DEAF1

Chr 11ARAD

DEAF1 transcription factor

Also known as: MRD24, NEDHELS, NUDR, SPN, VSVS, ZMYND5

NCBI Gene: 10522ENSG00000177030UniProt: O75398

This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizuresMIM #617171
AR
Vulto-van Silfout-de Vries syndromeMIM #615828
AD
575
ClinVar variants
49
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— DEAF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 334 VUS of 575 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.000
Z-score 2.69
OE 0.41 (0.25–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.50Z-score
OE missense 0.77 (0.69–0.85)
251 obs / 327.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.25–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 10 / 24.3Missense obs/exp: 251 / 327.2Syn Z: -0.54

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic24
VUS334
Likely Benign186
Conflicting6
25
Pathogenic
24
Likely Pathogenic
334
VUS
186
Likely Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
6
9
0
25
Likely Pathogenic
6
12
6
0
24
VUS
6
271
54
3
334
Likely Benign
0
7
68
111
186
Benign
0
0
0
0
0
Conflicting
—6
Total22296137114575

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

View in ClinVar →

Protein Context — Lollipop Plot

DEAF1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DEAF1-related autism, intellectual disability, basal ganglia dysfunction and epilepsy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

DEAF1-related intellectual developmental disorder

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures

MIM #617171

Molecular basis of disorder known

Autosomal recessive

Vulto-van Silfout-de Vries syndrome

MIM #615828

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo and biallelic DEAF1 variants cause a phenotypic spectrum.
Nabais Sá MJ et al.·Genet Med
2019
Functional analysis of novel DEAF1 variants identified through clinical exome sequencing expands DEAF1-associated neurodevelopmental disorder (DAND) phenotype.
Chen L et al.·Hum Mutat
2017Functional
Novel homozygous DEAF1 variant suspected in causing white matter disease, intellectual disability, and microcephaly.
Faqeih EA et al.·Am J Med Genet A
2014Case report
De novo variants of DEAF1 cause intellectual disability in six Chinese patients.
Chen S et al.·Clin Chim Acta
2021Cohort
Sleep disturbances associated with DEAF1 pathogenic variants.
Guerreiro P et al.·J Clin Sleep Med
2025
Functions of SMYD proteins in biological processes: What do we know? An updated review.
Rueda-Robles A et al.·Arch Biochem Biophys
2021Review
A novel autosomal recessive DEAF1 nonsense variant: expanding the clinical phenotype.
Andoni T et al.·Clin Dysmorphol
2020Case report
Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes.
Yip L et al.·Nat Immunol
2009
The biophysical and biochemical properties of the autoimmune regulator (AIRE) protein.
Perniola R et al.·Biochim Biophys Acta
2014Review
Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.
Vulto-van Silfhout AT et al.·Am J Hum Genet
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools