SLC4A7
protein-codingsolute carrier family 4 member 7, the group of Solute carrier family 4
Gene summary
This locus encodes a sodium bicarbonate cotransporter. The encoded transmembrane protein appears to transport sodium and bicarbonate ions in a 1:1 ratio, and is thus considered an electroneutral cotransporter. The encoded protein likely plays a critical role in regulation of intracellular pH involved in visual and auditory sensory transmission. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]
- SLC4A6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~111.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019200
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0015993
Submitter: Franklin by Genoox
A 66-year-old male with progressive rod-cone dystrophy with varied retinal degrenagtion phenotype underwent DNA examination which revealed a homozygous frameshift mutation in SLC4A7
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC4A7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001321103.2. 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 | 3 | 7 | 10 | |||
| missense | 111 | 4 | 115 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 121 | 11 | 0 | 132 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001308032.1 | 26 | MANE Select | |
| Ensembl | ENSP00000390394.1 | 26 | MANE Select | |
| RefSeq | NP_001245308.1 | 25 | Standard | |
| RefSeq | NP_001245309.1 | 24 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- Transport of inorganic cations/anions and amino acids/oligopeptides
- SLC-mediated transmembrane transport
- Transport of small molecules
Biological Process
- sodium ion transport
- inorganic anion transport
- bicarbonate transport
- regulation of intracellular pH
- auditory receptor cell development
Molecular Function
- inorganic anion exchanger activity
- sodium:bicarbonate symporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
- basolateral plasma membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295736
- Coding exons
- 25
- Length
- 111698
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125746
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.25 | 485 | 646 | 0.751 | 0.0000334 | 7919 |
| Missense (PolyPhen) | 168 | 301.12 | 0.55791 | 3718 | ||
| Synonymous | -0.662 | 235 | 222 | 1.06 | 0.0000114 | 2361 |
| Loss of Function | 5.54 | 12 | 57.2 | 0.210 | 0.00000309 | 741 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00020 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry. Regulates intracellular pH and may play a role in bicarbonate salvage in secretory epithelia. May also have an associated sodium channel activity. {ECO:0000269|PubMed:10347222, ECO:0000269|PubMed:12403779}.;
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- LoFtool
- 0.469
- RVIS EVS
- -0.97
- RVIS percentile EVS
- 8.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.511
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |