SEMA7A
protein-codingsemaphorin 7A (John Milton Hagen blood group), the group of Immunoglobulin like domain containing|Semaphorins|CD molecules|MicroRNA protein coding host genes|Blood group antigens
Gene summary
This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
- SEMAL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030815
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal; Hematologic
Intervention: Gastrointestinal; Hematologic
Rationale: Individuals with Cholestasis, progressive familial intrahepatic 11 may benefit from medical management (eg, with ursodeoxycholic acid or glutathione); Variants associated with a blood group may be important in specific situations (eg, related to transfusion)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEMA7A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003612.5. 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 | 1 | 34 | 1 | 36 | ||
| missense | 1 | 88 | 15 | 1 | 105 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 0 | 95 | 49 | 2 | 147 |
Highest pathogenic variant AF is 0.0001902847
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003603.1 | 14 | MANE Select | |
| Ensembl | ENSP00000261918.4 | 14 | MANE Select | |
| RefSeq | NP_001139501.1 | 13 | Standard | |
| RefSeq | NP_001139502.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- Other semaphorin interactions
- Semaphorin interactions
- Axon guidance
Biological Process
- osteoblast differentiation
- neural crest cell migration
- inflammatory response
- immune response
- integrin-mediated signaling pathway
Molecular Function
- integrin binding
- protein binding
- semaphorin receptor binding
- neuropilin binding
- chemorepellent activity
Cellular Component
- extracellular space
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261918
- Coding exons
- 14
- Length
- 25179
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125742
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.84 | 296 | 399 | 0.741 | 0.0000257 | 4314 |
| Missense (PolyPhen) | 68 | 127.21 | 0.53453 | 1426 | ||
| Synonymous | -0.689 | 177 | 166 | 1.07 | 0.0000112 | 1329 |
| Loss of Function | 4.01 | 8 | 32.8 | 0.244 | 0.00000158 | 359 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00020 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of proinflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes. {ECO:0000269|PubMed:12879062, ECO:0000269|PubMed:17377534, ECO:0000269|PubMed:17671519}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.653
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.350
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |