DEAF1

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

Basic information

Region (hg38): 11:644232-707118

Links

ENSG00000177030 ∙ NCBI:10522 ∙ OMIM:602635 ∙ HGNC:14677 ∙ Uniprot:O75398 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vulto-van Silfout-de Vries syndrome; Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures	AD/AR	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	Craniofacial; Neurologic	21076407; 23020937; 24726472; 26048982

ClinVar

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

• not provided (577 variants)
• Inborn genetic diseases (57 variants)
• Intellectual disability, autosomal dominant 24 (42 variants)
• not specified (27 variants)
• Intellectual disability-epilepsy-extrapyramidal syndrome (25 variants)
• DEAF1-related condition (8 variants)
• Intellectual disability-epilepsy-extrapyramidal syndrome;Intellectual disability, autosomal dominant 24 (5 variants)
• Autism spectrum disorder (3 variants)
• Intellectual disability, autosomal dominant 24;Intellectual disability-epilepsy-extrapyramidal syndrome (3 variants)
• Neurodevelopmental delay (2 variants)
• See cases (2 variants)
• Intellectual disability (2 variants)
• Autism, susceptiblity to (1 variants)
• Developmental disorder (1 variants)
• DEAF1-Related Disorder (1 variants)
• 9 conditions (1 variants)
• Autosomal dominant non-syndromic intellectual disability (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.

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			3	146	11	160
missense	10	21	250	13	4	298
nonsense	5	6	4			15
start loss						0
frameshift	6	5	5			16
inframe indel		1	27		1	29
splice donor/acceptor (+/-2bp)		7	1			8
splice region		1	14	19	1	35
non coding			18	50	12	80
Total	21	40	308	209	28

Highest pathogenic variant AF is 0.00000658

Variants in DEAF1

This is a list of pathogenic ClinVar variants found in the DEAF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-644545-G-A		DEAF1-related disorder	Uncertain significance (Mar 08, 2023)
11-644556-G-A		DEAF1-related disorder	Likely benign (Oct 13, 2023)
11-644557-G-T			Uncertain significance (Feb 05, 2023)
11-644561-C-T			Likely benign (Sep 21, 2023)
11-644562-C-T			Likely benign (Jun 24, 2022)
11-644565-C-T			Likely benign (Dec 07, 2023)
11-644568-C-G		not specified	Benign (Jan 15, 2024)
11-644573-C-T		DEAF1-related disorder	Uncertain significance (Oct 03, 2023)
11-644574-G-A			Likely benign (May 08, 2021)
11-644583-C-T			Likely benign (Mar 25, 2021)
11-644585-C-T			Uncertain significance (Feb 14, 2023)
11-644586-G-A			Likely benign (Feb 16, 2023)
11-644588-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
11-644590-A-AC			Uncertain significance (Jan 15, 2023)
11-644594-C-T		See cases	Uncertain significance (Jan 10, 2024)
11-644595-G-A			Likely benign (Dec 06, 2023)
11-644595-G-C			Uncertain significance (May 08, 2022)
11-644596-T-C			Uncertain significance (Apr 03, 2023)
11-644600-C-T			Uncertain significance (Aug 14, 2023)
11-644603-G-A			Uncertain significance (Nov 01, 2023)
11-644605-A-T			Uncertain significance (Jan 24, 2024)
11-644606-C-G			Uncertain significance (Oct 12, 2022)
11-644606-C-T			Likely benign (Aug 10, 2023)
11-644606-CG-C			Uncertain significance (Nov 30, 2021)
11-644607-G-A			Likely benign (Mar 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DEAF1	protein_coding	protein_coding	ENST00000382409	12	62483

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000341	0.998	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.50	251	327	0.767	0.0000223	3599
Missense in Polyphen		73	133.81	0.54557		1383
Synonymous	-0.541	156	148	1.06	0.0000123	1179
Loss of Function	2.69	10	24.3	0.411	0.00000134	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

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

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