EFNB1

ephrin B1, the group of Ephrins

Basic information

Region (hg38): X:68829021-68842160

Previous symbols: [ "EPLG2", "CFNS" ]

Links

ENSG00000090776 ∙ NCBI:1947 ∙ OMIM:300035 ∙ HGNC:3226 ∙ Uniprot:P98172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniofrontonasal syndrome (Supportive), mode of inheritance: XL
• craniofrontonasal syndrome (Definitive), mode of inheritance: XL
• craniofrontonasal syndrome (Strong), mode of inheritance: XL
• craniofrontonasal syndrome (Strong), mode of inheritance: XL
• craniofrontonasal syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniofrontonasal dysplasia	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	Craniofacial; Musculoskeletal	15166289; 15124102; 15959873; 16639408; 17941886; 18627045; 20734337; 21385071; 23509643

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EFNB1 gene.

• not provided (21 variants)
• Craniofrontonasal syndrome (15 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 EFNB1 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				15	2	17
missense	6	9	53	4	2	74
nonsense	10	3				13
start loss						0
frameshift	12	4	2			18
inframe indel	1					1
splice donor/acceptor (+/-2bp)	3	4				7
splice region			2	1		3
non coding				5	4	9
Total	32	20	55	24	8

Variants in EFNB1

This is a list of pathogenic ClinVar variants found in the EFNB1 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-68829082-C-T			Likely benign (Dec 12, 2020)
X-68829189-C-A			Likely benign (Apr 18, 2021)
X-68829392-G-T			Benign (Mar 16, 2019)
X-68829498-C-G			Likely benign (Nov 13, 2019)
X-68829771-G-A		EFNB1-related disorder	Likely benign (Mar 05, 2019)
X-68829777-A-G			Pathogenic (May 02, 2024)
X-68829783-C-T		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
X-68829786-C-T		Inborn genetic diseases	Uncertain significance (Apr 29, 2024)
X-68829794-G-A		EFNB1-related disorder	Likely benign (Jan 26, 2024)
X-68829800-G-A		Craniofrontonasal syndrome	Likely pathogenic (May 20, 2020)
X-68829806-C-T			Pathogenic (Aug 19, 2024)
X-68829811-G-A		EFNB1-related disorder	Likely pathogenic (Jul 19, 2023)
X-68829841-GC-G		Craniofrontonasal syndrome	Likely pathogenic (-)
X-68829848-C-T			Likely benign (Dec 19, 2023)
X-68829859-T-TG			Pathogenic (May 26, 2016)
X-68829868-ACCTGGAGCCCGTAT-A		Craniofrontonasal syndrome	Pathogenic (May 02, 2023)
X-68829868-A-ACCTGGAGCCCGTAT			Pathogenic (Jan 30, 2015)
X-68829876-C-G			Uncertain significance (Jun 26, 2024)
X-68829885-T-G		Craniofrontonasal syndrome	Pathogenic (Jun 01, 2006)
X-68829886-G-A		Craniofrontonasal syndrome	Pathogenic (Oct 09, 2024)
X-68829887-G-A		Craniofrontonasal syndrome	Pathogenic (May 20, 2021)
X-68829905-G-C		Craniofrontonasal syndrome	Likely pathogenic (Jan 03, 2024)
X-68829906-T-A		Craniofrontonasal syndrome	Pathogenic (Oct 28, 2016)
X-68829909-G-A		Craniofrontonasal syndrome	Conflicting classifications of pathogenicity (Apr 30, 2023)
X-68829913-C-T			Likely benign (Nov 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EFNB1	protein_coding	protein_coding	ENST00000204961	5	13151

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.933	0.0672	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	100	156	0.641	0.0000132	2241
Missense in Polyphen		31	64.037	0.4841		934
Synonymous	0.263	65	67.8	0.959	0.00000584	712
Loss of Function	2.71	0	8.58	0.00	6.16e-7	148

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: Binds to the receptor tyrosine kinases EPHB1 and EPHA1. Binds to, and induce the collapse of, commissural axons/growth cones in vitro. May play a role in constraining the orientation of longitudinally projecting axons (By similarity). {ECO:0000250}.
• Disease: DISEASE: Craniofrontonasal syndrome (CFNS) [MIM:304110]: X-linked inherited syndrome characterized by hypertelorism, coronal synostosis with brachycephaly, downslanting palpebral fissures, clefting of the nasal tip, joint anomalies, longitudinally grooved fingernails and other digital anomalies. {ECO:0000269|PubMed:15124102, ECO:0000269|PubMed:15166289, ECO:0000269|PubMed:15959873}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;EPH-Ephrin signaling;Ephrin signaling;Ephrin B reverse signaling;Axon guidance;EPHB forward signaling (Consensus)

Recessive Scores

• pRec: 0.371

Intolerance Scores

• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

• pHI: 0.268
• hipred: Y
• hipred_score: 0.645
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.862

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Efnb1
• Phenotype: 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; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; vision/eye phenotype; craniofacial 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); hematopoietic system phenotype; embryo phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; hearing/vestibular/ear 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); limbs/digits/tail phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: efnb1
• Affected structure: hepatoblast
• Phenotype tag: abnormal
• Phenotype quality: anterior orientation

Gene ontology

• Biological process: neural crest cell migration;cell adhesion;cell-cell signaling;axon guidance;embryonic pattern specification;peptidyl-tyrosine phosphorylation;T cell costimulation;positive regulation of T cell proliferation;ephrin receptor signaling pathway
• Cellular component: nucleus;cytoplasm;plasma membrane;integral component of plasma membrane;membrane raft;synapse;extracellular exosome
• Molecular function: protein tyrosine kinase activity;protein binding;ephrin receptor binding