RHAG
Rh associated glycoprotein, the group of CD molecules|Solute carrier family 42|Blood group antigens
Basic information
Region (hg38): 6:49605174-49636839
Links
Phenotypes
GenCC
Source:
- overhydrated hereditary stomatocytosis (Strong), mode of inheritance: AD
- overhydrated hereditary stomatocytosis (Supportive), mode of inheritance: AD
- Rh deficiency syndrome (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Overhydrated hereditary stomatocytosis; Anemia, hemolytic, Rh-null, regulator type; Anemia, hemolytic,Rh-Mod type; RHAG blood group | AD/AR/BG | Hematologic | Individuals can suffer severe anemia, which can be ameliorated by splenectomy (though splenectomy may be less beneficial in Overhydrated hereditary stomatocytosis); Individuals with Overhydrated hereditary stomatocytosis may be prone to iron overload as well as postsplenectomy thrombotic complications, and awareness may allow surveillance and management; Variants associated with a blood group may be important in specific situations (eg, related to transfusion) | Hematologic | 4628355; 3103426; 8563755; 8639421; 9442063; 9454778; 9746795; 9915949; 10467273; 11961248; 18931342; 19744193 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (52 variants)
- Rh-null, regulator type (8 variants)
- Inborn genetic diseases (6 variants)
- Overhydrated hereditary stomatocytosis (5 variants)
- Rh mod blood group phenotype (2 variants)
- altered red cell phenotype (1 variants)
- Rh-null, regulator type;Overhydrated hereditary stomatocytosis (1 variants)
- - (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHAG gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 6 | 24 | 4 | 34 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| inframe indel | 0 | |||||
| splice variant | 3 | 1 | 2 | 1 | 1 | 8 |
| non coding | 1 | 1 | 17 | 19 | ||
| Total | 13 | 1 | 28 | 7 | 19 |
Highest pathogenic variant AF is 0.0000460
Variants in RHAG
This is a list of pathogenic ClinVar variants found in the RHAG region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-49606641-G-T | Benign (Jun 19, 2021) | |||
| 6-49606856-A-G | Uncertain significance (Jun 06, 2022) | |||
| 6-49606895-C-T | Uncertain significance (Jan 24, 2023) | |||
| 6-49606913-G-T | Inborn genetic diseases | Uncertain significance (Oct 12, 2022) | ||
| 6-49606921-C-A | Rh-null, regulator type | Pathogenic (Jan 01, 1999) | ||
| 6-49606923-T-C | Likely pathogenic (Nov 09, 2017) | |||
| 6-49606928-C-T | Benign (Sep 16, 2022) | |||
| 6-49607180-C-T | Inborn genetic diseases | Uncertain significance (Aug 13, 2021) | ||
| 6-49607187-G-A | Uncertain significance (Nov 14, 2022) | |||
| 6-49607194-A-C | Uncertain significance (Nov 02, 2022) | |||
| 6-49607201-CT-C | Rh-null, regulator type | Pathogenic (Feb 01, 1996) | ||
| 6-49607203-G-A | Inborn genetic diseases | Uncertain significance (Mar 24, 2023) | ||
| 6-49607246-A-G | Uncertain significance (Oct 13, 2020) | |||
| 6-49611016-T-C | Likely benign (Oct 09, 2018) | |||
| 6-49611021-C-T | Uncertain significance (Nov 29, 2021) | |||
| 6-49611023-C-T | Rh-null, regulator type | Pathogenic (Sep 01, 1999) | ||
| 6-49611084-A-G | Overhydrated hereditary stomatocytosis | Uncertain significance (Jun 27, 2017) | ||
| 6-49611096-T-C | Uncertain significance (Aug 05, 2022) | |||
| 6-49611101-G-A | Likely benign (Sep 05, 2018) | |||
| 6-49611117-T-C | Overhydrated hereditary stomatocytosis | Uncertain significance (Sep 16, 2022) | ||
| 6-49611133-T-A | Uncertain significance (Dec 21, 2022) | |||
| 6-49611146-C-T | Rh-null, regulator type | Pathogenic (Oct 01, 1998) | ||
| 6-49611163-A-C | Benign (Sep 25, 2022) | |||
| 6-49611163-A-G | Benign (Nov 01, 2022) | |||
| 6-49611245-A-G | Benign (Nov 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RHAG | protein_coding | protein_coding | ENST00000371175 | 10 | 31682 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0104 | 0.988 | 125733 | 0 | 14 | 125747 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.774 | 187 | 219 | 0.853 | 0.0000110 | 2688 |
| Missense in Polyphen | 67 | 99.17 | 0.67561 | 1248 | ||
| Synonymous | -1.53 | 98 | 80.5 | 1.22 | 0.00000455 | 811 |
| Loss of Function | 2.73 | 7 | 20.2 | 0.346 | 0.00000122 | 217 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000969 | 0.0000967 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Associated with rhesus blood group antigen expression (PubMed:19744193). May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane (PubMed:11062476, PubMed:11861637). Involved in ammonia transport across the erythrocyte membrane (PubMed:21849667, PubMed:22012326). Seems to act in monovalent cation transport (PubMed:18931342, PubMed:21849667). {ECO:0000269|PubMed:11062476, ECO:0000269|PubMed:11861637, ECO:0000269|PubMed:18931342, ECO:0000269|PubMed:19744193, ECO:0000269|PubMed:21849667, ECO:0000269|PubMed:22012326}.;
- Disease
- DISEASE: Regulator type Rh-null hemolytic anemia (RHN) [MIM:268150]: Form of chronic hemolytic anemia in which the red blood cells have a stomatocytosis and spherocytosis morphology, an increased osmotic fragility, an altered ion transport system, and abnormal membrane phospholipid organization. {ECO:0000269|PubMed:10467273, ECO:0000269|PubMed:8563755, ECO:0000269|PubMed:9454778, ECO:0000269|PubMed:9716608}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Overhydrated hereditary stomatocytosis (OHST) [MIM:185000]: An autosomal dominant disorder of red cell membrane permeability to monovalent cations, characterized by macrocytic hemolytic anemia of fluctuating severity, circulating erythrocytes with slit-like lucencies (stomata) evident on fixed, stained peripheral blood smears. OHST red cells exhibit cation leak, resulting in elevated cell sodium content with reduced potassium content. The disease is marked by splenomegaly or hepatosplenomegaly, cholelithiasis and a strong tendency for iron overload. {ECO:0000269|PubMed:18931342, ECO:0000269|PubMed:21849667, ECO:0000269|PubMed:22012326}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Amine compound SLC transporters;O2/CO2 exchange in erythrocytes;Rhesus glycoproteins mediate ammonium transport.;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Erythrocytes take up oxygen and release carbon dioxide;Erythrocytes take up carbon dioxide and release oxygen
(Consensus)
Recessive Scores
- pRec
- 0.0760
Intolerance Scores
- loftool
- 0.437
- rvis_EVS
- -0.05
- rvis_percentile_EVS
- 50.22
Haploinsufficiency Scores
- pHI
- 0.990
- hipred
- Y
- hipred_score
- 0.655
- ghis
- 0.438
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.278
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rhag
- Phenotype
- homeostasis/metabolism phenotype; hematopoietic system phenotype;
Zebrafish Information Network
- Gene name
- rhag
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- curved
Gene ontology
- Biological process
- cellular ion homeostasis;carbon dioxide transport;monovalent inorganic cation transport;ammonium transport;bicarbonate transport;carbon dioxide transmembrane transport;erythrocyte development;multicellular organismal iron ion homeostasis;ammonium transmembrane transport
- Cellular component
- plasma membrane;integral component of plasma membrane;membrane
- Molecular function
- ammonium transmembrane transporter activity;leak channel activity;ankyrin binding;carbon dioxide transmembrane transporter activity