SLC7A8
protein-codingsolute carrier family 7 member 8, the group of Solute carrier family 7
Gene summary
Enables protein heterodimerization activity and transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in basolateral plasma membrane and microvillus membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~58.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC7A8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012244.4. 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 | 1 | 2 | 3 | |||
| missense | 2 | 72 | 1 | 2 | 77 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 7 | 8 | |||
| Total | 0 | 3 | 81 | 3 | 2 | 89 |
Highest pathogenic variant AF is 0.000014870276
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036376.2 | 11 | MANE Select | |
| Ensembl | ENSP00000320378.7 | 11 | MANE Select | |
| RefSeq | NP_001253965.1 | 9 | Standard | |
| RefSeq | NP_001253966.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein digestion and absorption - Homo sapiens (human)
- Polythiazide Action Pathway
- Methyclothiazide Action Pathway
- Bumetanide Action Pathway
- Spironolactone Action Pathway
Biological Process
- amino acid transmembrane transport
- cellular amino acid metabolic process
- amino acid transport
- response to toxic substance
- organic cation transport
Molecular Function
- protein binding
- organic cation transmembrane transporter activity
- amino acid transmembrane transporter activity
- neutral amino acid transmembrane transporter activity
- L-amino acid transmembrane transporter activity
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316902
- Coding exons
- 11
- Length
- 58380
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 49
- Defined
- 125748
- p
- 0.000195
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.174 | 299 | 308 | 0.972 | 0.0000169 | 3428 |
| Missense (PolyPhen) | 143 | 157.75 | 0.90647 | 1751 | ||
| Synonymous | 0.476 | 123 | 130 | 0.947 | 0.00000771 | 1130 |
| Loss of Function | 1.58 | 15 | 23.2 | 0.646 | 0.00000107 | 267 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00083 | 0.00083 | rare |
| European (Non-Finnish) | 0.00018 | 0.00017 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sodium-independent, high-affinity transport of small and large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Plays an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney. {ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15081149, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15918515}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.135
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.966
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |