MAST3

Summary

MAST3 (microtubule associated serine/threonine kinase 3, HGNC:19036) is a protein-coding gene on chromosome 19p13.11, encoding Microtubule-associated serine/threonine-protein kinase 3 (O60307).

Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in cytoskeleton organization and intracellular signal transduction. Predicted to be located in cytoplasm. Implicated in developmental and epileptic encephalopathy 108.

Source: NCBI Gene 23031 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy 108 (Strong, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 302 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes
• MANE Select transcript: NM_001393504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19036
Approved symbol	MAST3
Name	microtubule associated serine/threonine kinase 3
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0561
Ensembl gene	ENSG00000099308
Ensembl biotype	protein_coding
OMIM	612258
Entrez	23031

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000262811, ENST00000601226, ENST00000608648, ENST00000609076, ENST00000609494, ENST00000687212, ENST00000697700, ENST00000697701, ENST00000697702, ENST00000704363, ENST00000893415, ENST00000893416, ENST00000893417

RefSeq mRNA: 22 — MANE Select: NM_001393504 NM_001393501, NM_001393502, NM_001393503, NM_001393504, NM_001393505, NM_001393506, NM_001393507, NM_001393508, NM_001393509, NM_001393510, NM_001393511, NM_001393512, NM_001393513, NM_001393514, NM_001393515, NM_001393516, NM_001393517, NM_001393518, NM_001393519, NM_001393520, NM_001393521, NM_015016

CCDS: CCDS46014, CCDS92564, CCDS92565, CCDS92566

Canonical transcript exons

ENST00000687212 — 28 exons

Exon	Start	End
ENSE00000690133	18130494	18130702
ENSE00000871082	18123939	18124148
ENSE00000871083	18124265	18124366
ENSE00000871085	18128866	18128951
ENSE00000871086	18134579	18134711
ENSE00001056295	18128400	18128458
ENSE00001056296	18143763	18144007
ENSE00001056300	18141882	18142015
ENSE00001056302	18123580	18123655
ENSE00001056303	18139015	18139124
ENSE00001056304	18144466	18144693
ENSE00001056305	18147443	18147624
ENSE00001056306	18121853	18121922
ENSE00001056308	18122673	18122751
ENSE00001056310	18123217	18123374
ENSE00001056311	18124642	18124774
ENSE00001113485	18135740	18135841
ENSE00001113486	18137239	18137361
ENSE00001125565	18121685	18121773
ENSE00001184245	18107587	18107618
ENSE00001184250	18097778	18097831
ENSE00001661571	18131909	18132047
ENSE00001773958	18134817	18134982
ENSE00003926547	18149191	18151687
ENSE00003928696	18146881	18147044
ENSE00003937096	18110652	18110741
ENSE00003971468	18145003	18145229
ENSE00003991506	18145743	18145865

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2895 / max 524.7137, expressed in 1675 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174583	6.6746	991
174585	3.2438	970
174587	2.7098	1212
174584	0.4828	148
174586	0.1330	31
174595	0.0456	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.31	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.27	gold quality
middle frontal gyrus	UBERON:0002702	98.04	gold quality
middle temporal gyrus	UBERON:0002771	98.03	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.21	gold quality
orbitofrontal cortex	UBERON:0004167	96.42	gold quality
entorhinal cortex	UBERON:0002728	96.41	gold quality
CA1 field of hippocampus	UBERON:0003881	96.34	gold quality
superior frontal gyrus	UBERON:0002661	96.18	gold quality
parietal lobe	UBERON:0001872	95.70	gold quality
postcentral gyrus	UBERON:0002581	95.66	gold quality
lateral globus pallidus	UBERON:0002476	95.62	gold quality
occipital lobe	UBERON:0002021	94.52	gold quality
primary visual cortex	UBERON:0002436	94.46	gold quality
frontal cortex	UBERON:0001870	94.44	gold quality
prefrontal cortex	UBERON:0000451	94.33	gold quality
right frontal lobe	UBERON:0002810	93.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.46	gold quality
neocortex	UBERON:0001950	93.45	gold quality
blood	UBERON:0000178	93.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.36	gold quality
cerebral cortex	UBERON:0000956	93.30	gold quality
temporal lobe	UBERON:0001871	93.22	gold quality
Ammon’s horn	UBERON:0001954	93.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.94	gold quality
telencephalon	UBERON:0001893	92.80	gold quality
cingulate cortex	UBERON:0003027	92.44	gold quality
anterior cingulate cortex	UBERON:0009835	92.40	gold quality
nucleus accumbens	UBERON:0001882	92.32	gold quality
granulocyte	CL:0000094	92.24	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.76
E-MTAB-6075	no	499.44
E-MTAB-6386	no	432.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting MAST3, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 4)

• A single-nucleotide polymorphism (SNP)located in the second intron of the MAST3 gene is found to be associated in the screening and replication inflammatory bowel disease cohorts. (PMID:18650832)
• Together, the results suggest a complex antagonistic interplay between the control of ARPP-16 by MAST3 and PKA that creates a mechanism whereby cAMP mediates PP2A disinhibition. (PMID:28613156)
• Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy. (PMID:34185323)
• MiR-125a-3p inhibits cell proliferation and inflammation responses in fibroblast-like synovial cells in rheumatoid arthritis by mediating the Wnt/beta-catenin and NF-kappaB pathways via targeting MAST3. (PMID:34854396)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	mast3a	ENSDARG00000061725
danio_rerio	mast3b	ENSDARG00000086505
mus_musculus	Mast3	ENSMUSG00000031833
rattus_norvegicus	Mast3	ENSRNOG00000022753
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), SGK2 (ENSG00000101049), SGK3 (ENSG00000104205), DMPK (ENSG00000104936), MAST1 (ENSG00000105613), SGK1 (ENSG00000118515), MASTL (ENSG00000120539), LATS1 (ENSG00000131023), LATS2 (ENSG00000150457), STK32B (ENSG00000152953), STK32C (ENSG00000165752), STK32A (ENSG00000169302)

Protein

Protein identifiers

Microtubule-associated serine/threonine-protein kinase 3 — O60307 (reviewed: O60307)

All UniProt accessions (7): O60307, A0A8I5KST9, A0A8V8TLL8, A0A8V8TMM3, A0A8V8TMW0, A0A994J700, V9GYV0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with PTEN.

Subcellular location. Cytoplasm.

Disease relevance. Developmental and epileptic encephalopathy 108 (DEE108) [MIM:620115] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE108 is an autosomal dominant form characterized by the onset of multiple types of seizures in the first 2 years of life. 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 (22): NP_001380430, NP_001380431, NP_001380432, NP_001380433, NP_001380434, NP_001380435, NP_001380436, NP_001380437, NP_001380438, NP_001380439, NP_001380440, NP_001380441, NP_001380442, NP_001380443, NP_001380444, NP_001380445, NP_001380446, NP_001380447, NP_001380448, NP_001380449, NP_001380450, NP_055831 (=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 (59 total): modified residue 13, sequence variant 11, compositionally biased region 9, region of interest 7, helix 6, strand 5, domain 3, binding site 2, chain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3KHF	X-RAY DIFFRACTION	1.2
1V9V	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60307-F1	58.00	0.22

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): 490 (proton acceptor)

Ligand- & substrate-binding residues (2): 373–381; 396

Post-translational modifications (13): 66, 85, 146, 680, 710, 728, 754, 774, 782, 792, 793, 1223, 1273

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): MODULE_45, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, chr19p13, GOMF_MAGNESIUM_ION_BINDING, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, KIM_ALL_DISORDERS_OLIGODENDROCYTE_NUMBER_CORR_UP, KIM_ALL_DISORDERS_CALB1_CORR_UP, KIM_ALL_DISORDERS_DURATION_CORR_DN, BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING, ESC_V6.5_UP_EARLY.V1_UP

GO Biological Process (3): cytoskeleton organization (GO:0007010), intracellular signal transduction (GO:0035556), protein phosphorylation (GO:0006468)

GO Molecular Function (9): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), 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)

GO Cellular Component (2): cytoplasm (GO:0005737), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
organelle organization	1
signal transduction	1
phosphorylation	1
protein modification process	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
cellular anatomical structure	1
cytoskeleton	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAST3	MAGI3	Q5TCQ9	763
MAST3	SNTB2	Q13425	640
MAST3	ARPP19	P56211	604
MAST3	PTEN	P60484	562
MAST3	FRMD1	Q8N878	475
MAST3	ENSA	O43768	451
MAST3	DLG1	Q12959	417
MAST3	NEK2	P51955	407
MAST3	ABTB1	Q969K4	391
MAST3	CACNG2	Q9Y698	386
MAST3	WDR88	Q6ZMY6	383
MAST3	PPP2R5D	Q14738	380
MAST3	MAGI2	Q86UL8	373
MAST3	PDGFA	P04085	364
MAST3	S1PR2	O95136	355

IntAct

114 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
PTEN	MAST3	psi-mi:“MI:0915”(physical association)	0.700
MAST3	PTEN	psi-mi:“MI:0915”(physical association)	0.700
PTEN	MAST3	psi-mi:“MI:0217”(phosphorylation reaction)	0.700
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
PRKAB2	PRKAB2	psi-mi:“MI:0914”(association)	0.550
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PSG3	MGRN1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SLC15A5	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC4	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
E6	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
KIR3DL3	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
MAP2K2	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440
PBK	MAST3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (130): MAST3 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), C14orf166 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), CALU (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), YBX3 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), DDX21 (Affinity Capture-MS), DDX5 (Affinity Capture-MS), DRG1 (Affinity Capture-MS), EIF2A (Affinity Capture-MS), EIF2S1 (Affinity Capture-MS), EIF2S2 (Affinity Capture-MS), HNRNPM (Affinity Capture-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

2 interactions.

A	Effect	B	Mechanism
MAST3	up-regulates	PTEN	binding
MAST3	unknown	PTEN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	53.0×	4e-07
Activation of BAD and translocation to mitochondria	5	50.1×	2e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	44.2×	3e-06
Activation of BH3-only proteins	5	32.7×	1e-05
RHO GTPases activate PKNs	6	25.0×	5e-06
Intrinsic Pathway for Apoptosis	5	19.3×	1e-04
Oncogenic MAPK signaling	5	16.3×	3e-04
TP53 Regulates Metabolic Genes	9	15.4×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	17.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	193
Likely benign	50
Benign	7

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1723192	NM_001393504.1(MAST3):c.1630G>A (p.Gly544Ser)	Pathogenic
1723193	NM_001393504.1(MAST3):c.1634T>C (p.Leu545Pro)	Pathogenic
1723194	NM_001393504.1(MAST3):c.1738G>T (p.Val580Leu)	Pathogenic
1723195	NM_001393504.1(MAST3):c.1304G>C (p.Arg435Pro)	Pathogenic
2539695	NM_001393504.1(MAST3):c.1738G>C (p.Val580Leu)	Likely pathogenic
3370513	NM_001393504.1(MAST3):c.3895G>T (p.Asp1299Tyr)	Likely pathogenic
3543532	NM_001393504.1(MAST3):c.1556A>G (p.Asp519Gly)	Likely pathogenic

SpliceAI

4427 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18097827:TCCAG:T	donor_loss	1.0000
19:18097828:CCAG:C	donor_loss	1.0000
19:18097829:CAGGT:C	donor_loss	1.0000
19:18097830:AGG:A	donor_loss	1.0000
19:18097831:GGTGA:G	donor_loss	1.0000
19:18097832:G:GA	donor_loss	1.0000
19:18097833:T:A	donor_loss	1.0000
19:18107585:A:AG	acceptor_gain	1.0000
19:18107586:G:GG	acceptor_gain	1.0000
19:18121680:CACA:C	acceptor_loss	1.0000
19:18121681:ACAGC:A	acceptor_loss	1.0000
19:18121683:A:AG	acceptor_gain	1.0000
19:18121683:AG:A	acceptor_loss	1.0000
19:18121684:G:GA	acceptor_gain	1.0000
19:18121684:GC:G	acceptor_gain	1.0000
19:18121684:GCT:G	acceptor_gain	1.0000
19:18121772:GG:G	donor_gain	1.0000
19:18121773:GG:G	donor_gain	1.0000
19:18121922:GGTG:G	donor_loss	1.0000
19:18121923:GTGA:G	donor_loss	1.0000
19:18121924:T:G	donor_loss	1.0000
19:18122042:T:TA	acceptor_gain	1.0000
19:18122043:G:A	acceptor_gain	1.0000
19:18123203:C:G	acceptor_gain	1.0000
19:18123205:A:AG	acceptor_gain	1.0000
19:18123213:CCAGT:C	acceptor_loss	1.0000
19:18123214:CAG:C	acceptor_loss	1.0000
19:18123215:A:AG	acceptor_gain	1.0000
19:18123216:G:GC	acceptor_gain	1.0000
19:18123216:GT:G	acceptor_gain	1.0000

AlphaMissense

8694 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18128915:T:C	F367S	1.000
19:18128950:G:T	G379W	1.000
19:18130538:C:A	A394D	1.000
19:18130545:G:C	K396N	1.000
19:18130545:G:T	K396N	1.000
19:18134581:T:C	L496P	1.000
19:18134617:A:T	D508V	1.000
19:18145162:T:C	F962S	1.000
19:18145225:T:A	V983D	1.000
19:18145795:T:C	L1002P	1.000
19:18122689:T:A	W84R	0.999
19:18122689:T:C	W84R	0.999
19:18123964:T:C	L191P	0.999
19:18124029:T:C	F213L	0.999
19:18124030:T:C	F213S	0.999
19:18124031:C:A	F213L	0.999
19:18124031:C:G	F213L	0.999
19:18128914:T:C	F367L	0.999
19:18128915:T:G	F367C	0.999
19:18128916:T:A	F367L	0.999
19:18128916:T:G	F367L	0.999
19:18128933:T:A	I373N	0.999
19:18128935:A:C	S374R	0.999
19:18128936:G:T	S374I	0.999
19:18128937:C:A	S374R	0.999
19:18128937:C:G	S374R	0.999
19:18128950:G:A	G379R	0.999
19:18128950:G:C	G379R	0.999
19:18128951:G:A	G379E	0.999
19:18130499:T:A	V381D	0.999

dbSNP variants (sampled 300 via entrez): RS1000005947 (19:18145477 A>G), RS1000093999 (19:18096425 C>A,T), RS1000108044 (19:18097237 G>A), RS1000191428 (19:18122404 A>G), RS1000204935 (19:18120325 A>C), RS1000225163 (19:18128594 C>T), RS1000226926 (19:18114048 C>T), RS1000242367 (19:18122643 C>T), RS1000257468 (19:18120681 A>C,G), RS1000341555 (19:18103349 C>G,T), RS1000428081 (19:18125480 G>A), RS1000452762 (19:18137998 A>G), RS1000455059 (19:18142500 T>C), RS1000541655 (19:18102475 G>A), RS1000576267 (19:18121609 T>A,C,G)

Disease associations

OMIM: gene MIM:612258 | disease phenotypes: MIM:620115

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy 108	Strong	Autosomal dominant

Mondo (4): pervasive developmental disorder (MONDO:0000594), developmental and epileptic encephalopathy 108 (MONDO:0859314), developmental and epileptic encephalopathy (MONDO:0100620), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Rare pervasive developmental disorder (Orphanet:168778)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001249	Intellectual disability
HP:0002121	Generalized non-motor (absence) seizure
HP:0002384	Focal impaired awareness seizure
HP:0003593	Infantile onset
HP:0007334	Bilateral tonic-clonic seizure with focal onset
HP:0010819	Atonic seizure
HP:0011463	Childhood onset
HP:0012506	Small pituitary gland
HP:0025190	Bilateral tonic-clonic seizure with generalized onset
HP:0032660	Convulsive status epilepticus
HP:0032663	Focal motor status epilepticus
HP:0032792	Tonic seizure
HP:0032794	Myoclonic seizure
HP:0033725	Thin corpus callosum
HP:0200134	Epileptic encephalopathy

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST007326_58	Number of sexual partners	4.000000e-09
GCST007638_2	Glycine levels	4.000000e-09
GCST008157_70	Body fat mass	5.000000e-06
GCST008550_9	Mental health study participation (completed survey)	2.000000e-08
GCST008972_235	Urate levels	4.000000e-09
GCST010988_16	Adult body size	3.000000e-13
GCST011122_13	Walking pace	7.000000e-14
GCST012228_598	Waist-hip index	1.000000e-08
GCST012230_152	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90002382_458	Eosinophil percentage of white cells	2.000000e-09
GCST90002404_570	Red cell distribution width	4.000000e-21
GCST90011898_89	Alanine aminotransferase levels	9.000000e-23
GCST90013405_6	Liver enzyme levels (alanine transaminase)	4.000000e-28
GCST90016673_9	Percent liver fat	2.000000e-08
GCST90020024_531	A body shape index	2.000000e-09
GCST90020025_1421	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90020025_1422	Waist-to-hip ratio adjusted for BMI	7.000000e-11
GCST90020027_133	Waist-hip index	1.000000e-08
GCST90020027_134	Waist-hip index	6.000000e-11
GCST90020029_18	Waist circumference adjusted for body mass index	5.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0009767	glycine measurement
EFO:0010130	health study participation
EFO:0004531	urate measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007991	eosinophil percentage of leukocytes
EFO:0009188	Red cell distribution width
EFO:0010821	liver fat measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002659	Child Development Disorders, Pervasive	F03.625.164
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2417352 (SINGLE PROTEIN)

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

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs56022120	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs150688309	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs58695150	MAST3, PIK3R2	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs138602176	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs148235907	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs117951771	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs117341846	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs79430272	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs118129530	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs145623321	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs148013902	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs55633228	MAST3	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MAST family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 35 [PMID: 23916259]	Inhibition	6.62	pIC50

ChEMBL bioactivities

9 potent at pChembl≥5 of 9 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.62	IC50	240	nM	CHEMBL2420572
6.54	IC50	290	nM	CHEMBL2420564
6.13	IC50	740	nM	CHEMBL2420555
6.00	IC50	1010	nM	CHEMBL2420556
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.85	IC50	1400	nM	CHEMBL2420562
5.62	IC50	2400	nM	CHEMBL2420565

PubChem BioAssay actives

6 with measured affinity, of 56 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[(4-hydroxycyclohexyl)amino]-N-(1-phenylcyclopropyl)imidazo[1,2-a]quinoxaline-8-carboxamide	766863: Inhibition of MAST3 in human HuH7 cell lysates	ic50	0.2400	uM
4-[(4-hydroxycyclohexyl)amino]-N-[(1S)-2-hydroxy-1-phenylethyl]imidazo[1,2-a]quinoxaline-8-carboxamide	766863: Inhibition of MAST3 in human HuH7 cell lysates	ic50	0.2900	uM
N-[1-(4-fluorophenyl)cyclopropyl]-4-[(4-hydroxycyclohexyl)amino]imidazo[1,2-a]quinoxaline-8-carboxamide	766863: Inhibition of MAST3 in human HuH7 cell lysates	ic50	0.7400	uM
4-[(4-hydroxycyclohexyl)amino]-N-[(1R)-1-phenylethyl]imidazo[1,2-a]quinoxaline-8-carboxamide	766863: Inhibition of MAST3 in human HuH7 cell lysates	ic50	1.0100	uM
4-[(4-hydroxycyclohexyl)amino]-N-[(1R)-1-phenylpropyl]imidazo[1,2-a]quinoxaline-8-carboxamide	766863: Inhibition of MAST3 in human HuH7 cell lysates	ic50	1.4000	uM
4-[(4-hydroxycyclohexyl)amino]-N-[(1R)-1-phenylbutyl]imidazo[1,2-a]quinoxaline-8-carboxamide	766863: Inhibition of MAST3 in human HuH7 cell lysates	ic50	2.4000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

38 unique, capped per target: 38 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2424216	Binding	Inhibition of MAST3 in human HuH7 cell lysates	Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SX22	HAP1 MAST3 (-) 1	Cancer cell line	Male
CVCL_SX23	HAP1 MAST3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205699	PHASE4	COMPLETED	Metabolic Effects of Antipsychotics in Children
NCT01238575	PHASE4	COMPLETED	Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
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,
NCT00399698	PHASE3	COMPLETED	Study to Determine Whether There Are Any Cognitive or Motor Effects From Taking the Medicine Risperidone.
NCT00870727	PHASE3	COMPLETED	Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
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
NCT00198055	PHASE2	COMPLETED	A Study of Aripiprazole in Children and Adolescents With Aspergers and Pervasive Developmental Disorder.
NCT00308074	PHASE2	COMPLETED	An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders
NCT01602016	PHASE2	TERMINATED	A Folinic Acid Intervention for Autism Spectrum Disorders
NCT05664841	PHASE2	RECRUITING	The Impact of a Virtual Magic Trick Training Program
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
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
NCT00325572	PHASE1	TERMINATED	Evaluation and Treatment of Copper/Zinc Imbalance in Children With Autism
NCT00773812	PHASE1	COMPLETED	Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
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
NCT01243905	PHASE2/PHASE3	UNKNOWN	Group Psychoeducational Program for Mothers of Children With High Functional Pervasive Developmental Disorders
NCT00318162	PHASE1/PHASE2	UNKNOWN	Trial of Low-Dose Naltrexone for Children With Pervasive Developmental Disorder (PDD)
NCT00004458	Not specified	TERMINATED	Longitudinal and Biological Study of Childhood Disintegrative Disorder
NCT00025779	Not specified	COMPLETED	Methylphenidate in Children and Adolescents With Pervasive Developmental Disorders
NCT00464477	Not specified	COMPLETED	Advanced Grandparental Age as a Risk Factor for Autism
NCT00531830	Not specified	UNKNOWN	Assessment of Factors Which Predict Improvement in Children With PDD After a Year of Integrative Therapy
NCT00579267	Not specified	COMPLETED	Reliability and Validity of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)
NCT00902798	Not specified	COMPLETED	Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder