MYT1L

Chr 2AD

myelin transcription factor 1 like

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

NCBI Gene: 23040ENSG00000186487UniProt: Q9UL68

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]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 39MIM #616521
AD
3
Active trials
51
Pathogenic / LP
290
ClinVar variants
20
Pubs (1 yr)
4.8
Missense Z· constrained
0.09
LOEUF· LoF intolerant
Clinical Summary— MYT1L
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
51 Pathogenic / Likely Pathogenic· 185 VUS of 290 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

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 OE0.02 (0.01–0.09)
0≤0.351.4
Missense OE0.50 (0.46–0.55)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 1 / 54.4Missense obs/exp: 365 / 727.0Syn Z: 2.25
LOF
DN
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 · 39% of P/LP variants are LoF · LOEUF 0.09

Literature Evidence

LOFMoreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.PMID:25232846

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

ClinVar Variant Classifications

290 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic20
VUS185
Likely Benign45
Benign6
Conflicting3
31
Pathogenic
20
Likely Pathogenic
185
VUS
45
Likely Benign
6
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
16
0
31
Likely Pathogenic
6
9
5
0
20
VUS
1
151
32
1
185
Likely Benign
0
13
12
20
45
Benign
0
0
6
0
6
Conflicting
—3
Total211747121290

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

View in ClinVar →

MYT1L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MYT1L-related intellectual developmental syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients