EBF3

EBF transcription factor 3, the group of MicroRNA protein coding host genes|IPT domain containing|Early B-cell factors

Basic information

Region (hg38): 10:129835233-129973053

Links

ENSG00000108001 ∙ NCBI:253738 ∙ OMIM:607407 ∙ HGNC:19087 ∙ Uniprot:Q9H4W6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotonia, ataxia, and delayed development syndrome (Strong), mode of inheritance: AD
• hypotonia, ataxia, and delayed development syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotonia, ataxia, and delayed development syndrome (HADDS)	AD	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; Genitourinary; Neurologic	28017370; 28017372; 28017373

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EBF3 gene.

• not provided (29 variants)
• Hypotonia, ataxia, and delayed development syndrome (18 variants)
• Inborn genetic diseases (6 variants)
• Intellectual disability;Global developmental delay;Expressive language delay;Hypotonia;Dyssynergia (1 variants)
• Isolated Pierre-Robin syndrome (1 variants)
• Hypotonia;Intellectual disability (severe) (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• See cases (1 variants)
• Dyssynergia;Global developmental delay;Hypotonia;Expressive language delay;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EBF3 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			2	20	3	25
missense	9	25	63	6		103
nonsense	14	2				16
start loss						0
frameshift	13	8	2			23
inframe indel	1	1	4			6
splice donor/acceptor (+/-2bp)	8		2			10
splice region	1		8	7		16
non coding		1	1	4	1	7
Total	45	37	74	30	4

Variants in EBF3

This is a list of pathogenic ClinVar variants found in the EBF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-129837933-A-G		not specified	Uncertain significance (May 13, 2022)
10-129837935-T-A			Likely benign (Oct 09, 2018)
10-129837958-T-C		Hypotonia, ataxia, and delayed development syndrome	Uncertain significance (Sep 19, 2020)
10-129837960-G-A		Hypotonia, ataxia, and delayed development syndrome	Uncertain significance (Mar 29, 2024)
10-129840237-A-C		Intellectual disability	Likely benign (Jan 01, 2019)
10-129840255-A-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
10-129840260-C-T		Inborn genetic diseases	Uncertain significance (Feb 14, 2024)
10-129840261-G-A			Likely benign (Jul 26, 2018)
10-129840267-G-A		EBF3-related disorder	Benign (Dec 31, 2019)
10-129840294-T-TTGGGGCCTCG			Uncertain significance (Nov 06, 2023)
10-129840307-AC-A			Pathogenic (Dec 06, 2017)
10-129840309-G-A			Benign/Likely benign (Jul 01, 2024)
10-129840312-C-T			Likely benign (Jun 01, 2024)
10-129840320-C-T			Uncertain significance (Jan 04, 2024)
10-129840339-G-A		EBF3-related disorder	Likely benign (Jul 12, 2019)
10-129840398-GGAGGGTGACCGAA-G		Autism spectrum disorder	Uncertain significance (Aug 08, 2022)
10-129840860-A-G			Likely benign (Jul 01, 2024)
10-129840897-A-C			Uncertain significance (Mar 01, 2024)
10-129840944-GCTGA-G		EBF3-related disorder	Uncertain significance (Oct 25, 2022)
10-129840949-CTG-C		Hypotonia, ataxia, and delayed development syndrome	Likely pathogenic (Apr 09, 2020)
10-129840963-GACTGCTGGGGAGT-G		Hypotonia, ataxia, and delayed development syndrome • Inborn genetic diseases	Pathogenic (Aug 29, 2024)
10-129840969-T-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
10-129840970-G-A		Hypotonia, ataxia, and delayed development syndrome	Pathogenic (Jan 05, 2021)
10-129840997-G-A		Intellectual disability • Hypotonia, ataxia, and delayed development syndrome	Conflicting classifications of pathogenicity (Apr 04, 2022)
10-129841014-G-A			Uncertain significance (Apr 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EBF3	protein_coding	protein_coding	ENST00000368648	16	128559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000667	125543	0	1	125544	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.61	163	354	0.460	0.0000210	3612
Missense in Polyphen		38	96.714	0.39291		950
Synonymous	0.500	146	154	0.949	0.0000111	1061
Loss of Function	5.05	1	31.7	0.0316	0.00000166	342

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000881
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator (PubMed:28017373, PubMed:28017372, PubMed:28017370). Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3' (By similarity). {ECO:0000250|UniProtKB:Q07802, ECO:0000269|PubMed:28017370, ECO:0000269|PubMed:28017372, ECO:0000269|PubMed:28017373}.
• Pathway: Differentiation of white and brown adipocyte (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.0389
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.44

Haploinsufficiency Scores

• pHI: 0.136
• hipred: Y
• hipred_score: 0.773
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ebf3
• Phenotype: 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); 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)

Gene ontology

• Biological process: multicellular organism development;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;metal ion binding;protein dimerization activity