ENSE00003507675	12840446	12840534
ENSE00003512673	12871036	12871172
ENSE00003556069	12852328	12852395
ENSE00003566399	12847612	12847687
ENSE00003619245	12847290	12847450
ENSE00003639356	12840991	12841066
ENSE00003657131	12870824	12870946
ENSE00003672837	12873324	12873511
ENSE00003684333	12864809	12864947
ENSE00003685068	12858362	12858441
ENSE00003687101	12869066	12869295

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 98.53.

FANTOM5 (CAGE): breadth broad, TPM avg 11.1149 / max 660.8152, expressed in 738 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174036	9.4039	682
174035	1.3530	359
174034	0.2188	120
174033	0.1392	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.53	gold quality
cerebellar hemisphere	UBERON:0002245	98.12	gold quality
cerebellar cortex	UBERON:0002129	97.96	gold quality
cortical plate	UBERON:0005343	97.65	gold quality
right frontal lobe	UBERON:0002810	96.28	gold quality
cerebellum	UBERON:0002037	95.54	gold quality
ganglionic eminence	UBERON:0004023	93.94	gold quality
anterior cingulate cortex	UBERON:0009835	92.64	gold quality
cingulate cortex	UBERON:0003027	92.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.19	gold quality
paraflocculus	UBERON:0005351	92.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.23	gold quality
prefrontal cortex	UBERON:0000451	91.06	gold quality
neocortex	UBERON:0001950	89.87	gold quality
frontal pole	UBERON:0002795	89.73	gold quality
frontal cortex	UBERON:0001870	89.46	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.45	gold quality
adenohypophysis	UBERON:0002196	88.18	gold quality
pituitary gland	UBERON:0000007	87.93	gold quality
cerebral cortex	UBERON:0000956	87.90	gold quality
hypothalamus	UBERON:0001898	87.02	gold quality
amygdala	UBERON:0001876	86.20	gold quality
ventricular zone	UBERON:0003053	85.38	gold quality
brain	UBERON:0000955	84.89	gold quality
central nervous system	UBERON:0001017	84.57	gold quality
forebrain	UBERON:0001890	84.40	gold quality
telencephalon	UBERON:0001893	84.20	gold quality
Ammon’s horn	UBERON:0001954	83.68	gold quality
primary visual cortex	UBERON:0002436	83.19	gold quality
superior frontal gyrus	UBERON:0002661	82.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.66

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 11)

• Discusses cloning of Sast, the mouse ortholog of human MAST1. (PMID:10404183)
• Discusses cloning of Sast124, the rat ortholog of MAST1. (PMID:12614677)
• Overexpression of MAST1 or MAST2 gene fusions has a proliferative effect both in vitro and in vivo in breast cancer cell lines. (PMID:22101766)
• This report showed that de novo MAST1 substitutions are present in patients with autism and microcephaly, raising the prospect that mutations in this gene give rise to a spectrum of neurodevelopmental diseases. (PMID:30449657)
• Through a proteomics screen, we identified the heat shock protein 90 B (hsp90B) chaperone as a direct MAST1 binding partner essential for its stabilization. Targeting hsp90B sensitized cancer cells to cisplatin predominantly through MAST1 destabilization. Mechanistically, interaction of hsp90B with MAST1 blocked ubiquitination of MAST1 at lysines 317 and 545. (PMID:31449053)
• Evaluating the Role of MAST1 as an Intellectual Disability Disease Gene: Identification of a Novel De Novo Variant in a Patient with Developmental Disabilities. (PMID:31721002)
• MAST1 modulates neuronal differentiation and cell cycle exit via P27 in neuroblastoma cells. (PMID:32291963)
• Cisplatin-mediated activation of glucocorticoid receptor induces platinum resistance via MAST1. (PMID:34400618)
• Mast1 mediates radiation-induced gastric injury via the P38 MAPK pathway. (PMID:34774870)
• CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA. (PMID:38331765)
• USP28 promotes tumorigenesis and cisplatin resistance by deubiquitinating MAST1 protein in cancer cells. (PMID:38498222)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	mast1a	ENSDARG00000027497
danio_rerio	mast1b	ENSDARG00000088789
mus_musculus	Mast1	ENSMUSG00000053693
rattus_norvegicus	MAST1	ENSRNOG00000003469
drosophila_melanogaster	CG32944	FBGN0052944
drosophila_melanogaster	dop	FBGN0267390
caenorhabditis_elegans		WBGENE00002192
caenorhabditis_elegans	wts-1	WBGENE00007047
caenorhabditis_elegans		WBGENE00010838
caenorhabditis_elegans		WBGENE00011992

Paralogs (13): MAST4 (ENSG00000069020), MAST2 (ENSG00000086015), MAST3 (ENSG00000099308), SGK2 (ENSG00000101049), SGK3 (ENSG00000104205), DMPK (ENSG00000104936), SGK1 (ENSG00000118515), MASTL (ENSG00000120539), LATS1 (ENSG00000131023), LATS2 (ENSG00000150457), STK32B (ENSG00000152953), STK32C (ENSG00000165752), STK32A (ENSG00000169302)

Protein

Protein identifiers

Microtubule-associated serine/threonine-protein kinase 1 — Q9Y2H9 (reviewed: Q9Y2H9)

Alternative names: Syntrophin-associated serine/threonine-protein kinase

All UniProt accessions (4): A0A8V8TQG4, Q9Y2H9, K7EJI7, K7EME4

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-associated protein essential for correct brain development. Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins.

Subunit / interactions. Interacts with the microtubules. Part of a low affinity complex that associates with, but is distinct from, the postsynaptic density. Interacts with SNTB2.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Cell projection. Axon. Dendrite.

Tissue specificity. Expressed in fetal brain.

Disease relevance. Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) [MIM:618273] An autosomal dominant neurodevelopmental disorder with onset in infancy. MCCCHCM is characterized by global developmental delay, impaired intellectual development, poor or absent speech, unsteady gait, ataxia, inability to walk, and variable brain abnormalities. Seizures and autistic features are observed in some patients. Brain imaging findings include an enlarged corpus callosum in the absence of megalencephaly, cerebellar hypoplasia, ventricular dilation, gyral abnormalities, and cortical malformations. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.

RefSeq proteins (1): NP_055790* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR001478	PDZ	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015022	MAST_pre-PK_dom	Domain
IPR023142	MAST_pre-PK_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR037711	MAST	Domain
IPR041489	PDZ_6	Domain
IPR050236	Ser_Thr_kinase_AGC	Family

Pfam: PF00069, PF08926, PF17820

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (66 total): compositionally biased region 16, sequence variant 12, region of interest 9, modified residue 9, helix 6, strand 6, domain 3, binding site 2, chain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3PS4	X-RAY DIFFRACTION	1.85
2M9X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2H9-F1	54.19	0.17

Functional residue map

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

Catalytic / active sites (1): 497 (proton acceptor)

Ligand- & substrate-binding residues (2): 380–388; 403

Post-translational modifications (9): 90, 139, 167, 346, 351, 687, 893, 952, 1413

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): MYOGENIN_Q6, AP4_Q6, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, SOX9_B1, HEN1_01, NRF2_Q4, GOBP_HEAD_DEVELOPMENT, GOCC_NEURON_PROJECTION, SCHLOSSER_SERUM_RESPONSE_AUGMENTED_BY_MYC, KAYO_AGING_MUSCLE_UP, JAZAERI_BREAST_CANCER_BRCA1_VS_BRCA2_DN, ATGTACA_MIR493, MARSON_BOUND_BY_E2F4_UNSTIMULATED, E2A_Q2

GO Biological Process (5): protein phosphorylation (GO:0006468), cytoskeleton organization (GO:0007010), brain development (GO:0007420), intracellular signal transduction (GO:0035556), developmental process (GO:0032502)

GO Molecular Function (11): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), microtubule binding (GO:0008017), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (10): plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), axon (GO:0030424), dendrite (GO:0030425), neuron projection (GO:0043005), neuronal cell body (GO:0043025), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
protein kinase activity	2
neuron projection	2
phosphorylation	1
protein modification process	1
organelle organization	1
central nervous system development	1
animal organ development	1
head development	1
signal transduction	1
biological_process	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
cytoskeleton	1
dendritic tree	1
plasma membrane bounded cell projection	1
somatodendritic compartment	1
cell body	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAST1	MAGI2	Q86UL8	761
MAST1	SNTB2	Q13425	671
MAST1	PTEN	P60484	528
MAST1	NEK2	P51955	406
MAST1	CACNG2	Q9Y698	386
MAST1	MAGI3	Q5TCQ9	368
MAST1	S1PR2	O95136	356
MAST1	ARPP19	P56211	355
MAST1	DLG1	Q12959	353
MAST1	CABIN1	Q9Y6J0	347
MAST1	NOP53	Q9NZM5	341
MAST1	NHERF2	Q15599	341
MAST1	SPANXN2	Q5MJ10	336
MAST1	UBE2E3	Q969T4	336
MAST1	GOPC	Q9HD26	327

IntAct

423 interactions, top by confidence:

A	B	Type	Score
MAST1	YWHAB	psi-mi:“MI:0914”(association)	0.640
EGFR	MAST1	psi-mi:“MI:0915”(physical association)	0.630
MAST1	EGFR	psi-mi:“MI:0915”(physical association)	0.630
MAST1	HSPA5	psi-mi:“MI:0915”(physical association)	0.610
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
MAST1	ACE2	psi-mi:“MI:0915”(physical association)	0.610
PTEN	MAST1	psi-mi:“MI:0407”(direct interaction)	0.610
RPS6KA1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.610
MAST1	E6	psi-mi:“MI:0407”(direct interaction)	0.610
MAST1	E6	psi-mi:“MI:0915”(physical association)	0.610
E6	MAST1	psi-mi:“MI:0407”(direct interaction)	0.610
MAST1	PTEN	psi-mi:“MI:0915”(physical association)	0.610
MAST1	PTEN	psi-mi:“MI:0407”(direct interaction)	0.610
ACE2	MAST1	psi-mi:“MI:0407”(direct interaction)	0.610
SLC4A7	MAST1	psi-mi:“MI:0407”(direct interaction)	0.590
MCC	MAST1	psi-mi:“MI:0407”(direct interaction)	0.590
CTNNB1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.590
ACOT8	MAST1	psi-mi:“MI:0407”(direct interaction)	0.590
MAST1	ECSIT	psi-mi:“MI:0915”(physical association)	0.550
EXOSC1	MAST1	psi-mi:“MI:0915”(physical association)	0.550
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
E6	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
NET1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (244): YWHAB (Affinity Capture-MS), YWHAE (Affinity Capture-MS), YWHAH (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), MAST1 (Affinity Capture-RNA), MAST1 (Protein-peptide), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-Western), HSP90AA1 (Affinity Capture-Western), MAST1 (Affinity Capture-Western), MAST1 (Affinity Capture-Western), STUB1 (Affinity Capture-MS), MAST1 (Affinity Capture-Western), HSP90AB1 (Reconstituted Complex), MAST1 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2JUG7, A1L390, E9Q0S6, O08774, O14924, O15085, O43182, O54834, O54960, O60307, O75052, P57095, Q13009, Q3U1V8, Q3U214, Q3UHC7, Q4VAC9, Q5DU25, Q5JU85, Q5RBI7, Q5SXA9, Q5VWQ8, Q60610, Q64512, Q6AX33, Q6DN90, Q6NXJ0, Q6P0Q8, Q6P1I6, Q6ZMN7, Q76G19, Q76LL6, Q76M68, Q7T2V3, Q810W7, Q8CGE9, Q8IX03, Q8R0S2, Q8R4H2, Q8WYP3

Diamond homologs: A2VDV2, A8WVU9, A8XJL7, E9PSL7, F4HPN2, F4HYG2, F4J6F6, M3TYT0, O01583, O13310, O14578, O15021, O45797, O54874, O60307, O75116, O77819, O94487, O95835, P00517, P05131, P05383, P0C1B1, P12688, P17612, P18961, P22204, P22694, P25321, P27791, P31034, P32328, P36887, P38679, P38938, P49025, P53894, P54265, P54644, P68180

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAST1	down-regulates	PTEN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
Signaling by NTRKs	8	11.1×	4e-04
Signaling by NTRK1 (TRKA)	7	10.5×	1e-03
Transcriptional and post-translational regulation of MITF-M expression and activity	6	8.2×	8e-03
Signaling by Receptor Tyrosine Kinases	11	4.3×	7e-03
Transport of small molecules	16	3.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
monoatomic ion transport	10	9.0×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	9
Uncertain significance	317
Likely benign	191
Benign	34

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1319774	NM_014975.3(MAST1):c.873C>A (p.Cys291Ter)	Pathogenic
1698956	NM_014975.3(MAST1):c.1568T>C (p.Leu523Pro)	Pathogenic
599360	NM_014975.3(MAST1):c.832_834del (p.Leu279del)	Pathogenic
599361	NM_014975.3(MAST1):c.1549G>A (p.Gly517Ser)	Pathogenic
1679266	NM_014975.3(MAST1):c.1580C>A (p.Thr527Asn)	Likely pathogenic
1805144	NM_014975.3(MAST1):c.1594G>C (p.Glu532Gln)	Likely pathogenic
2501671	NM_014975.3(MAST1):c.1298T>C (p.Phe433Ser)	Likely pathogenic
2580895	NM_014975.3(MAST1):c.3530C>T (p.Pro1177Leu)	Likely pathogenic
2582570	NM_014975.3(MAST1):c.377C>A (p.Thr126Lys)	Likely pathogenic
3256757	NM_014975.3(MAST1):c.1762T>G (p.Phe588Val)	Likely pathogenic
3384036	NM_014975.3(MAST1):c.3539T>G (p.Leu1180Arg)	Likely pathogenic
4531705	NM_014975.3(MAST1):c.1486C>T (p.Arg496Cys)	Likely pathogenic
599359	NM_014975.3(MAST1):c.826AAG[1] (p.Lys277del)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

10130 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12843545:T:A	W89R	1.000
19:12843545:T:C	W89R	1.000
19:12843547:G:C	W89C	1.000
19:12843547:G:T	W89C	1.000
19:12843572:G:C	G98R	1.000
19:12843573:G:A	G98D	1.000
19:12843575:T:C	Y99H	1.000
19:12843579:G:A	G100D	1.000
19:12843586:C:A	N102K	1.000
19:12843586:C:G	N102K	1.000
19:12843593:A:C	S105R	1.000
19:12843595:T:A	S105R	1.000
19:12843595:T:G	S105R	1.000
19:12847443:A:C	S161R	1.000
19:12847445:C:A	S161R	1.000
19:12847445:C:G	S161R	1.000
19:12858405:T:C	F374S	1.000
19:12858423:T:A	I380K	1.000
19:12858425:A:C	S381R	1.000
19:12858427:C:A	S381R	1.000
19:12858427:C:G	S381R	1.000
19:12858536:T:A	V388D	1.000
19:12858575:C:A	A401D	1.000
19:12858581:A:T	K403I	1.000
19:12858582:A:C	K403N	1.000
19:12858582:A:T	K403N	1.000
19:12858611:G:C	R413P	1.000
19:12858715:T:C	C448R	1.000
19:12858717:C:G	C448W	1.000
19:12865048:T:C	L503P	1.000

dbSNP variants (sampled 300 via entrez): RS1000101137 (19:12855013 T>G), RS1000101908 (19:12873257 G>A,T), RS1000154378 (19:12873553 G>C), RS1000163967 (19:12837150 T>A), RS1000303864 (19:12857605 G>A,C), RS1000809581 (19:12837437 A>C), RS1000854048 (19:12844313 A>G), RS1000859936 (19:12849096 A>T), RS1000889904 (19:12863631 T>C), RS1000913897 (19:12849305 T>C), RS1000955706 (19:12862515 T>C), RS1001102333 (19:12871834 T>C), RS1001129317 (19:12863144 G>C), RS1001158221 (19:12837125 G>A), RS1001180151 (19:12862886 C>T)

Disease associations

OMIM: gene MIM:612256 | disease phenotypes: MIM:618273

GenCC curated gene-disease

Disease	Classification	Inheritance
mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations	Strong	Autosomal dominant

Mondo (2): mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MONDO:0032648), intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST004611_150	High light scatter reticulocyte count	4.000000e-16
GCST004612_97	High light scatter reticulocyte percentage of red cells	1.000000e-21
GCST004625_208	Monocyte count	9.000000e-10
GCST005316_235	Intelligence (MTAG)	3.000000e-08
GCST005993_20	Mean corpuscular hemoglobin	4.000000e-26
GCST005996_7	Red blood cell count	5.000000e-19
GCST90002386_67	High light scatter reticulocyte percentage of red cells	5.000000e-64
GCST90002387_45	Immature fraction of reticulocytes	3.000000e-18
GCST90002390_525	Mean corpuscular hemoglobin	1.000000e-20
GCST90002392_63	Mean corpuscular volume	3.000000e-33
GCST90002393_643	Monocyte count	2.000000e-13
GCST90002396_19	Mean reticulocyte volume	2.000000e-15
GCST90002397_188	Mean spheric corpuscular volume	3.000000e-17
GCST90002406_487	Reticulocyte fraction of red cells	1.000000e-17

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0005091	monocyte count
EFO:0004337	intelligence
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1163128 (SINGLE PROTEIN), CHEMBL3038500 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 135,412 (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
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL296468	BMS-387032	1	2,075

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — MAST family

ChEMBL bioactivities

17 potent at pChembl≥5 of 17 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.72	Kd	19	nM	LESTAURTINIB
7.40	Kd	40	nM	DOVITINIB
6.82	Kd	150	nM	STAUROSPORINE
6.72	Kd	190	nM	MIDOSTAURIN
6.70	Kd	200	nM	SUNITINIB
6.52	Kd	300	nM	SU-014813
6.46	Kd	350	nM	BOSUTINIB
6.28	Kd	520	nM	RUXOLITINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.48	Kd	3300	nM	TAE-684
5.34	Kd	4600	nM	NINTEDANIB
5.26	Kd	5500	nM	NERATINIB
5.21	Kd	6200	nM	BMS-387032

PubChem BioAssay actives

14 with measured affinity, of 126 total; 12 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
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507611: Binding affinity to MAST1	kd	0.0190	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625091: Binding constant for MAST1 kinase domain	kd	0.0400	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	625091: Binding constant for MAST1 kinase domain	kd	0.1500	uM
Midostaurin	625091: Binding constant for MAST1 kinase domain	kd	0.1900	uM
Sunitinib	507611: Binding affinity to MAST1	kd	0.2000	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625091: Binding constant for MAST1 kinase domain	kd	0.3000	uM
Bosutinib	625091: Binding constant for MAST1 kinase domain	kd	0.3500	uM
Ruxolitinib	625091: Binding constant for MAST1 kinase domain	kd	0.5200	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625091: Binding constant for MAST1 kinase domain	kd	3.3000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625091: Binding constant for MAST1 kinase domain	kd	4.6000	uM
Neratinib	625091: Binding constant for MAST1 kinase domain	kd	5.5000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	625091: Binding constant for MAST1 kinase domain	kd	6.2000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	2
Valproic Acid	increases methylation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	increases expression	1
titanium dioxide	increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
K 7174	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Lead	affects splicing	1
Niclosamide	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Gold Compounds	increases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

76 unique, capped per target: 76 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1166070	Binding	Inhibition of MAST1 at 1 uM	Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SX20	HAP1 MAST1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders