SLC14A1
protein-codingsolute carrier family 14 member 1 (Kidd blood group), the group of Solute carrier family 14|Blood group antigens
Gene summary
The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system. [provided by RefSeq, Mar 2009]
- JK
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~65.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0020612
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016383
Submitter: ClinGen
No convincing evidence for a causal role for SLC14A1 in nephrogenic diabetes insipidus has been reported. Although this gene-disease association is supported by a mouse model demonstrating urinary anomalies such as polydipsia and reduced urea permeability (PMID: 11792714), no reports have directly implicated the gene in humans. This classification was approved by the ClinGen Tubulopathy GCEP on the meeting date 03/05/2025 (SOP Version 11).
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); Jk deficiency may be associated with a urine concentration defect
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC14A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015865.7. 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 | 1 | 2 | 3 | |||
| missense | 1 | 44 | 4 | 3 | 52 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 1 | 4 | ||
| Total | 3 | 2 | 47 | 4 | 5 | 61 |
Highest pathogenic variant AF is 0.000819013
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056949.4 | 8 | MANE Select | |
| Ensembl | ENSP00000318546.4 | 8 | MANE Select | |
| RefSeq | NP_001122060.3 | 9 | Standard | |
| RefSeq | NP_001139508.2 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| slc14a2 | Danio rerio | Structure: urea transport Quality: decreased rate abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amine compound SLC transporters
- Purine metabolism
- Transport of bile salts and organic acids, metal ions and amine compounds
- SLC-mediated transmembrane transport
- Transport of small molecules
Biological Process
- water transport
- urea transport
- transmembrane transport
- urea transmembrane transport
Molecular Function
- water transmembrane transporter activity
- urea transmembrane transporter activity
- urea channel activity
Cellular Component
- nucleolus
- plasma membrane
- integral component of plasma membrane
- basolateral plasma membrane
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000436407
- Coding exons
- 9
- Length
- 28394
- Individuals with no LoFs
- 125489
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 258
- Defined
- 125748
- p
- 0.00103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00926 | 246 | 246 | 1.00 | 0.0000135 | 2887 |
| Missense (PolyPhen) | 62 | 62.166 | 0.99732 | 789 | ||
| Synonymous | -0.103 | 96 | 94.7 | 1.01 | 0.00000590 | 909 |
| Loss of Function | -0.127 | 20 | 19.4 | 1.03 | 8.54e-7 | 235 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.011 | 0.011 | notable |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Urea channel that facilitates transmembrane urea transport down a concentration gradient. A constriction of the transmembrane channel functions as selectivity filter through which urea is expected to pass in dehydrated form. The rate of urea conduction is increased by hypotonic stress. Plays an important role in the kidney medulla collecting ducts, where it allows rapid equilibration between the lumen of the collecting ducts and the interstitium, and thereby prevents water loss driven by the high concentration of urea in the urine. Facilitates urea transport across erythrocyte membranes. May also play a role in transmembrane water transport, possibly by indirect means.;
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.982
- RVIS EVS
- 0.55
- RVIS percentile EVS
- 81.55
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.200
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |