MYT1L

myelin transcription factor 1 like, the group of Zinc fingers C2H2C-type

Basic information

Region (hg38): 2:1789112-2331664

Links

ENSG00000186487 ∙ NCBI:23040 ∙ OMIM:613084 ∙ HGNC:7623 ∙ Uniprot:Q9UL68 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 39 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 39 (Strong), mode of inheritance: AD
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 39 (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 39	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21990140; 23033978; 23160955; 25232846; 26240977; 30055078

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYT1L gene.

• not provided (301 variants)
• Intellectual disability, autosomal dominant 39 (70 variants)
• Inborn genetic diseases (28 variants)
• Intellectual disability (11 variants)
• not specified (11 variants)
• MYT1L-related condition (5 variants)
• Neurodevelopmental disorder (3 variants)
• Neurodevelopmental delay (2 variants)
• Autism spectrum disorder (2 variants)
• See cases (2 variants)
• Autism (1 variants)
• Syndromic intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYT1L gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		2	45	22	70
missense	3	18	93	12	4	130
nonsense	14	3				17
start loss			2			2
frameshift	12	7	1			20
inframe indel			8	2	2	12
splice donor/acceptor (+/-2bp)	2	1				3
splice region		2	7	4	1	14
non coding			4	36	77	117
Total	32	29	110	95	105

Variants in MYT1L

This is a list of pathogenic ClinVar variants found in the MYT1L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-1791881-C-T			Uncertain significance (Jul 08, 2022)
2-1791884-T-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
2-1791896-TTA-T			Uncertain significance (Jan 21, 2022)
2-1791899-T-C		Intellectual disability, autosomal dominant 39	Uncertain significance (Jul 14, 2020)
2-1791952-T-C			Uncertain significance (Jan 19, 2022)
2-1792001-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
2-1792276-C-T			Likely benign (Feb 15, 2020)
2-1792348-G-T			Uncertain significance (Sep 14, 2021)
2-1792367-C-T			Uncertain significance (Aug 01, 2023)
2-1792383-C-G			Uncertain significance (Nov 13, 2019)
2-1792454-A-G		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
2-1792456-C-T			Likely benign (Apr 01, 2022)
2-1792691-T-C			Likely benign (Jul 21, 2019)
2-1792707-T-C			Likely benign (Apr 09, 2019)
2-1792732-T-G			Benign (Aug 10, 2018)
2-1801553-A-G			Likely benign (Oct 28, 2019)
2-1801657-C-T			Benign (Jul 11, 2020)
2-1801658-G-A			Benign (Aug 10, 2018)
2-1801717-A-G			Benign (Aug 10, 2018)
2-1801726-C-T		MYT1L-related disorder	Uncertain significance (Sep 29, 2022)
2-1801758-T-G			Uncertain significance (Jan 13, 2023)
2-1801772-T-A		Autism	Uncertain significance (Jul 26, 2022)
2-1801776-T-G		Intellectual disability, autosomal dominant 39	Uncertain significance (Jul 18, 2019)
2-1801804-A-C		Inborn genetic diseases	Likely benign (Jun 13, 2022)
2-1801913-T-C			Likely benign (Dec 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYT1L	protein_coding	protein_coding	ENST00000428368	20	542148

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.36e-8	124643	0	2	124645	0.00000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.77	365	727	0.502	0.0000456	7928
Missense in Polyphen		91	308	0.29545		3271
Synonymous	2.25	254	304	0.836	0.0000229	2078
Loss of Function	6.71	1	54.4	0.0184	0.00000270	674

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000889	0.00000885
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000250|UniProtKB:P97500}.
• Disease: DISEASE: Mental retardation, autosomal dominant 39 (MRD39) [MIM:616521]: A form of mental retardation, 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. {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23160955}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.116

Intolerance Scores

• rvis_EVS: -1.51
• rvis_percentile_EVS: 3.54

Haploinsufficiency Scores

• pHI: 0.307
• hipred: Y
• hipred_score: 0.755
• ghis: 0.628

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.336

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Myt1l

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription by RNA polymerase II;nervous system development;neuron differentiation;positive regulation of transcription by RNA polymerase II;neuron fate commitment;neuron fate specification;neuron development
• Cellular component: nucleus;chromosome
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;zinc ion binding