DEAF1

DEAF1 transcription factor, the group of Zinc fingers MYND-type

Basic information

Region (hg38): 11:644233-707118

Links

ENSG00000177030NCBI:10522OMIM:602635HGNC:14677Uniprot:O75398AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • intellectual disability, autosomal dominant 24 (Definitive), mode of inheritance: AD
  • intellectual disability, autosomal dominant 24 (Strong), mode of inheritance: AD
  • intellectual disability-epilepsy-extrapyramidal syndrome (Moderate), mode of inheritance: AR
  • autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
  • intellectual disability-epilepsy-extrapyramidal syndrome (Supportive), mode of inheritance: AR
  • intellectual disability, autosomal dominant 24 (Strong), mode of inheritance: AD
  • intellectual disability-epilepsy-extrapyramidal syndrome (Strong), mode of inheritance: AR
  • complex neurodevelopmental disorder (Strong), mode of inheritance: Semidominant
  • intellectual disability-epilepsy-extrapyramidal syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Vulto-van Silfout-de Vries syndrome; Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizuresAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Neurologic21076407; 23020937; 24726472; 26048982

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DEAF1 gene.

  • not_provided (817 variants)
  • Inborn_genetic_diseases (96 variants)
  • Intellectual_disability,_autosomal_dominant_24 (71 variants)
  • DEAF1-related_disorder (39 variants)
  • Intellectual_disability-epilepsy-extrapyramidal_syndrome (35 variants)
  • not_specified (33 variants)
  • Intellectual_disability (6 variants)
  • Autism_spectrum_disorder (3 variants)
  • See_cases (3 variants)
  • Neurodevelopmental_delay (2 variants)
  • Tooth_malposition (1 variants)
  • Obesity (1 variants)
  • Poor_fine_motor_coordination (1 variants)
  • Attention_deficit_hyperactivity_disorder (1 variants)
  • Autism,_susceptiblity_to (1 variants)
  • Delayed_speech_and_language_development (1 variants)
  • Mandibular_prognathia (1 variants)
  • Prostate_cancer (1 variants)
  • Autism (1 variants)
  • Autosomal_dominant_non-syndromic_intellectual_disability (1 variants)
  • Malar_flattening (1 variants)
  • Developmental_disorder (1 variants)
  • Thin_upper_lip_vermilion (1 variants)
  • Floppy_infant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DEAF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021008.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
209
clinvar
9
clinvar
222
missense
18
clinvar
40
clinvar
368
clinvar
27
clinvar
4
clinvar
457
nonsense
8
clinvar
9
clinvar
3
clinvar
20
start loss
1
1
frameshift
16
clinvar
6
clinvar
9
clinvar
1
clinvar
32
splice donor/acceptor (+/-2bp)
3
clinvar
9
clinvar
1
clinvar
13
Total 45 64 386 237 13

Highest pathogenic variant AF is 0.0000198457

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DEAF1protein_codingprotein_codingENST00000382409 1262483
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0003410.9981257300181257480.0000716
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.502513270.7670.00002233599
Missense in Polyphen73133.810.545571383
Synonymous-0.5411561481.060.00001231179
Loss of Function2.691024.30.4110.00000134283

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00008670.0000867
Ashkenazi Jewish0.00009930.0000992
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0001230.000123
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Transcription factor that binds to sequence with multiple copies of 5'-TTC[CG]G-3' present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) 5'- AGGGTTCACCGAAAGTTCA-3'. Activates the proenkephalin gene independently of promoter binding, probably through protein- protein interaction. When secreted, behaves as an inhibitor of cell proliferation, by arresting cells in the G0 or G1 phase. Required for neural tube closure and skeletal patterning. Regulates epithelial cell proliferation and side-branching in the mammary gland. Controls the expression of peripheral tissue antigens in pancreatic lymph nodes. Isoform 1 displays greater transcriptional activity than isoform 4. Isoform 4 may inhibit transcriptional activity of isoform 1 by interacting with isoform 1 and retaining it in the cytoplasm. Transcriptional activator of EIF4G3. {ECO:0000269|PubMed:10521432, ECO:0000269|PubMed:11427895, ECO:0000269|PubMed:11705868, ECO:0000269|PubMed:18826651, ECO:0000269|PubMed:19668219, ECO:0000269|PubMed:24726472}.;
Disease
DISEASE: Mental retardation, autosomal dominant 24 (MRD24) [MIM:615828]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21076407, ECO:0000269|PubMed:24726472}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dyskinesia, seizures, and intellectual developmental disorder (DYSEIDD) [MIM:617171]: A neurodevelopmental disorder characterized by psychomotor delay, epilepsy, intellectual disability, speech impairment and dyskinesia of the limbs. Patients also manifest autistic features and other behavioral abnormalities. DYSEIDD transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:26048982}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

pRec
0.100

Intolerance Scores

loftool
0.559
rvis_EVS
-0.89
rvis_percentile_EVS
10.43

Haploinsufficiency Scores

pHI
0.161
hipred
N
hipred_score
0.411
ghis
0.623

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.980

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Deaf1
Phenotype
mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;behavioral fear response;neural tube closure;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;germ cell development;visual learning;anatomical structure morphogenesis;regulation of mammary gland epithelial cell proliferation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;embryonic skeletal system development
Cellular component
fibrillar center;extracellular region;nucleus;transcription factor complex;cytoplasm
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 factor activity;protein binding;metal ion binding