MYT1L

Summary

MYT1L (myelin transcription factor 1 like, HGNC:7623) is a protein-coding gene on chromosome 2p25.3, encoding Myelin transcription factor 1-like protein (Q9UL68). Transcription factor that plays a key role in neuronal differentiation by specifically repressing expression of non-neuronal genes during neuron differentiation. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the zinc finger superfamily of transcription factors whose expression, thus far, has been found only in neuronal tissues. The encoded protein belongs to a novel class of cystein-cystein-histidine-cystein zinc finger proteins that function in the developing mammalian central nervous system. Forced expression of this gene in combination with the basic helix-loop-helix transcription factor NeuroD1 and the transcription factors POU class 3 homeobox 2 and achaete-scute family basic helix-loop-helix transcription factor 1 can convert fetal and postnatal human fibroblasts into induced neuronal cells, which are able to generate action potentials. Mutations in this gene have been associated with an autosomal dominant form of cognitive disability and with autism spectrum disorder. Alternative splicing results in multiple variants.

Source: NCBI Gene 23040 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 24
• Clinical variants (ClinVar): 652 total — 61 pathogenic, 50 likely-pathogenic
• Phenotypes (HPO): 85
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001303052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7623
Approved symbol	MYT1L
Name	myelin transcription factor 1 like
Location	2p25.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1106, NZF1, ZC2HC4B, ZC2H2C2
Ensembl gene	ENSG00000186487
Ensembl biotype	protein_coding
OMIM	613084
Entrez	23040

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 42 protein_coding, 13 protein_coding_CDS_not_defined, 12 retained_intron, 4 nonsense_mediated_decay

ENST00000399157, ENST00000399161, ENST00000407844, ENST00000428368, ENST00000460585, ENST00000470954, ENST00000471668, ENST00000476547, ENST00000479156, ENST00000485348, ENST00000485547, ENST00000490585, ENST00000602387, ENST00000644820, ENST00000647604, ENST00000647618, ENST00000647687, ENST00000647694, ENST00000647697, ENST00000647738, ENST00000647755, ENST00000647848, ENST00000648148, ENST00000648299, ENST00000648316, ENST00000648318, ENST00000648339, ENST00000648366, ENST00000648430, ENST00000648465, ENST00000648478, ENST00000648486, ENST00000648568, ENST00000648598, ENST00000648627, ENST00000648643, ENST00000648665, ENST00000648688, ENST00000648753, ENST00000648814, ENST00000648885, ENST00000648913, ENST00000648928, ENST00000648931, ENST00000648933, ENST00000648943, ENST00000649092, ENST00000649149, ENST00000649207, ENST00000649260, ENST00000649313, ENST00000649587, ENST00000649618, ENST00000649641, ENST00000649646, ENST00000649663, ENST00000649709, ENST00000649741, ENST00000649810, ENST00000649840, ENST00000649898, ENST00000650081, ENST00000650174, ENST00000650253, ENST00000650399, ENST00000650485, ENST00000650560, ENST00000650589, ENST00000650593, ENST00000689939, ENST00000892482

RefSeq mRNA: 10 — MANE Select: NM_001303052 NM_001303052, NM_001329844, NM_001329845, NM_001329846, NM_001329847, NM_001329848, NM_001329849, NM_001329851, NM_001329852, NM_015025

CCDS: CCDS46222, CCDS77378, CCDS92704, CCDS92706, CCDS92707, CCDS92709

Canonical transcript exons

ENST00000647738 — 25 exons

Exon	Start	End
ENSE00001190576	1792321	1792464
ENSE00001190582	1801696	1801799
ENSE00001190586	1809076	1809167
ENSE00001425054	1997191	1997347
ENSE00001426881	2053978	2054123
ENSE00001430627	2172872	2172988
ENSE00001433232	2284404	2284503
ENSE00001536837	1922286	1923263
ENSE00001599252	1912020	1912110
ENSE00001651145	1903080	1903294
ENSE00001694020	1942982	1943334
ENSE00001715295	1917205	1917339
ENSE00001739583	1979521	1979554
ENSE00001764262	1851641	1851703
ENSE00001904770	1789113	1792007
ENSE00002307163	1979723	1979777
ENSE00003461831	1910240	1910347
ENSE00003514549	1887488	1887609
ENSE00003530137	1979165	1979227
ENSE00003566367	1889241	1889477
ENSE00003584352	1840760	1840843
ENSE00003595162	1886539	1886607
ENSE00003612628	1839149	1839370
ENSE00003689672	1892037	1892287
ENSE00003833736	2330967	2331275

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 98.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.4840 / max 1421.0078, expressed in 179 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26679	3.5879	149
26682	0.7085	94
26668	0.4838	95
26671	0.4607	94
26681	0.4378	88
26675	0.3040	80
26667	0.2148	73
26672	0.1875	72
26666	0.1537	51
26665	0.1302	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.79	gold quality
cortical plate	UBERON:0005343	98.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.45	gold quality
CA1 field of hippocampus	UBERON:0003881	98.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.31	gold quality
primary visual cortex	UBERON:0002436	97.30	gold quality
orbitofrontal cortex	UBERON:0004167	97.28	gold quality
postcentral gyrus	UBERON:0002581	97.26	gold quality
occipital lobe	UBERON:0002021	97.16	gold quality
parietal lobe	UBERON:0001872	97.15	gold quality
middle temporal gyrus	UBERON:0002771	96.98	gold quality
superior frontal gyrus	UBERON:0002661	96.63	gold quality
entorhinal cortex	UBERON:0002728	96.45	gold quality
pons	UBERON:0000988	95.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.83	gold quality
prefrontal cortex	UBERON:0000451	94.52	gold quality
ganglionic eminence	UBERON:0004023	94.38	gold quality
lateral globus pallidus	UBERON:0002476	94.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.04	gold quality
frontal cortex	UBERON:0001870	93.85	gold quality
cerebral cortex	UBERON:0000956	93.57	gold quality
neocortex	UBERON:0001950	93.21	gold quality
cerebellum	UBERON:0002037	93.06	gold quality
cerebellar hemisphere	UBERON:0002245	92.95	gold quality
cerebellar cortex	UBERON:0002129	92.92	gold quality
telencephalon	UBERON:0001893	92.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.35	gold quality
substantia nigra pars compacta	UBERON:0001965	92.15	gold quality
Ammon’s horn	UBERON:0001954	91.99	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2573.86
E-GEOD-75140	yes	1737.80
E-HCAD-35	yes	78.41
E-HCAD-5	yes	47.98
E-HCAD-25	yes	44.78
E-GEOD-137537	yes	9.22
E-ANND-3	yes	9.20
E-ENAD-27	no	267.54
E-MTAB-7606	no	16.81
E-GEOD-93593	no	13.41

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
HES1	Repression
YAP1	Repression

JASPAR motifs

Motif	Name	Family
MA2682.1	MYT1L	MYT

JASPAR matrix evidence (PMIDs): PMID:28379941

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

226 targeting MYT1L, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
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-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6888-3P	99.97	65.95	1170

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 26)

• results indicate that MYT1L may be a potential risk gene for major depressive disorder in the Chinese Han population (PMID:21048971)
• Findings suggest that MYT1L may represent a susceptibility gene for schizophrenia in the Han Chinese population and show that a specific SNP may increase susceptibility in females. (PMID:21923761)
• MYT1L deletion gives a nonspecific clinical phenotype shared by patients with 2p25.3 deletions, with only intellectual disability and obesity/overweight being present in all patients. (PMID:21990140)
• Results from this study indicate that the 2p25.3 duplication disrupting PXDN and MYT1L is a potential autism-causing variant in the pedigree reported here and should receive further consideration as a candidate for autism (PMID:22157634)
• A meta-analysis of four recently published studies that together provide strong evidence for an association between variably sized microduplications involving the MYT1L gene and schizophrenia. (PMID:22547139)
• MYT1L and the SNTG2 genes within the reported region could probably relate to the phenotypic discordance of the monozygotic twins. (PMID:23061379)
• Data indicate that reintroduction of A2BP1 or Myt1L in glioblastoma multiforme (GBM) cell lines and glioma stem cells profoundly inhibited tumorigenesis. (PMID:23918370)
• MYT1L rs17039396 variants are associated with clinical outcome in gastric cancer. (PMID:24015200)
• Report shows that the first histidine of Cys2His2Cys domains is involved in a functionally important hydrogen bonding interaction. (PMID:24820620)
• Our data strongly strengthen the hypothesis that MYT1L is the causal gene for the observed syndromal intellectual disability. (PMID:25232846)
• Haplotype-dependent allele-specific methylation of MYT1L gene is associated with neurological disorders. (PMID:27153397)
• (1) MYT1L is required for neuronal differentiation and identified ID1 as a target. (2) Although MYT1L prevented expression of ID1, it induced expression of a large number of terminal differentiation genes. (3) Consistently, expression of MYT1L in the human brain coincided with neuronal maturation and inversely correlated with that of ID1 and ID3 throughout the lifespan. (PMID:28470180)
• This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus (PMID:28859103)
• wide analyses of the effects of Myt1 and Myt1l expression in a glioblastoma cell line suggest that the two proteins have largely similar effects on endogenous gene expression. Transcriptional repression is likely mediated by binding to DNA via the known consensus site, whereas this site is not associated with the transcriptional start sites of genes with higher expression in the presence of Myt1 or Myt1l. (PMID:29291346)
• Myt1l was a critical mediator of induced neuron cell reprogramming. (PMID:29453933)
• Our finding supports the association of MYT1L mutations with early-onset syndromic obesity. The identification of novel monogenic forms of childhood-onset obesity will provide insights to the involved genetic and biologic pathways. (PMID:30055078)
• Here we demonstrate that re-expression of Myt1 or Myt1l in glioblastoma (GBM) cell lines slows proliferation, that expression of both is lower in more aggressive sub-types of glioma, and that reduced expression correlates with poor prognosis in both GBM and low grade glioma, and our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth. (PMID:30312684)
• The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network. (PMID:31522595)
• Nine newly identified individuals refine the phenotype associated with MYT1L mutations. (PMID:32065501)
• MYT1L: A systematic review of genetic variation encompassing schizophrenia and autism. (PMID:32267091)
• The neuronal transcription factor Myt1L interacts via a conserved motif with the PAH1 domain of Sin3 to recruit the Sin3L/Rpd3L histone deacetylase complex. (PMID:32391601)
• A web-based survey on various symptoms of computer vision syndrome and the genetic understanding based on a multi-trait genome-wide association study. (PMID:33941792)
• MYT1L-associated neurodevelopmental disorder: description of 40 new cases and literature review of clinical and molecular aspects. (PMID:34748075)
• Co-Occurrence of Fragile X Syndrome with a Second Genetic Condition: Three Independent Cases of Double Diagnosis. (PMID:34946857)
• MYT1L haploinsufficiency in human neurons and mice causes autism-associated phenotypes that can be reversed by genetic and pharmacologic intervention. (PMID:36782060)
• 2p25.3 microduplications involving MYT1L: further phenotypic characterization through an assessment of 16 new cases and a literature review. (PMID:37188826)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000116393
mus_musculus	Myt1l	ENSMUSG00000061911
rattus_norvegicus	Myt1l	ENSRNOG00000004269
drosophila_melanogaster	Pits	FBGN0030400
caenorhabditis_elegans	ztf-11	WBGENE00009939
caenorhabditis_elegans		WBGENE00010867

Paralogs (5): IRF2BPL (ENSG00000119669), ST18 (ENSG00000147488), IRF2BP2 (ENSG00000168264), IRF2BP1 (ENSG00000170604), MYT1 (ENSG00000196132)

Protein

Protein identifiers

Myelin transcription factor 1-like protein — Q9UL68 (reviewed: Q9UL68)

All UniProt accessions (37): A0A2R8YF72, A0A3B3IRF0, A0A3B3IRJ2, A0A3B3IRK4, A0A3B3IRM3, A0A3B3IRQ0, A0A3B3IRR4, A0A3B3IRT9, A0A3B3IRX0, A0A3B3IRX5, A0A3B3IS14, A0A3B3IS21, A0A3B3IS61, A0A3B3IS77, A0A3B3IS97, A0A3B3ISB6, A0A3B3ISG9, A0A3B3ISI4, A0A3B3ISN1, A0A3B3ISN3, A0A3B3ISP2, A0A3B3ISU4, Q9UL68, A0A3B3ISU9, A0A3B3ISW5, A0A3B3IT20, A0A3B3ITJ8, A0A3B3ITL3, A0A3B3ITS6, A0A3B3ITT2, A0A3B3IU66, A0A3B3IU83, A0A3B3IUE2, A0A8I5KQG8, H7BYU4, Q49A74, R4GMY9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that plays a key role in neuronal differentiation by specifically repressing expression of non-neuronal genes during neuron differentiation. In contrast to other transcription repressors that inhibit specific lineages, mediates repression of multiple differentiation programs. Also represses expression of negative regulators of neurogenesis, such as members of the Notch signaling pathway, including HES1. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Directly binds the 5’-AAGTT-3’ core motif present on the promoter of target genes and represses transcription by recruiting a multiprotein complex containing SIN3B. The 5’-AAGTT-3’ core motif is absent from the promoter of neural genes.

Subunit / interactions. Interacts with SIN3B.

Subcellular location. Nucleus. Chromosome.

Disease relevance. Intellectual developmental disorder, autosomal dominant 39 (MRD39) [MIM:616521] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD39 patients show delayed psychomotor development and autistic features. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the MYT1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UL68-1	1	yes
Q9UL68-3	3
Q9UL68-4	4

RefSeq proteins (10): NP_001289981, NP_001316773, NP_001316774, NP_001316775, NP_001316776, NP_001316777, NP_001316778, NP_001316780, NP_001316781, NP_055840 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002515	Znf_C2H2C	Repeat
IPR013681	Myelin_TF	Domain
IPR036060	Znf_C2H2C_sf	Homologous_superfamily

Pfam: PF01530, PF08474

UniProt features (55 total): binding site 24, region of interest 7, compositionally biased region 7, zinc finger region 6, sequence conflict 5, splice variant 3, chain 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL68-F1	55.73	0.05

Functional residue map

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

Ligand- & substrate-binding residues (24): 31; 36; 49; 55; 506; 511; 524; 530; 550; 555; 568; 574 …

Post-translational modifications (1): 250

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 338 (showing top): GNF2_RTN1, chr2p25, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, AAGCCAT_MIR135A_MIR135B, GOBP_NEUROGENESIS, GOBP_NEURON_FATE_SPECIFICATION, ATTCTTT_MIR186, SANSOM_APC_TARGETS_DN, GOBP_NEURON_FATE_COMMITMENT, GOBP_CELL_FATE_SPECIFICATION, MODULE_48, MODULE_95, GOBP_CELL_FATE_COMMITMENT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CHEN_NEUROBLASTOMA_COPY_NUMBER_GAINS

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), neuron differentiation (GO:0030182), neuron fate commitment (GO:0048663), neuron fate specification (GO:0048665), neuron development (GO:0048666), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (12): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), retinoic acid-responsive element binding (GO:0044323), cobalt ion binding (GO:0050897), metal ion sequestering activity (GO:0140487), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
neuron differentiation	2
positive regulation of DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
transition metal ion binding	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
system development	1
cell differentiation	1
generation of neurons	1
cell fate commitment	1
cell fate specification	1
neuron fate commitment	1
cell development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription coregulator activity	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
metal ion binding	1
molecular sequestering activity	1
nucleic acid binding	1
transcription regulator activity	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYT1L	POU3F2	P20265	969
MYT1L	ASCL1	P50553	961
MYT1L	POU3F3	P20264	826
MYT1L	DLX1	P56177	745
MYT1L	NEUROD1	Q13562	721
MYT1L	DLX2	Q07687	713
MYT1L	NEUROG2	Q9H2A3	695
MYT1L	LMX1B	O60663	688
MYT1L	NKX2-2	O95096	688
MYT1L	PHF20	Q9BVI0	662
MYT1L	NEUROD2	Q15784	652
MYT1L	SNTG2	Q9NY99	622
MYT1L	RNF31	Q96EP0	602
MYT1L	DLL1	O00548	598
MYT1L	NEUROG3	Q9Y4Z2	595

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MYT1L	SNRPA	psi-mi:“MI:0915”(physical association)	0.400
MYT1L	CDC5L	psi-mi:“MI:0915”(physical association)	0.000
MYT1L	DISC1	psi-mi:“MI:0915”(physical association)	0.000
MYT1L	TNIK	psi-mi:“MI:0915”(physical association)	0.000
CLU	MYT1L	psi-mi:“MI:0915”(physical association)	0.000
TNIK	MYT1L	psi-mi:“MI:0915”(physical association)	0.000
DISC1	MYT1L	psi-mi:“MI:0915”(physical association)	0.000
CDC5L	MYT1L	psi-mi:“MI:0915”(physical association)	0.000
MYT1L	NR4A1	psi-mi:“MI:0915”(physical association)	0.000
MYT1L	PCBD1	psi-mi:“MI:0915”(physical association)	0.000
DYRK1A	MYT1L	psi-mi:“MI:0915”(physical association)	0.000
PCNT	MYT1L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (67): MYT1L (Reconstituted Complex), TGFBR1 (Reconstituted Complex), MYT1L (Proximity Label-MS), MYT1L (Two-hybrid), MYT1L (Two-hybrid), MYT1L (Affinity Capture-MS), CUX1 (Affinity Capture-MS), LIG3 (Affinity Capture-MS), LMNA (Affinity Capture-MS), MKI67 (Affinity Capture-MS), MED1 (Affinity Capture-MS), PRKDC (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RRBP1 (Affinity Capture-MS), TOP2A (Affinity Capture-MS)

ESM2 similar proteins: A7MB80, A8WL28, B5YWI0, B7UM99, C6UYL8, C8UFK8, D3QW22, E1WAC6, O02828, O10270, O85041, P03274, P09687, P0CL52, P0DJ90, P0DJ91, P0DJ92, P23460, P24937, P29172, P35988, P37801, P37806, P57786, P70475, P74849, P78347, P81584, P83592, P97500, P97836, Q00131, Q09936, Q19191, Q24546, Q31HD7, Q5U2Y1, Q65954, Q6GZV6, Q6TS35

Diamond homologs: A2A5N8, B1B1A0, D3YUG0, D3YXK1, D3ZWK4, E1C2V1, O02274, O60284, O95251, P39769, P59178, P70047, P70475, P78364, P97500, Q01538, Q05BQ5, Q1JQD9, Q1RNF8, Q29L50, Q32N90, Q3MIF2, Q4V7W5, Q5DTW2, Q5R737, Q5SVQ0, Q5VUG0, Q5VXD3, Q64028, Q6DIN3, Q6P5G3, Q6SPE9, Q6SPF0, Q7Z3H4, Q80TY4, Q810T5, Q8BLB7, Q8C8Y5, Q8CFC2, Q8CHP6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MYT1L	“down-regulates quantity by repression”	YAP1	“transcriptional regulation”
MYT1L	down-regulates	Demyelination
MYT1L	“up-regulates activity”	SIN3B	binding
MYT1L	“down-regulates quantity by repression”	HES1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	61
Likely pathogenic	50
Uncertain significance	265
Likely benign	117
Benign	100

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064796	NM_001303052.2(MYT1L):c.1807del (p.Arg603fs)	Pathogenic
1179233	NM_001303052.2(MYT1L):c.1-1G>T	Pathogenic
1392738	NM_001303052.2(MYT1L):c.2233G>T (p.Glu745Ter)	Pathogenic
1527726	GRCh37/hg19 2p25.3(chr2:528352-2564992)	Pathogenic
1527737	GRCh37/hg19 2p25.3(chr2:637829-1945590)	Pathogenic
1700213	NM_001303052.2(MYT1L):c.591C>G (p.Tyr197Ter)	Pathogenic
1802188	NM_001303052.2(MYT1L):c.2821C>T (p.Gln941Ter)	Pathogenic
208428	NM_001303052.2(MYT1L):c.2642+1G>A	Pathogenic
208429	NM_001303052.2(MYT1L):c.1923T>G (p.Tyr641Ter)	Pathogenic
2270857	NM_001303052.2(MYT1L):c.2670_2671del (p.Ser891fs)	Pathogenic
2429945	NM_001303052.2(MYT1L):c.2677C>T (p.Arg893Ter)	Pathogenic
2497871	NM_001303052.2(MYT1L):c.1968T>G (p.Tyr656Ter)	Pathogenic
2572327	NM_001303052.2(MYT1L):c.1996C>T (p.Gln666Ter)	Pathogenic
2573975	NM_001303052.2(MYT1L):c.181del (p.Arg61fs)	Pathogenic
2577997	NM_001303052.2(MYT1L):c.1751del (p.Lys584fs)	Pathogenic
2578844	NM_001303052.2(MYT1L):c.1174dup (p.Arg392fs)	Pathogenic
2637811	NM_001303052.2(MYT1L):c.165T>A (p.Cys55Ter)	Pathogenic
2662423	NM_001303052.2(MYT1L):c.223C>T (p.Arg75Ter)	Pathogenic
280449	NM_001303052.2(MYT1L):c.487G>T (p.Glu163Ter)	Pathogenic
280803	NM_001303052.2(MYT1L):c.2123dup (p.Ser709fs)	Pathogenic
3024337	NM_001303052.2(MYT1L):c.982G>T (p.Glu328Ter)	Pathogenic
3026857	NM_001303052.2(MYT1L):c.2450G>A (p.Trp817Ter)	Pathogenic
3056156	NM_001303052.2(MYT1L):c.503del (p.Asn168fs)	Pathogenic
3255172	NM_001303052.2(MYT1L):c.377del (p.Glu126fs)	Pathogenic
3338193	NM_001303052.2(MYT1L):c.394del (p.Glu132fs)	Pathogenic
3382527	NM_001303052.2(MYT1L):c.4G>T (p.Glu2Ter)	Pathogenic
3383976	NM_001303052.2(MYT1L):c.1543_1561dup (p.Tyr521fs)	Pathogenic
3393564	NM_001303052.2(MYT1L):c.409G>T (p.Glu137Ter)	Pathogenic
3778755	NM_001303052.2(MYT1L):c.1586G>A (p.Gly529Glu)	Pathogenic
3916762	NM_001303052.2(MYT1L):c.322del (p.Glu108fs)	Pathogenic

SpliceAI

7173 predictions. Top by Δscore:

Variant	Effect	Δscore
2:1792314:CACT:C	donor_loss	1.0000
2:1792315:ACTT:A	donor_loss	1.0000
2:1792316:CTT:C	donor_loss	1.0000
2:1792317:TTA:T	donor_loss	1.0000
2:1792318:TA:T	donor_loss	1.0000
2:1792319:A:AC	donor_gain	1.0000
2:1792319:A:T	donor_loss	1.0000
2:1792319:AC:A	donor_gain	1.0000
2:1792320:C:CC	donor_gain	1.0000
2:1792320:C:CG	donor_loss	1.0000
2:1792320:CC:C	donor_gain	1.0000
2:1792320:CCAT:C	donor_gain	1.0000
2:1792461:TAAT:T	acceptor_gain	1.0000
2:1792463:AT:A	acceptor_gain	1.0000
2:1792464:TCTG:T	acceptor_loss	1.0000
2:1792465:C:CC	acceptor_gain	1.0000
2:1792465:CTG:C	acceptor_loss	1.0000
2:1792471:C:CT	acceptor_gain	1.0000
2:1801800:CTGTA:C	acceptor_loss	1.0000
2:1801801:T:A	acceptor_loss	1.0000
2:1809164:CAAG:C	acceptor_gain	1.0000
2:1809168:C:CC	acceptor_gain	1.0000
2:1839144:CTCA:C	donor_loss	1.0000
2:1839145:TCACC:T	donor_loss	1.0000
2:1839146:CA:C	donor_loss	1.0000
2:1839148:C:CT	donor_loss	1.0000
2:1851701:CAC:C	acceptor_gain	1.0000
2:1851701:CACCT:C	acceptor_loss	1.0000
2:1851702:AC:A	acceptor_gain	1.0000
2:1851702:ACC:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002043 (2:2232685 T>C), RS1000007445 (2:1838837 A>G), RS1000008964 (2:2312373 G>A,C), RS1000010413 (2:2130136 A>C), RS1000012569 (2:2307484 A>G), RS1000024678 (2:2013287 C>T), RS1000040693 (2:2083857 G>A), RS1000041187 (2:2199821 C>T), RS1000041640 (2:2239762 C>T), RS1000050913 (2:1861513 T>C,G), RS1000054695 (2:1937277 G>A,T), RS1000057555 (2:2194607 T>C), RS1000062715 (2:2130403 C>T), RS1000066588 (2:2055101 T>C), RS1000072352 (2:1956929 T>C)

Disease associations

OMIM: gene MIM:613084 | disease phenotypes: MIM:616521, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 39	Definitive	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (6): intellectual disability, autosomal dominant 39 (MONDO:0014678), neurodevelopmental disorder (MONDO:0700092), syndromic intellectual disability (MONDO:0000508), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), autism (MONDO:0005260)

Orphanet (3): Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000107	Renal cyst
HP:0000135	Hypogonadism
HP:0000154	Wide mouth
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000293	Full cheeks
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000742	Self-mutilation
HP:0000750	Delayed speech and language development
HP:0000776	Congenital diaphragmatic hernia
HP:0000817	Reduced eye contact
HP:0000821	Hypothyroidism
HP:0000872	Hashimoto thyroiditis
HP:0001249	Intellectual disability

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000246_11	Attention deficit hyperactivity disorder	8.000000e-06
GCST001017_17	Diabetic retinopathy	3.000000e-06
GCST002559_8	Vitamin B levels in ischemic stroke	1.000000e-06
GCST002726_73	Glucose homeostasis traits	1.000000e-06
GCST002740_21	Inflammatory skin disease	6.000000e-08
GCST003075_104	Cognitive decline rate in late mild cognitive impairment	3.000000e-07
GCST003075_105	Cognitive decline rate in late mild cognitive impairment	7.000000e-09
GCST003075_84	Cognitive decline rate in late mild cognitive impairment	5.000000e-10
GCST003809_5	Response to selective serotonin reuptake inhibitors and depression	2.000000e-06
GCST003854_21	Gut microbiota (functional units)	3.000000e-08
GCST004125_15	Type 2 diabetes (age of onset)	3.000000e-06
GCST006195_82	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-09
GCST006218_87	Erosive tooth wear (severe vs non-severe)	4.000000e-08
GCST006226_12	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST006493_7	Systemic sclerosis	6.000000e-06
GCST007324_33	Adventurousness	3.000000e-08
GCST007392_1	Mitochondrial DNA copy number (white blood cells)	3.000000e-07
GCST007622_1	Impulsivity	1.000000e-07
GCST007628_2	Impulsivity (motor)	9.000000e-07
GCST007629_2	Impulsivity (non-planning)	4.000000e-07
GCST008179_9	Moderate-to-late spontaneous preterm birth	2.000000e-06
GCST008477_10	Emphysema annual change measurement in smokers (adjusted lung density)	3.000000e-06
GCST009257_11	Caudate nucleus volume	5.000000e-06
GCST010396_292	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-08

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0007710	cognitive decline measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007874	gut microbiome measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0008579	risk-taking behaviour
EFO:0006312	mitochondrial DNA measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0006917	spontaneous preterm birth
EFO:0007626	emphysema imaging measurement
EFO:0004830	caudate nucleus volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs79663562	Efficacy	3	allopurinol

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs79663562	MYT1L	3	0.00	1	allopurinol

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
bisphenol A	affects methylation, affects cotreatment, increases methylation	1
trichostatin A	affects expression, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sulforaphane	decreases expression	1
sodium arsenite	affects methylation	1
manganese chloride	increases expression	1
entinostat	decreases expression	1
clothianidin	increases expression	1
licochalcone B	decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects methylation, increases abundance	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Vehicle Emissions	affects methylation, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Estradiol	affects binding, increases expression	1
Manganese	increases expression	1
Nickel	affects expression, decreases reaction	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Smoke	increases expression	1
Tamoxifen	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4J4	SEES3-1V human MYT1L, clone1	Embryonic stem cell	Male
CVCL_A4J5	SEES3-1V human MYT1L, clone2	Embryonic stem cell	Male
CVCL_A4J6	SEES3-1V human MYT1L, clone3	Embryonic stem cell	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