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 (Strong), mode of inheritance: AR
Roberts-SC phocomelia syndrome (Definitive), 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 (537 variants)
Roberts-SC_phocomelia_syndrome (229 variants)
Juberg-Hayward_syndrome (105 variants)
Inborn_genetic_diseases (59 variants)
ESCO2-related_disorder (20 variants)
not_specified (15 variants)
Hereditary_breast_ovarian_cancer_syndrome (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. These statistics are base on transcript: NM_001017420.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	204 clinvar	1 clinvar	213
missense	2 clinvar	3 clinvar	170 clinvar	15 clinvar	2 clinvar	192
nonsense	27 clinvar	3 clinvar				30
start loss		1				1
frameshift	57 clinvar	30 clinvar	1 clinvar			88
splice donor/acceptor (+/-2bp)	7 clinvar	19 clinvar	2 clinvar			28
Total	93	56	181	219	3

Highest pathogenic variant AF is 0.00008268884

Loading clinvar variants...

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