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SEMA3A

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

Basic information

Region (hg38): 7:83955776-84492724

Previous symbols: [ "SEMAD" ]

Links

ENSG00000075213NCBI:10371OMIM:603961HGNC:10723Uniprot:Q14563AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Kallmann syndrome (Supportive), mode of inheritance: AD
  • Brugada syndrome (Supportive), mode of inheritance: AD
  • hypogonadotropic hypogonadism 16 with or without anosmia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypogonadotropic hypogonadism 16 with or without anosmiaADEndocrineSurveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be requiredEndocrine; Genitourinary; Neurologic22416012
Surveillance in adolescence related to sexual maturation is indicated, and in order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEMA3A gene.

  • not provided (128 variants)
  • SEMA3A-related condition (24 variants)
  • Inborn genetic diseases (18 variants)
  • not specified (7 variants)
  • Hypogonadotropic hypogonadism 16 with or without anosmia (7 variants)
  • Martsolf syndrome 1 (1 variants)
  • Delayed puberty (1 variants)
  • Amenorrhea (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 SEMA3A 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
20
clinvar
5
clinvar
25
missense
53
clinvar
6
clinvar
1
clinvar
60
nonsense
1
clinvar
1
clinvar
2
start loss
0
frameshift
0
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
splice region
1
2
3
6
non coding
12
clinvar
47
clinvar
59
Total 0 1 55 38 53

Variants in SEMA3A

This is a list of pathogenic ClinVar variants found in the SEMA3A region.

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

Position Type Phenotype Significance ClinVar
7-83961370-C-T SEMA3A-related condition Likely benign (Apr 19, 2022)3061718
7-83961401-G-A SEMA3A-related condition Likely benign (Jan 13, 2023)3029529
7-83961420-C-T SEMA3A-related condition Uncertain significance (Dec 18, 2023)3056586
7-83961430-T-G Uncertain significance (Sep 06, 2022)1941145
7-83961449-T-C Likely benign (Jun 06, 2018)748650
7-83961457-T-C Inborn genetic diseases • SEMA3A-related condition Uncertain significance (Jun 20, 2023)2550283
7-83961487-G-A SEMA3A-related condition Uncertain significance (Jan 02, 2024)2136550
7-83961489-C-T Hypogonadotropic hypogonadism 16 with or without anosmia • SEMA3A-related condition Uncertain significance (Dec 31, 2023)68835
7-83961498-C-T Martsolf syndrome 1 Uncertain significance (Apr 01, 2022)68834
7-83961527-C-T SEMA3A-related condition Likely benign (Dec 16, 2021)743998
7-83961536-T-C not specified Benign (Jan 31, 2024)194754
7-83961536-TG-CA SEMA3A-related condition Conflicting classifications of pathogenicity (Aug 10, 2023)2174235
7-83961537-G-A Delayed puberty • SEMA3A-related condition Conflicting classifications of pathogenicity (Feb 23, 2022)180149
7-83961547-T-G Inborn genetic diseases Uncertain significance (Aug 28, 2023)2599485
7-83961555-T-C Inborn genetic diseases Uncertain significance (Feb 28, 2023)2490901
7-83961606-C-T Inborn genetic diseases Uncertain significance (Jan 19, 2022)2272271
7-83961625-T-C Hypogonadotropic hypogonadism 16 with or without anosmia • SEMA3A-related condition Uncertain significance (Feb 21, 2024)68833
7-83961641-A-G Likely benign (Apr 07, 2018)739349
7-83961657-A-T Uncertain significance (Aug 17, 2023)2753578
7-83961667-C-T Uncertain significance (Nov 01, 2022)1966826
7-83961683-A-AATG SEMA3A-related condition Uncertain significance (Apr 11, 2023)2634572
7-83961727-G-A Inborn genetic diseases Uncertain significance (Jun 02, 2023)1312630
7-83961733-C-T Inborn genetic diseases • SEMA3A-related condition Conflicting classifications of pathogenicity (Feb 05, 2024)2589600
7-83961734-C-T not specified • SEMA3A-related condition Benign/Likely benign (Apr 10, 2023)719714
7-83961735-G-T Uncertain significance (Jul 17, 2023)2089876

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SEMA3Aprotein_codingprotein_codingENST00000265362 17536948
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9780.02211257320151257470.0000596
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.753274290.7620.00002255118
Missense in Polyphen120187.720.639242215
Synonymous0.5101431510.9470.000008101400
Loss of Function5.27847.00.1700.00000287499

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001240.000123
Ashkenazi Jewish0.000.00
East Asian0.0001140.000109
Finnish0.000.00
European (Non-Finnish)0.00008880.0000879
Middle Eastern0.0001140.000109
South Asian0.00003290.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Involved in the development of the olfactory system and in neuronal control of puberty. Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Binds to the complex neuropilin-1/plexin-1. {ECO:0000269|PubMed:22416012}.;
Disease
DISEASE: Hypogonadotropic hypogonadism 16 with or without anosmia (HH16) [MIM:614897]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:22416012, ECO:0000269|PubMed:22927827, ECO:0000269|PubMed:25077900}. Note=The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry.;
Pathway
Axon guidance - Homo sapiens (human);Angiogenesis overview;Olfactory bulb development and olfactory learning;Developmental Biology;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;Sema3A PAK dependent Axon repulsion;Semaphorin interactions;Axon guidance;CRMPs in Sema3A signaling (Consensus)

Recessive Scores

pRec
0.414

Intolerance Scores

loftool
0.477
rvis_EVS
0.34
rvis_percentile_EVS
73.68

Haploinsufficiency Scores

pHI
0.848
hipred
Y
hipred_score
0.704
ghis
0.453

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.473

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sema3a
Phenotype
hematopoietic system 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton 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); growth/size/body region phenotype; cellular phenotype;

Zebrafish Information Network

Gene name
sema3ab
Affected structure
intersegmental vessel
Phenotype tag
abnormal
Phenotype quality
morphology

Gene ontology

Biological process
neural crest cell migration;neuron migration;regulation of heart rate;apoptotic process;axon guidance;axonal fasciculation;negative regulation of epithelial cell migration;negative regulation of neuron projection development;facial nerve structural organization;trigeminal nerve structural organization;nerve development;olfactory bulb development;branchiomotor neuron axon guidance;gonadotrophin-releasing hormone neuronal migration to the hypothalamus;positive regulation of cell migration;ventral trunk neural crest cell migration;positive regulation of JNK cascade;sympathetic nervous system development;regulation of axon extension involved in axon guidance;negative regulation of axon extension involved in axon guidance;axon extension involved in axon guidance;sensory system development;negative chemotaxis;axonogenesis involved in innervation;dichotomous subdivision of terminal units involved in salivary gland branching;sympathetic ganglion development;trigeminal ganglion development;semaphorin-plexin signaling pathway;sympathetic neuron projection extension;sympathetic neuron projection guidance;basal dendrite arborization;neural crest cell migration involved in autonomic nervous system development;semaphorin-plexin signaling pathway involved in neuron projection guidance;semaphorin-plexin signaling pathway involved in axon guidance;neural crest cell migration involved in sympathetic nervous system development;facioacoustic ganglion development;positive regulation of male gonad development;positive regulation of neuron migration
Cellular component
extracellular region;extracellular space;integral component of plasma membrane;axon;dendrite
Molecular function
semaphorin receptor binding;neuropilin binding;chemorepellent activity