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GeneBe

RHAG

Rh associated glycoprotein, the group of CD molecules|Solute carrier family 42|Blood group antigens

Basic information

Region (hg38): 6:49605174-49636839

Links

ENSG00000112077NCBI:6005OMIM:180297HGNC:10006Uniprot:Q02094AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • overhydrated hereditary stomatocytosis (Strong), mode of inheritance: AD
  • overhydrated hereditary stomatocytosis (Supportive), mode of inheritance: AD
  • Rh deficiency syndrome (Supportive), mode of inheritance: AR
  • Rh deficiency syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Overhydrated hereditary stomatocytosis; Anemia, hemolytic, Rh-null, regulator type; Anemia, hemolytic,Rh-Mod type; RHAG blood groupAD/AR/BGHematologicIndividuals 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)Hematologic4628355; 3103426; 8563755; 8639421; 9442063; 9454778; 9746795; 9915949; 10467273; 11961248; 18931342; 19744193

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RHAG gene.

  • not provided (61 variants)
  • Inborn genetic diseases (8 variants)
  • RHAG-related condition (3 variants)
  • Rh-null, regulator type (3 variants)
  • not specified (2 variants)
  • Overhydrated hereditary stomatocytosis (2 variants)
  • Overhydrated hereditary stomatocytosis;Rh-null, regulator type (1 variants)
  • Rh deficiency syndrome (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.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
2
clinvar
1
clinvar
2
clinvar
5
missense
1
clinvar
35
clinvar
3
clinvar
39
nonsense
1
clinvar
1
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
3
splice region
2
1
2
5
non coding
1
clinvar
1
clinvar
17
clinvar
19
Total 4 1 38 5 19

Highest pathogenic variant AF is 0.0000460

Variants in RHAG

This is a list of pathogenic ClinVar variants found in the RHAG region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
6-49606641-G-T Benign (Jun 19, 2021)1221020
6-49606843-A-G Benign (Nov 30, 2023)2727778
6-49606856-A-G Uncertain significance (Jun 06, 2022)2435419
6-49606895-C-G Likely benign (May 01, 2024)3239107
6-49606895-C-T Uncertain significance (Jan 24, 2023)2435424
6-49606913-G-T not specified Uncertain significance (Sep 27, 2023)1050684
6-49606921-C-A Rh-null, regulator type Pathogenic (Jan 01, 1999)13066
6-49606923-T-C Likely pathogenic (Nov 09, 2017)1068333
6-49606928-C-T Benign (Oct 24, 2023)1670237
6-49606929-G-A RHAG-related disorder Likely benign (Jul 11, 2019)3050561
6-49607176-G-A not specified Uncertain significance (Dec 19, 2023)3153953
6-49607180-C-T not specified Uncertain significance (Aug 13, 2021)2244914
6-49607181-G-A Benign (Nov 13, 2023)2712934
6-49607187-G-A Uncertain significance (Nov 14, 2022)2435427
6-49607194-A-C Uncertain significance (Nov 02, 2022)2435425
6-49607201-CT-C Rh-null, regulator type Pathogenic (Feb 01, 1996)13058
6-49607203-G-A not specified Uncertain significance (Mar 24, 2023)2529239
6-49607246-A-G Uncertain significance (Oct 13, 2020)1163265
6-49611016-T-C Likely benign (Oct 09, 2018)792184
6-49611021-C-T Uncertain significance (Jan 19, 2024)1354370
6-49611023-C-T Rh-null, regulator type • Rh deficiency syndrome Pathogenic (Sep 18, 2023)13064
6-49611034-C-T RHAG-related disorder Likely benign (Apr 10, 2023)2902956
6-49611073-C-T RHAG-related disorder • not specified Uncertain significance (Sep 29, 2023)2634109
6-49611076-C-T Uncertain significance (Nov 07, 2023)2975144
6-49611084-A-G Overhydrated hereditary stomatocytosis Uncertain significance (Jun 27, 2017)438647

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RHAGprotein_codingprotein_codingENST00000371175 1031682
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.01040.9881257330141257470.0000557
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7741872190.8530.00001102688
Missense in Polyphen6799.170.675611248
Synonymous-1.539880.51.220.00000455811
Loss of Function2.73720.20.3460.00000122217

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.00009930.0000992
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00009690.0000967
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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