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Symbol SEMA3A contributors: mct/shn/pgu - updated : 15-10-2015
HGNC name sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A
HGNC id 10723
Corresponding disease
HHI4 hypogonadism hypogonadotropic isolated 4
Location 7p21.11      Physical location : 83.587.664 - 83.824.217
Genatlas name
  • semaphorin III
  • semaphorin L
  • semaphorin-3A
  • Synonym name
  • sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A
  • semaphorin-3A
  • collapsin 1
  • semaphorin D
  • semaphorin D
  • semaphorin III
  • semaphorin L
  • sema III
  • Synonym symbol(s) SEMAL, MGC133243, SEMA1, SEMAD, SEMAIII, SemD, coll-1, sema III, SEMD, Hsema-I, Hsema-III,
    TYPE functioning gene
    STRUCTURE 236.56 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D7S2212 - D7S2540 - SEMA3A - D7S2845 - D7S2485 - qter
    Physical map
    LOC392066 7 similar to 60S ribosomal protein L10 (QM protein homolog) GNAI1 7q21.3-q22.1 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 LOC346562 CD36 7q11.2 CD36 antigen (collagen type I receptor, thrombospondin receptor) SEMA3C 7q21-q31 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C HGF 7q21.1 hepatocyte growth factor (hepatopoietin A; scatter factor) CACNA2D1 7q21.3-q22.1 calcium channel, voltage-dependent, alpha 2/delta subunit 1 PCLO 7q11.23-q21.3 piccolo (presynaptic cytomatrix protein) LOC389530 7 similar to [Segment 1 of 2] Piccolo protein (Aczonin) SEMA3E 7q21.11-q31.33 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3E SEMA3A 2q37-qter sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A HMG17P1 7q11-q21 high-mobility group (nonhistone chromosomal) protein 17 pseudogene 1 LOC285984 7q21.12 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) SEMA3D 7q21.12 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3D LOC392067 7 similar to dynein, cytoplasmic, light peptide GRM3 7q21.1-q21.2 glutamate receptor, metabotropic 3 FLJ31340 7q21.13 hypothetical protein FLJ31340 DMTF1 7q21.1 cyclin D binding myb-like transcription factor 1 C7orf23 7q21.1-q21.2 chromosome 7 open reading frame 23 TP53AP1 7q21.1 TP53 activated protein 1 CROT 7q21.1 carnitine O-octanoyltransferase ABCB4 7q21.1 ATP-binding cassette, sub-family B (MDR/TAP), member 4 ABCB1 7q21.1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 RPIB9 7q21.13 Rap2-binding protein 9 MCFP 7q21.13 mitochondrial carrier family protein ASK 7q21.3 mitochondrial carrier family protein ADAM22 7q21.1 a disintegrin and metalloproteinase domain 22
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 5672 - 771 - 2009 19480842
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     mouth   highly
    Nervousnervecranial nerve  highly
    Skeletonappendicular skeleton     Homo sapiens
    Visualeyeanterior segmentcornea highly
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast Homo sapiens
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion secreted
    at STAGE
    physiological period fetal
    Text fetal eyes
  • N terminal signal peptide
  • a SEMA domain containing about 14 cysteine residues,
  • a PSI domain
  • an Ig-like C2 type motif
  • a C terminal short basic domain
    interspecies ortholog to Sema3a, Mus musculus
    ortholog to Sema3a, Rattus norvegicus
    ortholog to SEMA3A, Pan troglodytes
  • semaphorin family
  • CATEGORY secretory , signaling growth factor
    basic FUNCTION
  • repellent of the nerve growth cone guidance
  • inducing the collapse and paralysis of neuronal growth cones
  • implicated in regulation of sensory innervation of the cornea
  • essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (
  • can function as potent anti-tumorigenic agents (but is required expression of appropriate semaphorin receptors by tumor cells)
  • could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism
  • one of the major inhibitors of axonal regeneration, and of other regenerative responses after spinal cord injury
  • neural chemorepellent, involved in cardiac sympathetic innervation patterning, important for the maintenance of arrhythmia-free hearts and playing a critical role for heart rate control
  • playing a crucial role for the cardiac sympathetic patterning, not only during embryonic development but also after birth
  • may function as a chemoattractive guidance signal for the radial migration of newborn cortical neurons toward upper layers
  • may help to establish the dopaminergic projection from the midbrain to the striatum during embryonic development
  • enhanced axon growth
  • plays a role in induction of apoptosis in monocyte-derived macrophages that are resistant to Fas-induced apoptosis, and its function can be modulated in inflammatory conditions
  • playing a role as an antiangiogenic factor in meningiomas with its decrease being associated with the development of recurrences
  • PLXNA4 and SEMA3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm
  • induces CACNA1E channel-dependent conversion of axons to dendrites)
  • SEMA3A-mediated signaling and axonal repulsion require VAMP2-dependent vesicular traffic
  • exerts an osteoprotective effect by both suppressing osteoclastic bone resorption and increasing osteoblastic bone formation
  • functions as a potent osteoprotective factor by synchronously inhibiting bone resorption and promoting bone formation
  • inhibits osteoclast differentiation and promotes osteoblastic bone formation, and is thus a potent osteoprotective factor produced by osteoblastic cells
  • secreted factor that navigates axons and dendrites of developing neurons, facilitates axonal transport
  • induces facilitation of axonal transport via local calcium signaling in growth cone
  • requires neuronal activity to promote dendritic complexity, presumably because silencing neurons leads to a proteasome-dependent reduction of PLXNA1 in dendrites
  • role of the PLXNA2 receptor in SEMA3A and SEMA3B signal transduction
  • SEMA3A, -3C, and -3F, likely with coreceptors NRP1, NRP2, and plexin-A1 and/or -A3, promote migration and possibly other activities of human DCs during innate and adaptive immune responses
    text vascular morphogenesis
    signaling signal transduction
    signaling pathway in oligodendroglia
    a component
  • complexing with NRP1 in the regulation of migration and adhesion of thymocytes
    small molecule
  • inhibiting integrin function
  • colocalizing with DYSPL2, DYSPL5
  • SEMA3A signaling pathway mediated by DYSPL2, DYSPL5
  • neuropilin-1, NRP1 and Collapsin-1 (
  • Plexin-neuropilin-1 complexes (
  • reversible inhibitor of oligodendrocyte precursor cell differentiation in vitro and has an important role in the differentiation block occurring in multiple sclerosis lesions(
  • SEMA3A and NRP1 binding stimulated osteoblast and inhibited adipocyte differentiation through the canonical WNT/CTNNB1 signalling pathway
  • initiates growth cone collapse via activation of calpain that in turn potentiates TRPC5 activity
  • SEMA3A and NRP1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons
  • SEMA3A elevates endothelial cell permeability through PPP2CA inactivation
  • CHN1 is critical in the pathfinding of oculomotor neurons as a downstream component of the SEMA3A/PLXNA repellent signaling pathway
  • SEMA3A signaling in ECs is linked with increased CIITA levels and higher HLA-DR expression, resulting in CD4+ T-cell activation
  • FARP1 is required by SEMA3A to promote dendritic arborization of hippocampal neurons, and SEMA3A regulates dendritic F-actin distribution via FARP1
  • cell & other
    inhibited by SM-216289 (
    corresponding disease(s) HHI4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    significantly correlated with a higher recurrence rate of meningiomas
    constitutional     --over  
    in corneal fibroblasts resulted in up-regulation of adherens-junction proteins in corneal epithelial cells, suggesting that fibroblasts promote the terminal differentiation of epithelial cells in the cornea
    Variant & Polymorphism
    Candidate gene
    Therapy target
    is a promising new therapeutic agent in bone and joint diseases
    supplementation of SEMA3A might be used in novel therapeutic antiangiogenic strategies to prevent the recurrence of highly vascularized meningiomas
    Sema3a-/- mice lacked a cardiac sympathetic innervation gradient and exhibited stellate ganglia malformation, leading to a marked sinus bradycardia due to sympathetic dysfunction (
  • mice mutant in the semaIII gene show in the cerebral cortex paucity of neuropil and abnormally oriented neuronal processes, especially of the large pyramidal neurons and certain embryonic bones and cartilaginous structures develop abnormally, with vertebral fusions and partial rib duplications (