MRTFB

Summary

MRTFB (myocardin related transcription factor B, HGNC:29819) is a protein-coding gene on chromosome 16p13.12, encoding Myocardin-related transcription factor B (Q9ULH7). Acts as a transcriptional coactivator of serum response factor (SRF).

Enables transcription coactivator activity. Involved in positive regulation of miRNA transcription; positive regulation of striated muscle tissue development; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in several cellular components, including glutamatergic synapse; postsynapse; and presynapse.

Source: NCBI Gene 57496 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 36
• Clinical variants (ClinVar): 174 total — 3 pathogenic
• MANE Select transcript: NM_001308142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29819
Approved symbol	MRTFB
Name	myocardin related transcription factor B
Location	16p13.12
Locus type	gene with protein product
Status	Approved
Aliases	MRTF-B, FLJ31823
Ensembl gene	ENSG00000186260
Ensembl biotype	protein_coding
OMIM	609463
Entrez	57496

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000318282, ENST00000571589, ENST00000571770, ENST00000572400, ENST00000572567, ENST00000572588, ENST00000573051, ENST00000573434, ENST00000574045, ENST00000574998, ENST00000575537, ENST00000575768, ENST00000575833, ENST00000910537, ENST00000910538, ENST00000910539, ENST00000910540, ENST00000910541, ENST00000932862, ENST00000932863, ENST00000932864, ENST00000932866, ENST00000932867

RefSeq mRNA: 9 — MANE Select: NM_001308142 NM_001308142, NM_001365411, NM_001365412, NM_001365413, NM_001365414, NM_001365415, NM_001365416, NM_001365417, NM_014048

CCDS: CCDS32391, CCDS76823, CCDS92112

Canonical transcript exons

ENST00000571589 — 17 exons

Exon	Start	End
ENSE00000000145	14071319	14071365
ENSE00000668749	14248926	14249081
ENSE00001202958	14245528	14245660
ENSE00001218988	14240237	14240484
ENSE00001218994	14234146	14234283
ENSE00001385516	14246473	14247507
ENSE00001504921	14218820	14218998
ENSE00001780957	14217126	14217287
ENSE00002640057	14079290	14079354
ENSE00002657604	14260909	14266773
ENSE00003492330	14213545	14213620
ENSE00003506306	14212354	14212409
ENSE00003525727	14140544	14140760
ENSE00003581312	14252365	14252502
ENSE00003590130	14210243	14210308
ENSE00003596249	14251862	14252023
ENSE00003637253	14258101	14258161

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4275 / max 875.5705, expressed in 1383 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152854	2.8227	260
152849	2.8002	1236
152855	1.4939	221
152848	0.4351	232
152853	0.2966	65
152858	0.2872	82
152856	0.2710	111
152864	0.2526	109
152852	0.2208	55
152867	0.2001	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.25	gold quality
endothelial cell	CL:0000115	99.05	gold quality
middle temporal gyrus	UBERON:0002771	98.61	gold quality
CA1 field of hippocampus	UBERON:0003881	97.90	gold quality
entorhinal cortex	UBERON:0002728	97.62	gold quality
superior frontal gyrus	UBERON:0002661	97.52	gold quality
orbitofrontal cortex	UBERON:0004167	97.26	gold quality
postcentral gyrus	UBERON:0002581	97.18	gold quality
parietal lobe	UBERON:0001872	97.16	gold quality
visceral pleura	UBERON:0002401	96.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.82	gold quality
parietal pleura	UBERON:0002400	96.75	gold quality
pleura	UBERON:0000977	96.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.39	gold quality
skin of hip	UBERON:0001554	96.12	gold quality
upper leg skin	UBERON:0004262	95.21	gold quality
occipital lobe	UBERON:0002021	94.86	gold quality
urethra	UBERON:0000057	94.82	gold quality
lateral globus pallidus	UBERON:0002476	94.79	gold quality
synovial joint	UBERON:0002217	94.75	gold quality
primary visual cortex	UBERON:0002436	94.52	gold quality
hair follicle	UBERON:0002073	94.50	gold quality
choroid plexus epithelium	UBERON:0003911	94.45	gold quality
epithelium of bronchus	UBERON:0002031	94.43	gold quality
bronchus	UBERON:0002185	94.34	gold quality
penis	UBERON:0000989	94.19	gold quality
mammary gland	UBERON:0001911	94.02	gold quality
thoracic mammary gland	UBERON:0005200	93.97	gold quality
seminal vesicle	UBERON:0000998	93.96	gold quality
epithelium of mammary gland	UBERON:0003244	93.93	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	1197.81
E-HCAD-25	yes	89.58
E-HCAD-35	yes	88.41
E-ANND-3	yes	19.11
E-GEOD-99795	no	176.01
E-MTAB-10596	no	94.66
E-MTAB-6386	no	20.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

224 targeting MRTFB, 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-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-27A-3P	99.98	72.13	2955

Literature-anchored findings (GeneRIF, showing 21)

• dominant negative MKL2 blocked differentiation-induced expression of SRF target genes skeletal alpha-actin and alpha-myosin heavy chain and blocked differentiation of the myoblasts to myotubes in vitro. (PMID:14565952)
• BMP signaling modulates VSMC phenotype via cross-talk with the RhoA/MRTFs pathway, and may contribute to the development of the pathological characteristics observed in patients with PAH and other obliterative vascular diseases. (PMID:17947237)
• Myocardin-related transcription factors are critical mediators of transforming growth factor beta (TGF-beta) 1-induced epithelial-mesenchymal transition.[ (PMID:18056415)
• RNA interference was used to investigate the contribution of the MRTF-SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, in which basal MRTF-SRF activity is Rho-dependent. (PMID:19198601)
• C11orf95-MKL2 is the resulting fusion oncogene of t(11;16)(q13;p13) in chondroid lipoma. (PMID:20607705)
• study provides evidence that MKL1/2 mediates cancerous transformation in DLC1-deficient hepatocellular and mammary carcinoma cells (PMID:22139079)
• Based on a recurrent translocation t(11;16)(q13;p13), the C11orf95-MKL2 fusion gene has been found in eight further cases of chondroid lipomas. (PMID:23672313)
• While disruption of the MKL2:SRF axis has been associated with severe microcephaly and disordered brain development in multiple model systems, the role of this transcription factor complex has not been previously demonstrated in human brain development. (PMID:23692340)
• MKL1/2 depletion resulted in Ras activation, elevated p16 expression and hypophosphorylation of the retinoblastoma (Rb) protein in DLC1-deficient hepatocellular carcinoma cells. (PMID:23853104)
• There were multiple independent HIV integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. (PMID:24968937)
• Study showed that MRTF-A and MRTF-B were upregulated in pancreatic cancer tissues supporting the hypothesis that both of them are oncogenes in pancreatic cancer. (PMID:26498848)
• Our new data identifies and important contribution of MKL1/2 to explaining the strikingly different response of VSMCs and ECs to cAMP elevation. Elucidation of these pathways promises to identify targets for specific inhibition of VSMC migration and proliferation. (PMID:28623279)
• Taken together, these findings suggest that MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation. (PMID:29335431)
• Ectomesenchymal chondromyxoid tumors are characterized by an RREB1-MKL2 fusion gene. (PMID:29912715)
• These studies implicate the actin cytoskeleton and ELK3, FLI1, and MKL2 in the transcriptional control of EDNRB and increase our understanding of the plasticity of this receptor (PMID:30332284)
• Lower MRTFB expression levels are associated with shorter survival of patients with GI tract cancer. MRTFB targets SPDL1 and MCAM to inhibit CRC cell motility and tumor growth. Depletion of MRTFB in human CRC Cells increases cell motility and accelerates tumor growth in xenograft assays. (PMID:31690663)
• The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial-Mesenchymal Transition. (PMID:32824297)
• Oxidative Stress Enhances the TGF-beta2-RhoA-MRTF-A/B Axis in Cells Entering Endothelial-Mesenchymal Transition. (PMID:35216178)
• De novo variants in MRTFB have gain-of-function activity in Drosophila and are associated with a novel neurodevelopmental phenotype with dysmorphic features. (PMID:37013900)
• Role of CRP2-MRTF interaction in functions of myofibroblasts. (PMID:37164693)
• KLF15 maintains contractile phenotype of vascular smooth muscle cells and prevents thoracic aortic dissection by interacting with MRTFB. (PMID:38582447)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrtfbb	ENSDARG00000076867
danio_rerio	mrtfba	ENSDARG00000088307
mus_musculus	Mrtfb	ENSMUSG00000009569
rattus_norvegicus	Mrtfb	ENSRNOG00000066694
drosophila_melanogaster	Mrtf	FBGN0052296
caenorhabditis_elegans		WBGENE00004145

Paralogs (2): MYOCD (ENSG00000141052), MRTFA (ENSG00000196588)

Protein

Protein identifiers

Myocardin-related transcription factor B — Q9ULH7 (reviewed: Q9ULH7)

Alternative names: MKL/myocardin-like protein 2, Megakaryoblastic leukemia 2

All UniProt accessions (5): Q9ULH7, I3L0U1, I3L2A0, I3L2S3, I3L3Z7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional coactivator of serum response factor (SRF). Required for skeletal myogenic differentiation.

Subunit / interactions. Interacts with MRTFA and SRF.

Subcellular location. Nucleus.

Post-translational modifications. O-glycosylated.

Disease relevance. A chromosomal aberration involving ZFTA is found in 3 chondroid lipomas. Translocation t(11;16)(q13;p13) with ZFTA produces a ZFTA-MRTFB fusion protein.

Domain organisation. The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9ULH7-1	1	yes
Q9ULH7-2	2
Q9ULH7-3	3
Q9ULH7-4	4
Q9ULH7-5	5

RefSeq proteins (8): NP_001295071, NP_001352340, NP_001352341, NP_001352342, NP_001352343, NP_001352344, NP_001352345, NP_054767 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR004018	RPEL_repeat	Repeat
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR043451	Myocardin-like	Family

Pfam: PF02037, PF02755

UniProt features (46 total): compositionally biased region 10, modified residue 8, region of interest 7, splice variant 7, sequence conflict 5, repeat 3, chain 1, coiled-coil region 1, site 1, cross-link 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULH7-F1	53.38	0.18

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): 394 (breakpoint for translocation to form zfta-mrtfb fusion protein)

Post-translational modifications (9): 66, 367, 370, 541, 543, 921, 628, 22, 22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, TGCGCANK_UNKNOWN, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GCM_CALM1, GCM_MAPK10, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, SENESE_HDAC3_TARGETS_DN, GOCC_NUCLEAR_SPECK, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (7): muscle organ development (GO:0007517), positive regulation of striated muscle tissue development (GO:0045844), positive regulation of transcription by RNA polymerase II (GO:0045944), smooth muscle cell differentiation (GO:0051145), regulation of modification of postsynaptic structure (GO:0099159), positive regulation of miRNA transcription (GO:1902895), cell differentiation (GO:0030154)

GO Molecular Function (5): transcription coactivator activity (GO:0003713), cadherin binding (GO:0045296), actin binding (GO:0003779), protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	3
cellular anatomical structure	3
synapse	3
animal organ development	1
muscle structure development	1
striated muscle tissue development	1
regulation of striated muscle tissue development	1
positive regulation of muscle organ development	1
positive regulation of muscle tissue development	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
muscle cell differentiation	1
modification of postsynaptic structure	1
regulation of modification of synaptic structure	1
miRNA transcription	1
regulation of miRNA transcription	1
positive regulation of miRNA metabolic process	1
cellular developmental process	1
transcription coregulator activity	1
cell adhesion molecule binding	1
cytoskeletal protein binding	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRTFB	SRF	P11831	955
MRTFB	PHACTR1	Q9C0D0	944
MRTFB	RHOA	P06749	784
MRTFB	RBM15	Q96T37	749
MRTFB	ZFTA	C9JLR9	644
MRTFB	ABRA	Q8N0Z2	533
MRTFB	BACH2	Q9BYV9	529
MRTFB	MAMSTR	Q6ZN01	465
MRTFB	MDGA2	Q7Z553	426
MRTFB	SDHC	Q99643	420
MRTFB	KCNH8	Q96L42	416
MRTFB	FBXO33	Q7Z6M2	411
MRTFB	TAGLN	Q01995	406
MRTFB	GALNT13	Q8IUC8	406
MRTFB	HS3ST5	Q8IZT8	390

IntAct

44 interactions, top by confidence:

A	B	Type	Score
MRTFB	SRF	psi-mi:“MI:0915”(physical association)	0.660
SRF	MRTFB	psi-mi:“MI:0915”(physical association)	0.660
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
MRTFB	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
KPNA4	MRTFB	psi-mi:“MI:0915”(physical association)	0.400
MRTFB	MRTFB	psi-mi:“MI:0915”(physical association)	0.400
MRTFA	MRTFB	psi-mi:“MI:0915”(physical association)	0.400
SMAD7	MRTFB	psi-mi:“MI:0915”(physical association)	0.370
SMAD1	MRTFB	psi-mi:“MI:0915”(physical association)	0.370
MRTFB	SVIL	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
STK38L		psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPK1	SEC16A	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
ODF2	EIF3F	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
FHL3	COBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): MKL2 (Affinity Capture-MS), MKL2 (Reconstituted Complex), MKL2 (Affinity Capture-MS), MKL2 (Affinity Capture-MS), MKL2 (Proximity Label-MS), MKL2 (Affinity Capture-MS), MKL2 (Affinity Capture-MS), MKL2 (Affinity Capture-RNA), MKL2 (Affinity Capture-MS), SRF (Affinity Capture-Western), MKL2 (Affinity Capture-Western), MKL2 (Affinity Capture-Western), MKL2 (Proximity Label-MS), MKL2 (Proximity Label-MS), MKL2 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JN51, A0JP82, A2AWL7, A2BGM5, A2RRX6, F8VPJ6, K9JHZ4, O13186, O46567, O54826, O89091, P04150, P08235, P15822, P22199, P32519, P36197, P37275, P48552, P55197, P59759, P79269, P79686, Q29131, Q2KHR2, Q3YC04, Q4JM28, Q5R9P5, Q60775, Q61321, Q62947, Q64318, Q68DE3, Q6XLJ0, Q8AYC1, Q8AYC2, Q8BMA5, Q8IZQ8

Diamond homologs: P59759, Q8AYC1, Q8AYC2, Q8IZQ8, Q8K4J6, Q8R5I7, Q969V6, Q9ULH7, A7E346, Q0ZCJ7, Q6ZN01, Q7YR76, Q8VIM5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MRTFB	up-regulates	SRF	binding
MRTFB	“up-regulates activity”	SRF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
Recycling pathway of L1	5	28.7×	1e-04
MITF-M-regulated melanocyte development	6	17.6×	1e-04
RHO GTPase Effectors	7	12.2×	1e-04
Clathrin-mediated endocytosis	5	10.9×	2e-03
Signaling by Rho GTPases	9	7.9×	1e-04
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	9	7.7×	1e-04
Infectious disease	7	4.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	144
Likely benign	12
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1723883	NM_001308142.2(MRTFB):c.310C>G (p.Arg104Gly)	Pathogenic
1723884	NM_001308142.2(MRTFB):c.271G>C (p.Ala91Pro)	Pathogenic
3359240	NM_001308142.2(MRTFB):c.310C>A (p.Arg104=)	Pathogenic

SpliceAI

4224 predictions. Top by Δscore:

Variant	Effect	Δscore
16:14208545:G:GT	donor_gain	1.0000
16:14210240:C:G	acceptor_gain	1.0000
16:14210241:A:AG	acceptor_gain	1.0000
16:14210242:G:GG	acceptor_gain	1.0000
16:14210242:GT:G	acceptor_gain	1.0000
16:14210396:GTT:G	donor_gain	1.0000
16:14210452:GCACC:G	donor_gain	1.0000
16:14212352:A:AG	acceptor_gain	1.0000
16:14212353:G:GG	acceptor_gain	1.0000
16:14212407:AGAG:A	donor_loss	1.0000
16:14212408:GA:G	donor_gain	1.0000
16:14212409:AGT:A	donor_loss	1.0000
16:14212410:G:GG	donor_gain	1.0000
16:14212411:T:TC	donor_loss	1.0000
16:14213541:A:AG	acceptor_gain	1.0000
16:14213541:AAAGA:A	acceptor_loss	1.0000
16:14213542:A:G	acceptor_gain	1.0000
16:14213543:A:G	acceptor_gain	1.0000
16:14213543:AGAC:A	acceptor_loss	1.0000
16:14213544:G:GA	acceptor_gain	1.0000
16:14213544:GA:G	acceptor_gain	1.0000
16:14213544:GACT:G	acceptor_gain	1.0000
16:14213616:AGAAG:A	donor_loss	1.0000
16:14213617:GAAGG:G	donor_loss	1.0000
16:14213618:AAGGT:A	donor_loss	1.0000
16:14213619:AGGTA:A	donor_loss	1.0000
16:14213620:GG:G	donor_loss	1.0000
16:14213621:GTA:G	donor_loss	1.0000
16:14217124:A:AG	acceptor_gain	1.0000
16:14217125:G:GT	acceptor_gain	1.0000

AlphaMissense

7170 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017514 (16:14086960 T>C,G), RS1000031293 (16:14260224 TAAAAG>T), RS1000038937 (16:14230682 G>A), RS1000047654 (16:14263866 C>G,T), RS1000067474 (16:14172888 G>A), RS1000077158 (16:14093615 A>G), RS1000085770 (16:14136549 T>A), RS1000095023 (16:14010933 T>C), RS1000102777 (16:14066819 A>G), RS1000105638 (16:14100899 A>G), RS1000115505 (16:14219613 A>G), RS1000119800 (16:14018305 A>G), RS1000130476 (16:14240388 G>A), RS1000137314 (16:14249269 G>C), RS1000168864 (16:14257899 A>G)

Disease associations

OMIM: gene MIM:609463 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant

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

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000817_40	Height	1.000000e-11
GCST000880_34	Menarche (age at onset)	4.000000e-09
GCST002426_1	Puberty onset (genital enlargement)	9.000000e-09
GCST002500_29	QT interval	3.000000e-13
GCST002541_105	Menarche (age at onset)	7.000000e-16
GCST002702_78	Height	5.000000e-10
GCST003983_38	Male-pattern baldness	8.000000e-09
GCST003993_28	Menarche (age at onset)	6.000000e-12
GCST003994_9	Age at voice drop	7.000000e-14
GCST006631_23	Nicotine dependence and major depression (severity of comorbidity)	5.000000e-06
GCST006631_24	Nicotine dependence and major depression (severity of comorbidity)	2.000000e-06
GCST008839_15	Height	6.000000e-20
GCST009391_1278	Metabolite levels	5.000000e-06
GCST010796_1652	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_1653	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_1654	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-10
GCST010796_1655	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_1656	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_1657	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_1658	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1659	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4602	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-11
GCST010796_4603	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4604	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_4605	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010796_4606	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_4607	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_4608	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_4609	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-10
GCST010796_4610	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0005677	puberty onset measurement
EFO:0004682	QT interval
EFO:0007888	age at voice drop
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0010546	uridine measurement
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	3
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
2-butenal	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone	affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
obeticholic acid	decreases expression	1
licochalcone B	decreases expression	1
MK-8776	increases expression	1
Resveratrol	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Melphalan	decreases expression	1

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