SEMA3E

semaphorin 3E, the group of Immunoglobulin like domain containing|Semaphorins

Basic information

Region (hg38): 7:83363237-83649139

Previous symbols: [ "SEMAH" ]

Links

ENSG00000170381 ∙ NCBI:9723 ∙ OMIM:608166 ∙ HGNC:10727 ∙ Uniprot:O15041 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CHARGE syndrome (Limited), mode of inheritance: AD
• Kallmann syndrome (Limited), mode of inheritance: AD
• CHARGE syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CHARGE syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	11241468; 15235037

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEMA3E gene.

• CHARGE association (424 variants)
• not provided (183 variants)
• SEMA3E-related condition (32 variants)
• CHARGE association;Hypogonadotropic hypogonadism 7 with or without anosmia (31 variants)
• Inborn genetic diseases (28 variants)
• Hypogonadotropic hypogonadism 7 with or without anosmia;CHARGE association (23 variants)
• not specified (9 variants)
• Amenorrhea (1 variants)
• Hypogonadotropic hypogonadism 7 with or without anosmia (1 variants)
• Isolated anophthalmia-microphthalmia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEMA3E 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			3	96	5	104
missense			234	6	2	242
nonsense			6			6
start loss						0
frameshift		1	4			5
inframe indel						0
splice donor/acceptor (+/-2bp)			3			3
splice region			13	20	1	34
non coding			1	86	92	179
Total	0	1	251	188	99

Variants in SEMA3E

This is a list of pathogenic ClinVar variants found in the SEMA3E region.

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

Position	Type	Phenotype	Significance	ClinVar
7-83367330-A-G			Benign (Sep 22, 2018)
7-83367359-A-G			Likely benign (May 26, 2019)
7-83367390-A-T			Benign (Aug 09, 2018)
7-83367515-A-T			Benign (Oct 05, 2018)
7-83367517-G-GATTT			Benign (Sep 22, 2018)
7-83367540-T-G			Benign (Sep 22, 2018)
7-83367594-C-A		CHARGE syndrome	Uncertain significance (Jul 03, 2023)
7-83367598-C-T		CHARGE syndrome	Likely benign (Sep 25, 2020)
7-83367599-G-A		CHARGE syndrome	Uncertain significance (Oct 08, 2023)
7-83367607-G-A		CHARGE syndrome	Likely benign (Jun 18, 2020)
7-83367610-C-CA		CHARGE syndrome	Uncertain significance (Feb 11, 2020)
7-83367612-G-A		CHARGE syndrome	Likely benign (Apr 08, 2020)
7-83367614-C-A		CHARGE syndrome	Uncertain significance (Apr 29, 2023)
7-83367631-G-A		CHARGE syndrome	Benign/Likely benign (Jan 28, 2024)
7-83367632-G-C		CHARGE syndrome	Uncertain significance (Mar 21, 2023)
7-83367635-C-T		CHARGE syndrome • Hypogonadotropic hypogonadism 7 with or without anosmia;CHARGE syndrome	Uncertain significance (Nov 07, 2023)
7-83367661-A-G		CHARGE syndrome	Likely benign (Oct 15, 2023)
7-83367675-A-T		CHARGE syndrome	Uncertain significance (Apr 29, 2022)
7-83367680-G-A		CHARGE syndrome	Uncertain significance (Apr 25, 2021)
7-83367690-G-T		CHARGE syndrome	Uncertain significance (Mar 14, 2023)
7-83367691-C-T		SEMA3E-related disorder	Likely benign (Jun 07, 2022)
7-83367694-T-C		CHARGE syndrome • SEMA3E-related disorder	Conflicting classifications of pathogenicity (Nov 19, 2023)
7-83367698-C-T		CHARGE syndrome	Uncertain significance (Jan 14, 2024)
7-83367698-CTCTT-C		CHARGE syndrome	Uncertain significance (Nov 01, 2022)
7-83367703-T-C		CHARGE syndrome	Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEMA3E	protein_coding	protein_coding	ENST00000307792	17	285105

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.71e-9	1.00	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.465	408	435	0.937	0.0000235	5096
Missense in Polyphen		137	172.08	0.79612		2018
Synonymous	-2.28	189	153	1.23	0.00000844	1426
Loss of Function	3.27	21	44.5	0.472	0.00000252	519

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in signaling via the cell surface receptor PLXND1. Mediates reorganization of the actin cytoskeleton, leading to the retraction of cell projections. Promotes focal adhesion disassembly and inhibits adhesion of endothelial cells to the extracellular matrix. Regulates angiogenesis, both during embryogenesis and after birth. Can down- regulate sprouting angiogenesis. Required for normal vascular patterning during embryogenesis. Plays an important role in ensuring the specificity of synapse formation (By similarity). {ECO:0000250}.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Other semaphorin interactions;Semaphorin interactions;Plexin-D1 Signaling;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.718
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.49

Haploinsufficiency Scores

• pHI: 0.0926
• hipred: Y
• hipred_score: 0.638
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.158

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sema3e
• Phenotype: embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye 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)

Zebrafish Information Network

• Gene name: sema3e
• Affected structure: axial vasculature
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: branching involved in blood vessel morphogenesis;neural crest cell migration;negative regulation of cell-matrix adhesion;sprouting angiogenesis;regulation of cell shape;negative regulation of angiogenesis;positive regulation of cell migration;negative regulation of axon extension involved in axon guidance;synapse organization;negative chemotaxis;semaphorin-plexin signaling pathway;regulation of actin cytoskeleton reorganization
• Cellular component: extracellular region;extracellular space;integral component of plasma membrane
• Molecular function: protein binding;semaphorin receptor binding;neuropilin binding;chemorepellent activity