SLC6A20
protein-codingsolute carrier family 6 member 20, the group of Solute carrier family 6
Gene summary
Transport of small hydrophilic substances across cell membranes is mediated by substrate-specific transporter proteins which have been classified into several families of related genes. The protein encoded by this gene belongs to the sodium:neurotransmitter symporter (SNF) family and functions as a proline transporter expressed in kidney and small intestine. Mutations in this gene are associated with Hyperglycinuria and Iminoglycinuria. [provided by RefSeq, Jul 2020]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0007677
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007677
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0007677
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Renal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC6A20 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020208.4. 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 | 7 | 23 | 3 | 33 | ||
| missense | 110 | 8 | 1 | 119 | ||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 124 | 31 | 4 | 159 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064593.1 | 11 | MANE Select | |
| Ensembl | ENSP00000346298.4 | 11 | MANE Select | |
| RefSeq | NP_001372612.1 | 11 | Standard | |
| RefSeq | NP_001392995.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Polythiazide Action Pathway
- Methyclothiazide Action Pathway
- Bumetanide Action Pathway
- Spironolactone Action Pathway
- Eplerenone Action Pathway
Biological Process
- amino acid transport
- glycine transport
- proline transport
- proline transmembrane transport
Molecular Function
- neurotransmitter:sodium symporter activity
- protein binding
- amino acid transmembrane transporter activity
- L-proline transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358525
- Coding exons
- 11
- Length
- 41086
- Individuals with no LoFs
- 125349
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 395
- Defined
- 125748
- p
- 0.00159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.497 | 333 | 359 | 0.926 | 0.0000215 | 3843 |
| Missense (PolyPhen) | 139 | 151.59 | 0.91694 | 1663 | ||
| Synonymous | -0.877 | 180 | 166 | 1.09 | 0.0000118 | 1191 |
| Loss of Function | 0.435 | 27 | 29.6 | 0.914 | 0.00000135 | 313 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00075 | 0.00075 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.010 | 0.0098 | notable |
| European (Non-Finnish) | 0.0012 | 0.0011 | notable |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates the calcium-dependent uptake of imino acids such as L-proline, N-methyl-L-proline and pipecolate as well as N- methylated amino acids. Involved in the transport of glycine. {ECO:0000269|PubMed:15632147, ECO:0000269|PubMed:19033659}.;
- Disease
- DISEASE: Iminoglycinuria (IG) [MIM:242600]: A disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine. {ECO:0000269|PubMed:19033659}. Note=The disease is caused by mutations affecting the gene represented in this entry. Haploinsufficiency of SLC6A20 combined with deficiency of the neutral amino acid transporter SLC6A19 or partially inactivating mutations in SLC36A2, is responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.906
- RVIS EVS
- -0.53
- RVIS percentile EVS
- 20.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.335
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |