MAST4

Summary

MAST4 (microtubule associated serine/threonine kinase family member 4, HGNC:19037) is a protein-coding gene on chromosome 5q12.3, encoding Microtubule-associated serine/threonine-protein kinase 4 (O15021).

This gene encodes a member of the microtubule-associated serine/threonine protein kinases. The proteins in this family contain a domain that gives the kinase the ability to determine its own scaffold to control the effects of their kinase activities. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 375449 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 31
• Clinical variants (ClinVar): 403 total — 3 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001164664

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19037
Approved symbol	MAST4
Name	microtubule associated serine/threonine kinase family member 4
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0303
Ensembl gene	ENSG00000069020
Ensembl biotype	protein_coding
OMIM	618002
Entrez	375449

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000261569, ENST00000403625, ENST00000403666, ENST00000405643, ENST00000406039, ENST00000406374, ENST00000407621, ENST00000411628, ENST00000432426, ENST00000432817, ENST00000434115, ENST00000436277, ENST00000443808, ENST00000447738, ENST00000450827, ENST00000451144, ENST00000452953, ENST00000470421, ENST00000478569, ENST00000485768, ENST00000490016

RefSeq mRNA: 12 — MANE Select: NM_001164664 NM_001164664, NM_001290226, NM_001290227, NM_001290228, NM_001297651, NM_001393524, NM_001393525, NM_001393526, NM_001393527, NM_001393528, NM_015183, NM_198828

CCDS: CCDS47224, CCDS47225, CCDS54861, CCDS75254, CCDS78015

Canonical transcript exons

ENST00000403625 — 29 exons

Exon	Start	End
ENSE00000429432	67130210	67130418
ENSE00000429434	67133514	67133646
ENSE00000429448	67142421	67142533
ENSE00000750490	67145144	67145379
ENSE00000750494	67142115	67142237
ENSE00000750499	67121017	67121102
ENSE00000750507	67118682	67118749
ENSE00000837136	67136563	67136664
ENSE00000971546	67100435	67100592
ENSE00000971549	67110098	67110199
ENSE00000971560	67144669	67144796
ENSE00001082494	67114087	67114219
ENSE00001147323	67102536	67102611
ENSE00001147331	67095597	67095675
ENSE00001147347	67054404	67054492
ENSE00001420586	66788670	66788794
ENSE00001538222	67131813	67131951
ENSE00001548908	66596393	66597018
ENSE00001550981	67163147	67169593
ENSE00001610267	67152637	67152866
ENSE00001631644	67162607	67162788
ENSE00001726877	67153458	67153580
ENSE00001767617	67090162	67090231
ENSE00001788647	67134523	67134688
ENSE00002154523	67149389	67149589
ENSE00002724527	67160456	67160592
ENSE00003468553	66759709	66759862
ENSE00003491472	67104366	67104575
ENSE00003614435	66899951	66899982

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4615 / max 601.9679, expressed in 1639 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56768	7.1651	1329
56737	4.5261	675
56752	4.2917	760
56769	1.3095	657
56767	1.0577	572
56761	0.8424	219
56771	0.7440	256
56765	0.5918	307
56766	0.5059	247
56770	0.2868	131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	99.53	gold quality
cartilage tissue	UBERON:0002418	97.93	gold quality
squamous epithelium	UBERON:0006914	97.93	gold quality
nipple	UBERON:0002030	97.88	gold quality
oocyte	CL:0000023	97.85	gold quality
secondary oocyte	CL:0000655	97.80	gold quality
gingival epithelium	UBERON:0001949	97.61	gold quality
cervix epithelium	UBERON:0004801	97.51	gold quality
esophagus squamous epithelium	UBERON:0006920	97.51	gold quality
buccal mucosa cell	CL:0002336	97.35	gold quality
pharyngeal mucosa	UBERON:0000355	97.24	gold quality
tongue squamous epithelium	UBERON:0006919	97.11	gold quality
oviduct epithelium	UBERON:0004804	97.07	gold quality
gingiva	UBERON:0001828	96.86	gold quality
epithelium of esophagus	UBERON:0001976	96.58	gold quality
mucosa of urinary bladder	UBERON:0001259	96.22	gold quality
mammalian vulva	UBERON:0000997	96.14	gold quality
sperm	CL:0000019	96.13	gold quality
penis	UBERON:0000989	96.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.93	gold quality
renal medulla	UBERON:0000362	95.88	gold quality
left ventricle myocardium	UBERON:0006566	95.34	gold quality
middle temporal gyrus	UBERON:0002771	95.22	gold quality
visceral pleura	UBERON:0002401	95.16	gold quality
male germ cell	CL:0000015	94.97	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.76	gold quality
oral cavity	UBERON:0000167	94.70	gold quality
apex of heart	UBERON:0002098	94.66	gold quality
heart right ventricle	UBERON:0002080	94.35	gold quality
hair follicle	UBERON:0002073	94.30	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	39.43
E-MTAB-8271	yes	15.10
E-HCAD-29	no	316.74
E-MTAB-8205	no	173.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

161 targeting MAST4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 7)

• high expression level of MAST4 in most normal human tissues, with an exception of in testis, small intestine, colon and peripheral blood leukocyte. (PMID:17086981)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Molecular studies incriminated different genes, mainly CACNA1H and MAST4. Since at least 2 susceptibility genes were likely shared by different populations, genetic factors involved in the majority of Tunisian Genetic generalized epilepsies families remain to be discovered. (PMID:29948376)
• Mast4 knockout shows the regulation of spermatogonial stem cell self-renewal via the FGF2/ERM pathway. (PMID:33219327)
• Estrogen-Responsive Gene MAST4 Regulates Myeloma Bone Disease. (PMID:35064934)
• Nuclear MAST4 Suppresses FOXO3 through Interaction with AKT3 and Induces Chemoresistance in Pancreatic Ductal Carcinoma. (PMID:38612866)
• MAST4 regulates stem cell maintenance with DLX3 for epithelial development and amelogenesis. (PMID:38945953)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mast4	ENSMUSG00000034751
rattus_norvegicus	Mast4	ENSRNOG00000027002
drosophila_melanogaster	CG32944	FBGN0052944
drosophila_melanogaster	dop	FBGN0267390
caenorhabditis_elegans		WBGENE00002192
caenorhabditis_elegans	wts-1	WBGENE00007047
caenorhabditis_elegans		WBGENE00010838
caenorhabditis_elegans		WBGENE00011992

Paralogs (13): MAST2 (ENSG00000086015), MAST3 (ENSG00000099308), 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 4 — O15021 (reviewed: O15021)

All UniProt accessions (13): O15021, B5MC73, C9J249, C9JKM7, D6RAK1, E7EX28, F8WBH1, H7C0U3, H7C146, H7C1I9, H7C2A9, H7C2V7, H7C3S4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in most normal human tissues, with an exception of in testis, small intestine, colon and peripheral blood leukocyte.

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

Isoforms (5)

UniProt ID	Names	Canonical?
O15021-5	1	yes
O15021-2	2
O15021-4	4
O15021-3	3
O15021-6	5

RefSeq proteins (12): NP_001158136, NP_001277155, NP_001277156, NP_001277157, NP_001284580, NP_001380453, NP_001380454, NP_001380455, NP_001380456, NP_001380457, NP_055998, NP_942123 (=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 (98 total): compositionally biased region 33, modified residue 17, region of interest 16, splice variant 6, sequence variant 6, sequence conflict 5, strand 5, domain 3, binding site 2, helix 2, chain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2W7R	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15021-F1	43.32	0.12

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): 693 (proton acceptor)

Ligand- & substrate-binding residues (2): 576–584; 599

Post-translational modifications (17): 206, 213, 270, 914, 1292, 1370, 1384, 1397, 1419, 1467, 1523, 1779, 1822, 1909, 2442, 2520, 2552

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 268 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, BENPORATH_ES_WITH_H3K27ME3, JAEGER_METASTASIS_DN, GOZGIT_ESR1_TARGETS_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, DING_LUNG_CANCER_BY_MUTATION_RATE, BILD_HRAS_ONCOGENIC_SIGNATURE, CAIRO_HEPATOBLASTOMA_CLASSES_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, ENGELMANN_CANCER_PROGENITORS_UP, AACTTT_UNKNOWN, FREAC4_01, ZHAN_MULTIPLE_MYELOMA_LB_UP

GO Biological Process (4): cytoskeleton organization (GO:0007010), developmental process (GO:0032502), intracellular signal transduction (GO:0035556), protein phosphorylation (GO:0006468)

GO Molecular Function (10): 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), metal ion binding (GO:0046872)

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
biological_process	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
cation binding	1
cellular anatomical structure	1
cytoskeleton	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAST4	SNTB2	Q13425	557
MAST4	NDUFAF2	Q8N183	508
MAST4	ZNF573	Q86YE8	476
MAST4	MCTP2	Q6DN12	426
MAST4	PTGS1	P23219	426
MAST4	PRDM15	P57071	423
MAST4	UNC80	Q8N2C7	423
MAST4	CMC2	Q9NRP2	418
MAST4	TP53I11	O14683	418
MAST4	ASTN2	O75129	414
MAST4	SLC14A2	Q15849	413
MAST4	A0A087WVV2	A0A087WVV2	412
MAST4	COL19A1	Q14993	410
MAST4	GDAP1	Q8TB36	409
MAST4	NEK2	P51955	408
MAST4	PKHD1L1	Q86WI1	408

IntAct

43 interactions, top by confidence:

A	B	Type	Score
MAST4	ABCC4	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
MAST4	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
MAST4	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
E6	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
MAST4	ORF putative E6	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
KIR3DL3	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
MAP2K2	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
PBK	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
RALBP1	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
RASSF6	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
SLCO1C1	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
TJP2	MAST4	psi-mi:“MI:0407”(direct interaction)	0.440
MAST4	BICD2	psi-mi:“MI:0915”(physical association)	0.400
MAST4	SMAD1	psi-mi:“MI:0915”(physical association)	0.370
STK38L		psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
CILK1	MAST4	psi-mi:“MI:0914”(association)	0.350
MAST1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): MAST4 (Proximity Label-MS), BICD2 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Proximity Label-MS), MAST4 (Affinity Capture-MS), MAST4 (Affinity Capture-MS), OLA1 (Co-fractionation)

ESM2 similar proteins: A0A1W2PPD8, A2A3K4, A4Q9E5, A4Q9F0, A4Q9F1, A6PVC2, A7E379, B2GUB3, D3YWQ0, F1MAB7, O00295, O15021, O75912, O89084, O94953, O94966, P03177, P15304, P46686, P54748, Q08493, Q0P4M4, Q14999, Q1ECV4, Q1HVD1, Q28969, Q3KSQ2, Q3ULB5, Q4G017, Q5R8Z4, Q5R978, Q5RCJ3, Q5TKR9, Q6EEF3, Q6EMB2, Q6J1Y9, Q6NZK8, Q6X4W1, Q6ZT98, Q7TNN8

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
MAST4	“down-regulates activity”	FOXO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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
Activation of BAD and translocation to mitochondria	5	115.3×	6e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	101.8×	6e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	101.8×	6e-08
Activation of BH3-only proteins	5	75.2×	3e-07
RHO GTPases activate PKNs	5	48.1×	2e-06
Intrinsic Pathway for Apoptosis	5	44.4×	3e-06
SARS-CoV-1-host interactions	5	26.6×	3e-05
Apoptosis	5	25.4×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	323
Likely benign	38
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1809802	NM_001164664.2(MAST4):c.2693T>C (p.Ile898Thr)	Likely pathogenic
1809804	NM_001164664.2(MAST4):c.7655C>G (p.Ser2552Trp)	Likely pathogenic
982228	NM_001164664.2(MAST4):c.3475C>T (p.Arg1159Trp)	Likely pathogenic

SpliceAI

3880 predictions. Top by Δscore:

Variant	Effect	Δscore
5:66899949:A:AG	acceptor_gain	1.0000
5:66899950:G:GA	acceptor_gain	1.0000
5:66899950:GAA:G	acceptor_gain	1.0000
5:66899976:G:GT	donor_gain	1.0000
5:66899979:GTTT:G	donor_gain	1.0000
5:66899983:G:GG	donor_gain	1.0000
5:67054398:T:A	acceptor_gain	1.0000
5:67054400:ATAG:A	acceptor_loss	1.0000
5:67054401:TAGT:T	acceptor_loss	1.0000
5:67054402:A:AG	acceptor_gain	1.0000
5:67054402:AGT:A	acceptor_loss	1.0000
5:67054402:AGTT:A	acceptor_gain	1.0000
5:67054403:G:GA	acceptor_gain	1.0000
5:67054403:GT:G	acceptor_gain	1.0000
5:67054403:GTT:G	acceptor_gain	1.0000
5:67054403:GTTG:G	acceptor_gain	1.0000
5:67054403:GTTGC:G	acceptor_gain	1.0000
5:67054490:CAGG:C	donor_loss	1.0000
5:67054491:AGGTA:A	donor_loss	1.0000
5:67054492:GG:G	donor_loss	1.0000
5:67054493:G:GC	donor_loss	1.0000
5:67054494:T:A	donor_loss	1.0000
5:67104360:A:AG	acceptor_gain	1.0000
5:67104361:T:G	acceptor_gain	1.0000
5:67104362:A:AG	acceptor_gain	1.0000
5:67104362:ATAG:A	acceptor_gain	1.0000
5:67104363:T:G	acceptor_gain	1.0000
5:67104364:A:AG	acceptor_gain	1.0000
5:67104364:AG:A	acceptor_gain	1.0000
5:67104365:G:GT	acceptor_gain	1.0000

AlphaMissense

17075 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:67095613:T:A	W284R	1.000
5:67095613:T:C	W284R	1.000
5:67095615:G:C	W284C	1.000
5:67095615:G:T	W284C	1.000
5:67100469:T:C	L316S	1.000
5:67100505:T:C	L328S	1.000
5:67102584:C:A	N373K	1.000
5:67102584:C:G	N373K	1.000
5:67102603:T:C	F380L	1.000
5:67102604:T:C	F380S	1.000
5:67102605:C:A	F380L	1.000
5:67102605:C:G	F380L	1.000
5:67104456:T:C	F413L	1.000
5:67104458:C:A	F413L	1.000
5:67104458:C:G	F413L	1.000
5:67110186:T:C	L482S	1.000
5:67110194:T:C	C485R	1.000
5:67110198:T:C	L486P	1.000
5:67114090:T:C	F488L	1.000
5:67114092:T:A	F488L	1.000
5:67114092:T:G	F488L	1.000
5:67114105:T:C	F493L	1.000
5:67114106:T:C	F493S	1.000
5:67114106:T:G	F493C	1.000
5:67114107:T:A	F493L	1.000
5:67114107:T:G	F493L	1.000
5:67114115:T:C	L496P	1.000
5:67114118:T:C	L497S	1.000
5:67114123:G:C	A499P	1.000
5:67114126:G:C	A500P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002595 (5:67130792 C>G), RS1000013841 (5:66621896 G>A,T), RS1000020850 (5:67027452 A>G), RS1000025778 (5:67094143 C>T), RS1000037218 (5:66887147 G>A), RS1000049397 (5:67086347 C>G), RS1000054357 (5:66967291 G>A), RS1000080004 (5:66640152 A>G), RS1000080269 (5:66921090 A>G), RS1000086682 (5:66762991 T>C), RS1000090626 (5:66663207 G>A,T), RS1000093838 (5:66871474 A>G), RS1000099481 (5:66720407 T>C), RS1000105867 (5:66946505 G>A), RS1000114165 (5:66907322 A>G)

Disease associations

OMIM: gene MIM:618002 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000555_5	Carotid atherosclerosis in HIV infection	2.000000e-06
GCST001662_10	Generalized epilepsy	3.000000e-07
GCST003262_617	Post bronchodilator FEV1	4.000000e-06
GCST003264_869	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003814_15	Selective IgA deficiency	2.000000e-06
GCST004599_99	Mean platelet volume	7.000000e-10
GCST004603_227	Platelet count	1.000000e-12
GCST005194_246	Coronary artery disease	2.000000e-06
GCST005196_84	Coronary artery disease	2.000000e-07
GCST005655_1	Seborrheic dermatitis	2.000000e-08
GCST006630_68	Diastolic blood pressure	9.000000e-14
GCST006870_3	Hippocampal tail volume	1.000000e-10
GCST006871_2	Total hippocampal volume	9.000000e-11
GCST007267_16	Systolic blood pressure	3.000000e-12
GCST008462_2	Plasma factor V levels in venous thrombosis (conditioned on rs6027)	5.000000e-06
GCST009524_81	Household income (MTAG)	2.000000e-08
GCST010172_16	Idiopathic downbeat nystagmus	7.000000e-06
GCST010701_109	Cortical surface area (MOSTest)	4.000000e-12
GCST010702_159	Subcortical volume (MOSTest)	4.000000e-22
GCST010703_196	Brain morphology (MOSTest)	1.000000e-10
GCST010796_3122	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010988_92	Adult body size	5.000000e-11
GCST010989_250	Body size at age 10	8.000000e-14
GCST011617_14	Cortical surface area	4.000000e-14
GCST011940_1	Bullous pemphigoid	4.000000e-38
GCST012490_594	Femur bone mineral density x serum urate levels interaction	2.000000e-10
GCST90002395_669	Mean platelet volume	6.000000e-24
GCST90002400_684	Plateletcrit	1.000000e-12
GCST90002402_764	Platelet count	9.000000e-16
GCST90002402_765	Platelet count	6.000000e-09

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004309	platelet count
EFO:0006336	diastolic blood pressure
EFO:0005035	hippocampal volume
EFO:0006335	systolic blood pressure
EFO:0009695	household income
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004531	urate measurement
EFO:0007985	platelet crit
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2417351 (SINGLE PROTEIN)

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

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression	7
bisphenol A	affects methylation, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
bisphenol S	affects cotreatment, decreases methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Dexamethasone	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects methylation	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
trametinib	decreases expression, affects cotreatment	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2424215	Binding	Inhibition of MAST4 in human HuH7 cell lysates at 10 uM	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

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SX24	HAP1 MAST4 (-) 1	Cancer cell line	Male
CVCL_SX25	HAP1 MAST4 (-) 2	Cancer cell line	Male
CVCL_SX26	HAP1 MAST4 (-) 3	Cancer cell line	Male
CVCL_SX27	HAP1 MAST4 (-) 4	Cancer cell line	Male
CVCL_SX28	HAP1 MAST4 (-) 5	Cancer cell line	Male
CVCL_SX29	HAP1 MAST4 (-) 6	Cancer cell line	Male

Clinical trials (associated diseases)

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

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