SEMA3A |
- 1
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- SEMA3A (HGNC:10723) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- semaphorin 3A
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- SEMAD
- Alias symbols
- SEMA1, SemD, coll-1, Hsema-I
- %HI
- 1.46(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.98(Read more about gnomAD pLI score)
- LOEUF
- 0.31(Read more about gnomAD LOEUF score)
- Cytoband
- 7q21.11
- Genomic Coordinates
-
GRCh37/hg19: chr7:83585093-83824105 NCBI Ensembl UCSC GRCh38/hg38: chr7:83955777-84492725 NCBI Ensembl UCSC - MANE Select Transcript
- NM_006080.3 ENST00000265362.9 (Read more about MANE Select)
- 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}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-30624
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency
(1)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
08/07/2017
Haploinsufficiency (HI) Score Details
HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
22416012
Young et al. (2012) report a family with Kallmann syndrome: a proband and two relatives, with a heterozygous deletion of 213 kb at locus 7q21.11. The deletion includes 11 of 17 exons of SEMA3A and was first identified by genomic microarray and confirmed by RT-qPCR. Sequencing of the SEMA3A exons and intron-exon junctions to assess whether a second mutation was present, was negative. All patients presented with the phenotype. Two of the patients were male and were found to present with hypogonadism and hyposmia. One patient was female and presented with primary amenorrhea, absent breast development, and anosmia. In this family, the Kallmann phenotype was transmitted in an autosomal dominant manner, which suggests that haploinsufficiency of SEMA3A is sufficient to cause the Kallmann phenotype. However, they do not rule out the possibility of a second genetic event that was not revealed by their study.
HI Evidence Comments:
Although SEMA3A deletion has been linked to Kallman syndrome, the inheritance pattern is unclear. Therefore the current haploinsufficiency score is 1. Additional studies with proposed alternative mechanisms of pathogenicity are summarized below.
PMID: 22927827
Hanchate et al. (2012) screened 386 patients with a clinical diagnosis of Kallmann syndrome for mutations in SEMA3A by Sanger sequencing (coding exons and flanking splice sites); some of these patients also carried a molecular diagnosis, with mutation in a known Kallmann syndrome-associated gene. In 24 of these patients they identified 7 missense mutations and 1 small frameshifting deletion. Functional in vitro studies revealed that these mutations resulted in either impaired secretion (consistent with loss of function) or reduced signaling activity of the secreted protein. None of the patients studied were found to carry a second mutation/deletion in SEMA3A. They conclude that the Kallmann syndrome phenotype requires the combination of a mutation/deletion in both SEMA3A and another gene, consistent with an oligogenic pattern of inheritance.
PMID: 24124006
Hofmann et al. (2013) report an individual with bi-allelic alteration of SEMA3A: a deletion of 150 kb that includes the first exon, a coding exon, and a second in-frame mutation in SEMA3A at aa316. The deletion was confirmed to be inherited from an apparently healthy father; however, no additional mutation testing was done. The patient presented with minor facial dysmorphism, skeletal anomalies, and short stature. SEMA3A relative expression was decreased in the patient compared to normal controls. Neither patient showed clinical findings consistent with Kallmann syndrome. The authors conclude that biallelic SEMA3A defects cause a novel short stature syndrome without the typical Kallmann syndrome phenotypic findings.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No literature found.
Genomic View
Select assembly:
(NC_000007.13)
(NC_000007.14)