SLC4A1
solute carrier family 4 member 1 (Diego blood group), the group of Blood group antigens|CD molecules|Solute carrier family 4
Basic information
Region (hg38): 17:44248390-44268141
Previous symbols: [ "EPB3", "AE1", "DI", "WD" ]
Links
Phenotypes
GenCC
Source:
- hereditary spherocytosis (Supportive), mode of inheritance: AD
- dehydrated hereditary stomatocytosis (Supportive), mode of inheritance: AD
- autosomal dominant distal renal tubular acidosis (Supportive), mode of inheritance: AD
- renal tubular acidosis, distal, 4, with hemolytic anemia (Supportive), mode of inheritance: AD
- southeast Asian ovalocytosis (Supportive), mode of inheritance: AD
- cryohydrocytosis (Supportive), mode of inheritance: AD
- renal tubular acidosis, distal, 4, with hemolytic anemia (Strong), mode of inheritance: AR
- autosomal dominant distal renal tubular acidosis (Strong), mode of inheritance: AD
- southeast Asian ovalocytosis (Strong), mode of inheritance: AD
- cryohydrocytosis (Limited), mode of inheritance: Unknown
- hereditary spherocytosis type 4 (Strong), mode of inheritance: AD
- autosomal dominant distal renal tubular acidosis (Strong), mode of inheritance: AD
- autosomal dominant distal renal tubular acidosis (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Spherocytosis, type 4; Ovalcytosis, Southeast Asian; Cryohydrocytosis; Renal tubular acidosis, distal, with hemolytic anemia; Renal tubular acidosis, distal, 1; Renal tubular acidosis, distal, autosomal recessive; Blood group, Wright; Blood group, Waldner; Blood group, Diego; Blood group, Froese; Blood group, Swann | AD/AR/BG | Hematologic; Renal | In Renal tubular acidosis, if detected early, therapeutic correction of the acidosis by alkali administration leads in most cases to improvement of biochemical abnormalities and resumption of normal growth, as well as beneficial regarding skeletal manifestations; As pertains to hematologic manifestations, splenectomy has been reported as being beneficial; Variants associated with a blood group may be important in specific situations (eg, related to transfusion) | Hematologic; Renal | 13288586; 13669428; 13739450; 6025225; 2829189; 2146504; 1824272; 1536803; 1519367; 1737855; 1520883; 8343110; 7713501; 8206915; 8282779; 7919393; 7812009; 8547122; 8704215; 8608262; 8567957; 9207478; 9312167; 9734643; 9973643; 9600966; 9854053; 10403343; 10926824; 11061863; 10942416; 11155072; 11380459; 11756190; 12087557; 15211439; 16227998; 19229254; 19297287; 20015879; 20799361; 20825599; 20960171; 22126643; 22609520; 22693689; 22919024; 23255290; 23498825; 23878048; 24257694 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (628 variants)
- Hereditary_spherocytosis_type_4 (241 variants)
- Autosomal_dominant_distal_renal_tubular_acidosis (221 variants)
- Renal_tubular_acidosis,_distal,_4,_with_hemolytic_anemia (162 variants)
- Cryohydrocytosis (160 variants)
- BLOOD_GROUP--DIEGO_SYSTEM (152 variants)
- BLOOD_GROUP--FROESE (152 variants)
- Southeast_Asian_ovalocytosis (152 variants)
- BLOOD_GROUP--SWANN_SYSTEM (151 variants)
- BLOOD_GROUP--WALDNER_TYPE (151 variants)
- BLOOD_GROUP--WRIGHT_ANTIGEN (151 variants)
- Malaria,_susceptibility_to (151 variants)
- Inborn_genetic_diseases (95 variants)
- Hemolytic_anemia (69 variants)
- SLC4A1-related_disorder (38 variants)
- not_specified (25 variants)
- Distal_renal_tubular_acidosis (4 variants)
- Renal_tubular_acidosis (4 variants)
- Distal_Renal_Tubular_Acidosis,_Dominant (3 variants)
- Spherocytosis,_Dominant (3 variants)
- SWANN_BLOOD_GROUP_ANTIGEN (2 variants)
- Acanthocytosis (1 variants)
- Hereditary_spherocytosis (1 variants)
- Autosomal_recessive_distal_renal_tubular_acidosis (1 variants)
- Renal_tubulopathies (1 variants)
- Acanthocytosis_due_to_band_3_HT (1 variants)
- Malaria,_cerebral,_resistance_to (1 variants)
- Bronchiectasis_with_or_without_elevated_sweat_chloride_3 (1 variants)
- DIEGO_BLOOD_GROUP_ANTIGEN (1 variants)
- Renal_tubular_acidosis,_distal,_with_normal_red_cell_morphology (1 variants)
- Spherocytosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC4A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000342.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | 91 | 113 | |||
| missense | 12 | 40 | 333 | 44 | 431 | |
| nonsense | 18 | 18 | 38 | |||
| start loss | 0 | |||||
| frameshift | 24 | 66 | 95 | |||
| splice donor/acceptor (+/-2bp) | 12 | 23 | 36 | |||
| Total | 66 | 149 | 353 | 135 | 10 |
Highest pathogenic variant AF is 0.000029755189
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SLC4A1 | protein_coding | protein_coding | ENST00000262418 | 19 | 19757 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.846 | 0.154 | 125737 | 0 | 11 | 125748 | 0.0000437 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 426 | 534 | 0.798 | 0.0000353 | 5848 |
| Missense in Polyphen | 162 | 231.02 | 0.70124 | 2545 | ||
| Synonymous | -0.575 | 241 | 230 | 1.05 | 0.0000155 | 1935 |
| Loss of Function | 4.81 | 8 | 41.4 | 0.193 | 0.00000214 | 456 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000904 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000534 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein. Major integral membrane glycoprotein of the erythrocyte membrane; required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin. Functions as a transporter that mediates the 1:1 exchange of inorganic anions across the erythrocyte membrane. Mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine. {ECO:0000269|PubMed:10926824, ECO:0000269|PubMed:14734552, ECO:0000269|PubMed:1538405, ECO:0000269|PubMed:20151848, ECO:0000269|PubMed:24121512}.;
- Disease
- DISEASE: Ovalocytosis, Southeast Asian (SAO) [MIM:166900]: A hereditary hematologic disorder characterized by ovalocytic erythrocytes that are rigid and exhibit reduced expression of many erythrocyte antigens. Clinical manifestations include mild hemolysis, intermittent jaundice and gallstones. However, the disorder is most often asymptomatic. {ECO:0000269|PubMed:1538405, ECO:0000269|PubMed:1722314}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spherocytosis 4 (SPH4) [MIM:612653]: Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. {ECO:0000269|PubMed:10580570, ECO:0000269|PubMed:10745622, ECO:0000269|PubMed:10942416, ECO:0000269|PubMed:11380459, ECO:0000269|PubMed:1378323, ECO:0000269|PubMed:15813913, ECO:0000269|PubMed:16227998, ECO:0000269|PubMed:7530501, ECO:0000269|PubMed:8547122, ECO:0000269|PubMed:8640229, ECO:0000269|PubMed:8943874, ECO:0000269|PubMed:9012689, ECO:0000269|PubMed:9207478, ECO:0000269|PubMed:9233560, ECO:0000269|PubMed:9973643}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Renal tubular acidosis, distal, autosomal dominant (AD- dRTA) [MIM:179800]: An autosomal dominant disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha- intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Renal tubular acidosis, distal, with hemolytic anemia (dRTA-HA) [MIM:611590]: A disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. {ECO:0000269|PubMed:10926824, ECO:0000269|PubMed:15211439, ECO:0000269|PubMed:9854053}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Renal tubular acidosis, distal, with normal red cell morphology (dRTA-NRC) [MIM:611590]: A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha- intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. {ECO:0000269|PubMed:15211439}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cryohydrocytosis (CHC) [MIM:185020]: An autosomal dominant disorder of red cell membrane permeability characterized by cold-induced changes in cell volume, resulting in cold- sensitive stomatocytosis, and increased erythrocyte osmotic fragility and autohemolysis at 4 degrees Celsius. Patients present with mild to moderate hemolytic anemia, splenomegaly, fatigue, and pseudohyperkalemia due to a potassium leak from the erythrocytes. {ECO:0000269|PubMed:16227998}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.;
- Pathway
- Collecting duct acid secretion - Homo sapiens (human);O2/CO2 exchange in erythrocytes;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Erythrocytes take up oxygen and release carbon dioxide;Bicarbonate transporters;Erythrocytes take up carbon dioxide and release oxygen
(Consensus)
Recessive Scores
- pRec
- 0.577
Intolerance Scores
- loftool
- 0.160
- rvis_EVS
- -0.79
- rvis_percentile_EVS
- 12.62
Haploinsufficiency Scores
- pHI
- 0.110
- hipred
- Y
- hipred_score
- 0.602
- ghis
- 0.671
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.917
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Slc4a1
- Phenotype
- muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- slc4a1b
- Affected structure
- neuromast hair cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased efficacy
Gene ontology
- Biological process
- anion transport;chloride transport;cellular ion homeostasis;bicarbonate transport;regulation of intracellular pH;chloride transmembrane transport
- Cellular component
- plasma membrane;integral component of plasma membrane;integral component of membrane;basolateral plasma membrane;Z disc;cortical cytoskeleton;extracellular exosome;blood microparticle
- Molecular function
- inorganic anion exchanger activity;protein binding;anion transmembrane transporter activity;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;anion:anion antiporter activity;ankyrin binding;protein homodimerization activity;protein membrane anchor