EBP

EBP cholestenol delta-isomerase

Basic information

Region (hg38): X:48521798-48528716

Previous symbols: [ "CDPX2" ]

Links

ENSG00000147155 ∙ NCBI:10682 ∙ OMIM:300205 ∙ HGNC:3133 ∙ Uniprot:Q15125 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chondrodysplasia punctata 2, X-linked dominant (Definitive), mode of inheritance: XLD
• MEND syndrome (Moderate), mode of inheritance: XL
• chondrodysplasia punctata 2, X-linked dominant (Definitive), mode of inheritance: XL
• X-linked chondrodysplasia punctata 2 (Supportive), mode of inheritance: XL
• MEND syndrome (Supportive), mode of inheritance: XL
• X-linked chondrodysplasia punctata 2 (Definitive), mode of inheritance: XL
• MEND syndrome (Definitive), mode of inheritance: XL
• X-linked chondrodysplasia punctata 2 (Strong), mode of inheritance: XL
• MEND syndrome (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chondrodysplasia punctata 2, X-linked dominant; Male EBP disorder with neurologic defects (MEND syndrome)	XL	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	Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	830452; 535904; 10391219; 10391218; 11038443; 12503101; 12509714; 18573709; 21634086; 22121851; 22229330; 23307567; 24700572

ClinVar

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

• not provided (100 variants)
• Chondrodysplasia punctata 2 X-linked dominant (44 variants)
• not specified (12 variants)
• Inborn genetic diseases (5 variants)
• MEND syndrome (5 variants)
• Connective tissue disorder (4 variants)
• Chondrodysplasia punctata 2 X-linked dominant;MEND syndrome (3 variants)
• MEND syndrome;Chondrodysplasia punctata 2 X-linked dominant (1 variants)
• EBP-related condition (1 variants)
• Developmental disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EBP 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			1	13	4	18
missense	4	22	23	6	1	56
nonsense	14					14
start loss						0
frameshift	9		1			10
inframe indel		3	2			5
splice donor/acceptor (+/-2bp)	3	2				5
splice region		1	3	4		8
non coding				10	8	18
Total	30	27	27	29	13

Variants in EBP

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

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

Position	Type	Phenotype	Significance	ClinVar
X-48521910-G-C		not specified • Connective tissue disorder	Benign/Likely benign (Nov 19, 2020)
X-48523553-G-A			Likely benign (Aug 15, 2019)
X-48523553-GA-G			Likely benign (Jul 16, 2020)
X-48523553-G-GA			Benign (Oct 06, 2019)
X-48523711-CT-C			Benign (Jun 04, 2018)
X-48523711-C-CT			Benign (May 09, 2020)
X-48523711-C-CTT			Benign (Aug 23, 2019)
X-48523711-C-CTTTTT			Likely benign (Dec 13, 2019)
X-48523723-T-C		not specified	Likely benign (Aug 31, 2016)
X-48523730-A-T			Likely benign (Jul 09, 2018)
X-48523753-G-A		not specified	Likely benign (Apr 22, 2016)
X-48523782-A-G			Uncertain significance (Jul 09, 2022)
X-48523784-G-A		not specified • Inborn genetic diseases • Chondrodysplasia punctata 2 X-linked dominant;MEND syndrome • EBP-related disorder	Benign/Likely benign (Jan 29, 2024)
X-48523786-G-A			Likely benign (Jun 13, 2022)
X-48523786-G-T		not specified • MEND syndrome • Chondrodysplasia punctata 2 X-linked dominant	Benign (Jan 31, 2024)
X-48523804-C-A		Chondrodysplasia punctata 2, X-linked dominant, atypical	Pathogenic (Jun 01, 2012)
X-48523807-G-A			Pathogenic (Nov 22, 2022)
X-48523809-C-G			Conflicting classifications of pathogenicity (Jan 01, 2023)
X-48523824-T-C		MEND syndrome	Pathogenic (Oct 15, 2003)
X-48523830-A-C		Connective tissue disorder	Conflicting classifications of pathogenicity (Jan 14, 2021)
X-48523837-A-G			Benign (Aug 24, 2023)
X-48523848-G-A			Uncertain significance (Jul 26, 2023)
X-48523858-G-A		Chondrodysplasia punctata 2 X-linked dominant	Pathogenic (Jul 01, 1999)
X-48523873-CCTCTT-C			Pathogenic (Jun 13, 2021)
X-48523887-C-T			Uncertain significance (Jun 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EBP	protein_coding	protein_coding	ENST00000495186	4	7559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.936	0.0633	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.49	55	96.3	0.571	0.00000789	1477
Missense in Polyphen		13	33.23	0.39121		558
Synonymous	0.0598	41	41.5	0.988	0.00000352	476
Loss of Function	2.74	0	8.75	0.00	7.03e-7	110

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers. {ECO:0000269|PubMed:12760743, ECO:0000269|PubMed:8798407, ECO:0000269|PubMed:9894009}.
• Disease: DISEASE: Chondrodysplasia punctata 2, X-linked dominant (CDPX2) [MIM:302960]: A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-8(9)- en-3-beta-ol in the plasma and tissues. {ECO:0000269|PubMed:10391218, ECO:0000269|PubMed:10391219, ECO:0000269|PubMed:10942423, ECO:0000269|PubMed:11493318, ECO:0000269|PubMed:18176751, ECO:0000269|PubMed:25814754}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: MEND syndrome (MEND) [MIM:300960]: An X-linked recessive disorder associated with a defect in sterol biosynthesis. Disease manifestations and severity are highly variable. Clinical features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. {ECO:0000269|PubMed:12503101, ECO:0000269|PubMed:20949533, ECO:0000269|PubMed:24459067, ECO:0000269|PubMed:24700572}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid biosynthesis - Homo sapiens (human);Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Metabolism of lipids;Squalene and cholesterol biosynthesis;Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;cholesterol biosynthesis I;Cholesterol biosynthesis via desmosterol;Cholesterol biosynthesis via lathosterol;Cholesterol biosynthesis (Consensus)

Recessive Scores

• pRec: 0.0987

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.254
• hipred: Y
• hipred_score: 0.531
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ebp
• Phenotype: embryo phenotype; hematopoietic system 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: skeletal system development;cholesterol biosynthetic process;drug transmembrane transport;cholesterol metabolic process;sterol biosynthetic process;hemopoiesis;cholesterol biosynthetic process via desmosterol;cholesterol biosynthetic process via lathosterol
• Cellular component: nuclear envelope;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of plasma membrane;cytoplasmic vesicle
• Molecular function: C-8 sterol isomerase activity;steroid delta-isomerase activity;transmembrane signaling receptor activity;protein binding;drug transmembrane transporter activity;cholestenol delta-isomerase activity