MYT1L

Chr 2

myelin transcription factor 1 like

Also known as: MRD39, NZF1, ZC2H2C2, ZC2HC4B, myT1-L

NCBI Gene: 23040 ENSG00000186487 UniProt: Q9UL68

This gene encodes a zinc finger transcription factor that functions in developing mammalian central nervous system and can convert fibroblasts into induced neuronal cells capable of generating action potentials. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder and autism spectrum disorder. The gene is extremely intolerant to loss-of-function variation, supporting haploinsufficiency as the mechanism of pathogenicity.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.09

Clinical Summary— MYT1L

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Gene-Disease Validity (ClinGen)

syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

113 unique Pathogenic / Likely Pathogenic· 245 VUS of 621 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 6.71

OE 0.02 (0.01–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

4.77Z-score

OE missense 0.50 (0.46–0.55)

365 obs / 727.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.09)

0≤0.351.4

Missense OE?0.50 (0.46–0.55)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 1 / 54.4Missense obs/exp: 365 / 727.0Syn Z: 2.25

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMYT1L-related intellectual developmental syndromeLOFAD

This gene — mechanism propensity

0.2399th %ile

GOF

0.1899th %ile

LOF

0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 69% of P/LP variants are LoF · LOEUF 0.09 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFMoreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 25232846 ↗

ClinVar Variant Classifications

621 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58

Likely Pathogenic55

VUS245

Likely Benign139

Benign100

Conflicting12

Pathogenic

Likely Pathogenic

245

VUS

139

Likely Benign

100

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	53	4	0	1	58
Likely Pathogenic	25	27	3	0	55
VUS	3	217	23	2	245
Likely Benign	0	21	47	71	139
Benign	0	6	78	16	100
Conflicting	—				12
Total	81	275	151	90	609

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

52 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap MYT1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →