ERF

ETS2 repressor factor, the group of ETS transcription factor family

Basic information

Region (hg38): 19:42247569-42255128

Links

ENSG00000105722 ∙ NCBI:2077 ∙ OMIM:611888 ∙ HGNC:3444 ∙ Uniprot:P50548 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniosynostosis 4 (Strong), mode of inheritance: AD
• craniosynostosis 4 (Strong), mode of inheritance: AD
• Chitayat syndrome (Moderate), mode of inheritance: AD
• craniosynostosis 4 (Moderate), mode of inheritance: AD
• Crouzon syndrome (Supportive), mode of inheritance: AD
• isolated scaphocephaly (Supportive), mode of inheritance: AD
• craniosynostosis 4 (Strong), mode of inheritance: AD
• craniosynostosis 4 (Definitive), mode of inheritance: AD
• Chitayat syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chitayat syndrome	AD	Pulmonary	Among other features, Chitayat syndrome can include neonatal respiratory distress requiring ventilatory support, and awareness may allow early recognition and management	Craniofacial; Musculoskeletal; Neurologic; Pulmonary	8418638; 23354439; 26097063; 27738187

ClinVar

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

• TWIST1-related craniosynostosis (13 variants)
• Inborn genetic diseases (5 variants)
• not provided (4 variants)
• Craniosynostosis 4 (4 variants)
• ERF-related disorder (1 variants)
• Craniosynostosis 4;Chitayat syndrome (1 variants)
• Chitayat syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERF 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				32	9	41
missense	2	3	72	11	2	90
nonsense	7	5	1			13
start loss	1					1
frameshift	7	9	3			19
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)	1					1
splice region			1	1	1	3
non coding			1	3	2	6
Total	18	17	80	47	13

Highest pathogenic variant AF is 0.0000136

Variants in ERF

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

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

Position	Type	Phenotype	Significance	ClinVar
19-42248469-G-A			Uncertain significance (Jul 07, 2022)
19-42248475-C-T		Inborn genetic diseases	Uncertain significance (Jun 22, 2024)
19-42248476-G-A		11 conditions • Inborn genetic diseases	Uncertain significance (Oct 30, 2020)
19-42248498-C-T		TWIST1-related craniosynostosis • ERF-related disorder	Benign (Aug 02, 2023)
19-42248499-G-A			Uncertain significance (Mar 09, 2023)
19-42248510-G-A		TWIST1-related craniosynostosis	Likely benign (Nov 14, 2022)
19-42248526-C-G		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
19-42248542-GC-G			Uncertain significance (Mar 11, 2024)
19-42248547-C-G		Inborn genetic diseases	Uncertain significance (Apr 20, 2023)
19-42248550-G-C		Inborn genetic diseases	Uncertain significance (Jun 21, 2021)
19-42248560-GC-G		Noonan syndrome	Uncertain significance (-)
19-42248576-C-G		Inborn genetic diseases	Uncertain significance (Dec 27, 2022)
19-42248577-T-C		ERF-related disorder	Uncertain significance (Oct 31, 2023)
19-42248585-C-G			Benign (Oct 17, 2017)
19-42248602-AG-A		Noonan Syndrome-like developmental disorder	Pathogenic (Dec 31, 2023)
19-42248611-CG-C		TWIST1-related craniosynostosis	Uncertain significance (Nov 03, 2022)
19-42248634-C-T		TWIST1-related craniosynostosis • Inborn genetic diseases	Uncertain significance (Jun 21, 2023)
19-42248651-G-A		TWIST1-related craniosynostosis	Likely benign (Sep 19, 2022)
19-42248668-G-A			Likely benign (Feb 01, 2023)
19-42248669-C-G			Uncertain significance (Dec 04, 2023)
19-42248670-T-C			Uncertain significance (Aug 01, 2022)
19-42248671-T-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
19-42248680-T-C			Uncertain significance (Dec 18, 2022)
19-42248695-C-T			Uncertain significance (Jan 31, 2023)
19-42248698-G-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERF	protein_coding	protein_coding	ENST00000222329	4	7586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0103	125719	0	4	125723	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	238	358	0.665	0.0000242	3427
Missense in Polyphen		49	110.47	0.44354		1066
Synonymous	-1.84	199	169	1.18	0.0000120	1236
Loss of Function	3.73	1	18.2	0.0551	0.00000101	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000281	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potent transcriptional repressor that binds to the H1 element of the Ets2 promoter. May regulate other genes involved in cellular proliferation. Required for extraembryonic ectoderm differentiation, ectoplacental cone cavity closure, and chorioallantoic attachment (By similarity). May be important for regulating trophoblast stem cell differentiation (By similarity). {ECO:0000250}.
• Disease: DISEASE: Craniosynostosis 4 (CRS4) [MIM:600775]: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. {ECO:0000269|PubMed:23354439}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Chitayat syndrome (CHYTS) [MIM:617180]: An autosomal dominant syndrome characterized by hyperphalangism, partial syndactyly, bilateral accessory phalanx resulting in shortened index fingers, hallux valgus, brachydactyly, facial anomalies, diffuse bronchomalacia, and respiratory distress at birth and in infancy. {ECO:0000269|PubMed:27738187}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Oncogene Induced Senescence;Cellular Senescence;Cellular responses to stress;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.0200
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.638
• hipred: Y
• hipred_score: 0.785
• ghis: 0.585

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Erf
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; embryo 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); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system 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); skeleton phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;mitotic cell cycle;regulation of transcription by RNA polymerase II;cell differentiation
• Cellular component: nucleus;nucleoplasm;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;transcription corepressor activity;sequence-specific DNA binding