ESCO2

establishment of sister chromatid cohesion N-acetyltransferase 2, the group of Lysine acetyltransferases

Basic information

Region (hg38): 8:27771949-27812640

Previous symbols: [ "RBS" ]

Links

ENSG00000171320 ∙ NCBI:157570 ∙ OMIM:609353 ∙ HGNC:27230 ∙ Uniprot:Q56NI9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Roberts-SC phocomelia syndrome (Definitive), mode of inheritance: AR
• Roberts syndrome (Strong), mode of inheritance: AR
• Roberts syndrome (Supportive), mode of inheritance: AR
• Roberts-SC phocomelia syndrome (Definitive), mode of inheritance: AR
• Roberts-SC phocomelia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Roberts-SC phocomelia syndrome; Juberg-Hayward syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	7067161; 3740099; 1642282; 16380922; 15821733; 18411254; 19574259; 32255174; 32977150

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ESCO2 gene.

• not provided (90 variants)
• Roberts-SC phocomelia syndrome (21 variants)
• Roberts syndrome (6 variants)
• Roberts-SC phocomelia syndrome;Juberg-Hayward syndrome (2 variants)
• ESCO2-related disorder (2 variants)
• Juberg-Hayward syndrome;Roberts-SC phocomelia syndrome (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ESCO2 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				191	1	192
missense		2	87	7	3	99
nonsense	26	2				28
start loss						0
frameshift	60	5				65
inframe indel			4			4
splice donor/acceptor (+/-2bp)	7	18				25
splice region			4	37	2	43
non coding			31	85	35	151
Total	93	27	122	283	39

Highest pathogenic variant AF is 0.0000591

Variants in ESCO2

This is a list of pathogenic ClinVar variants found in the ESCO2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-27774556-T-G		Roberts-SC phocomelia syndrome	Benign (Jan 13, 2018)
8-27774580-G-A		Roberts-SC phocomelia syndrome	Uncertain significance (Jan 13, 2018)
8-27774586-C-G		Roberts-SC phocomelia syndrome	Uncertain significance (Jan 12, 2018)
8-27774591-C-T		Roberts-SC phocomelia syndrome	Uncertain significance (Jan 13, 2018)
8-27774622-A-T		Roberts-SC phocomelia syndrome	Uncertain significance (Jan 13, 2018)
8-27774626-C-T		not specified	Benign (Apr 04, 2017)
8-27775312-C-T			Benign (Jul 07, 2018)
8-27775350-T-G			Benign (Jul 07, 2018)
8-27775529-T-A			Likely benign (Jan 23, 2023)
8-27775532-A-G			Likely benign (Dec 09, 2023)
8-27775533-AG-A			Pathogenic (Mar 04, 2023)
8-27775535-G-A			Likely benign (May 30, 2023)
8-27775537-A-C			Uncertain significance (Jul 07, 2022)
8-27775540-G-A		ESCO2-related disorder	Uncertain significance (Oct 20, 2023)
8-27775541-G-A			Likely benign (Sep 23, 2022)
8-27775544-G-A			Likely benign (Jun 10, 2022)
8-27775552-C-A			Uncertain significance (Apr 11, 2022)
8-27775555-T-A			Pathogenic (Oct 04, 2022)
8-27775564-A-G		Inborn genetic diseases	Uncertain significance (Oct 29, 2022)
8-27775565-C-T			Likely benign (Jul 16, 2023)
8-27775575-T-G		Roberts-SC phocomelia syndrome	Uncertain significance (Jan 13, 2018)
8-27775576-C-A			Likely benign (May 25, 2022)
8-27775576-C-G			Likely benign (Jan 21, 2023)
8-27775587-T-A			Likely benign (Dec 01, 2023)
8-27775720-G-A			Benign (Dec 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ESCO2	protein_coding	protein_coding	ENST00000305188	10	40692

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.16e-7	0.985	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.408	281	301	0.934	0.0000146	3980
Missense in Polyphen		70	90.575	0.77284		1170
Synonymous	0.561	101	108	0.931	0.00000535	1106
Loss of Function	2.24	15	27.7	0.541	0.00000143	363

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000220	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000220	0.000217
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acetyltransferase required for the establishment of sister chromatid cohesion (PubMed:15821733, PubMed:15958495). Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during the S phase. Acetylates the cohesin component SMC3 (PubMed:21111234). {ECO:0000269|PubMed:15821733, ECO:0000269|PubMed:15958495, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234}.
• Disease: DISEASE: Roberts syndrome (RBS) [MIM:268300]: Rare autosomal recessive disorder characterized by pre- and postnatal growth retardation, microcephaly, bilateral cleft lip and palate, and mesomelic symmetric limb reduction. Severely affected infants may be stillborn or die shortly after birth. RBS chromosomes have a lack of cohesion involving the heterochromatic C-banding regions around centromeres and the distal portion of the long arm of the Y chromosome (known as premature centromere separation, heterochromatin repulsion or puffing, or RS effect). {ECO:0000269|PubMed:15821733}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: SC phocomelia syndrome (SCPS) [MIM:269000]: Has a milder phenotype than RBS, with a lesser degree of symmetric limb reduction and additionally includes flexion contractures of various joints, midfacial hemangioma, hypoplastic cartilage of ears and nose, scant silvery-blond hair, and cloudy corneae. Although microcephaly is present, mental retardation may be mild and survival into adulthood is common. {ECO:0000269|PubMed:16380922}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Establishment of Sister Chromatid Cohesion;S Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.208

Intolerance Scores

• loftool: 0.601
• rvis_EVS: 0.73
• rvis_percentile_EVS: 86.27

Haploinsufficiency Scores

• pHI: 0.0690
• hipred: Y
• hipred_score: 0.658
• ghis: 0.419

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Esco2
• 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); embryo phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: esco2
• Affected structure: cell
• Phenotype tag: abnormal
• Phenotype quality: deformed

Gene ontology

• Biological process: hematopoietic progenitor cell differentiation;regulation of DNA replication;double-strand break repair;sister chromatid cohesion;post-translational protein acetylation;protein localization to chromatin
• Cellular component: chromatin;XY body;nucleus;nucleoplasm;chromosome;Golgi apparatus;chromocenter;cell junction;nuclear pericentric heterochromatin;site of double-strand break
• Molecular function: lysine N-acetyltransferase activity, acting on acetyl phosphate as donor;N-acetyltransferase activity;acetyltransferase activity;metal ion binding