EPHB6

protein-coding

EPH receptor B6, the group of EPH receptors|Sterile alpha motif domain containing

Gene summary

This gene encodes a member of a family of transmembrane proteins that function as receptors for ephrin-B family proteins. Unlike other members of this family, the encoded protein does not contain a functional kinase domain. Activity of this protein can influence cell adhesion and migration. Expression of this gene is downregulated during tumor progression, suggesting that the protein may suppress tumor invasion and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

MANE transcript

NM_004445.6

Inheritance

—

ClinVar variants

U:156B:7

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr7:142,855,061-142,871,094

External References & Databases

Ensembl (ENSG00000106123)

Transcript & Mutation Effects

hg38 • Region Span ~16.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPHB6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 142

not providedTotal: 2

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004445.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar			4
missense			145 clinvar	7 clinvar		152
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	156	7	0	163

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004445.6	RefSeq	NP_004436.4	16	MANE Select
ENST00000652003.1	Ensembl	ENSP00000498670.1	16	MANE Select
NM_001280794.3	RefSeq	NP_001267723.2	14	Standard
NM_001280795.2	RefSeq	NP_001267724.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Developmental Biology
EPH-Ephrin signaling
Ephrin signaling
Axon guidance

Biological Process

transmembrane receptor protein tyrosine kinase signaling pathway
axon guidance
peptidyl-tyrosine phosphorylation
ephrin receptor signaling pathway

Molecular Function

protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
ephrin receptor activity
transmembrane-ephrin receptor activity
ATP binding

Cellular Component

extracellular region
cytosol
plasma membrane
integral component of plasma membrane
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392957
Coding exons: 16
Length: 16056
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125748
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.981	535	603	0.888	0.0000413	6520
Missense (PolyPhen)		207	256.76	0.80619		2816
Synonymous	-0.912	268	250	1.07	0.0000162	2207
Loss of Function	3.66	20	47.1	0.424	0.00000272	479

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Kinase-defective receptor for members of the ephrin-B family. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation with ephrin-B2. Inhibits JNK activation, T-cell receptor-induced IL-2 secretion and CD25 expression upon stimulation with ephrin-B2. {ECO:0000269|PubMed:12517763, ECO:0000269|PubMed:15955811}.;

Recessive Scores

pRec: 0.230

Intolerance Scores

LoFtool: 0.241
RVIS EVS: -1.43
RVIS percentile EVS: 4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.721

Gene Damage Prediction

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