GYPA
protein-codingglycophorin A (MNS blood group), the group of Blood group antigens|CD molecules
Gene summary
Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. [provided by RefSeq, Jul 2008]
- MNS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0020616
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Hematologic
Intervention: Hematologic
Rationale: 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 GYPA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002099.8. 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 | 0 | |||||
| missense | 1 | 16 | 3 | 20 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 16 | 3 | 0 | 20 |
Highest pathogenic variant AF is 0.00001446143
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002090.4 | 7 | MANE Select | |
| Ensembl | ENSP00000493142.2 | 7 | MANE Select | |
| RefSeq | NP_001295116.1 | 6 | Standard | |
| RefSeq | NP_001295119.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Malaria - Homo sapiens (human)
- Hematopoietic cell lineage - Homo sapiens (human)
- Hematopoietic Stem Cell Differentiation
- Cell surface interactions at the vascular wall
- Hemostasis
Biological Process
- viral entry into host cell
- leukocyte migration
Molecular Function
- virus receptor activity
- protein binding
- identical protein binding
Cellular Component
- plasma membrane
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360771
- Coding exons
- 7
- Length
- 31448
- Individuals with no LoFs
- 125659
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125663
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.550 | 94 | 80.2 | 1.17 | 0.00000418 | 928 |
| Missense (PolyPhen) | 28 | 25.834 | 1.0839 | 325 | ||
| Synonymous | -0.0271 | 28 | 27.8 | 1.01 | 0.00000153 | 297 |
| Loss of Function | 1.22 | 6 | 10.2 | 0.588 | 5.16e-7 | 124 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Glycophorin A is the major intrinsic membrane protein of the erythrocyte. The N-terminal glycosylated segment, which lies outside the erythrocyte membrane, has MN blood group receptors. Appears to be important for the function of SLC4A1 and is required for high activity of SLC4A1. May be involved in translocation of SLC4A1 to the plasma membrane. Is a receptor for influenza virus. Is a receptor for Plasmodium falciparum erythrocyte-binding antigen 175 (EBA-175); binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans. Appears to be a receptor for Hepatitis A virus (HAV). {ECO:0000269|PubMed:10926825, ECO:0000269|PubMed:12813056, ECO:0000269|PubMed:14604989, ECO:0000269|PubMed:15331714, ECO:0000269|PubMed:19438409, ECO:0000269|PubMed:8009226}.;
Intolerance Scores
- LoFtool
- 0.769
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 76.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.231
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |