SLC7A5
protein-codingsolute carrier family 7 member 5, the group of Solute carrier family 7|MicroRNA protein coding host genes|CD molecules
Gene summary
Enables transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in apical plasma membrane; cytosol; and microvillus membrane. Part of amino acid transport complex. Implicated in cholangiocarcinoma; colon cancer; hepatocellular carcinoma; and lung squamous cell carcinoma. Biomarker of esophagitis; gastrointestinal system cancer (multiple); malignant astrocytoma (multiple); and respiratory system cancer (multiple). [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 ~39.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: ClinGen
*SLC7A5* was first reported in relation to autosomal recessive complex neurodevelopmental disorder in 2016 (Tarlungeanu et al., PMID: 27912058). *SLC7A5* encodes a large neutral amino acid transporter that is critical for maintaining normal levels of brain branched-chain amino acids. The phenotypes in the three families reported to date include global developmental delay, motor deficits, delayed or absent speech, autism, microcephaly, and structural brain abnormalities, with seizures and growth delay in some families. Three variants (2 missense and 1 intragenic deletion) that have been reported in three unrelated probands in two publications (PMIDs: 27912058, 36996814) are included in this curation. Variants in this gene segregated with disease in six additional family members. Two consanguineous families harbored homozygous missense variants (PMID: 27912058), while the third family was compound heterozygous for a previously reported missense variant and an intragenic deletion (PMID: 36996814). The mechanism of pathogenicity is reported to be reduced or loss of function (PMIDs: 27912058). This gene-disease relationship is also supported by studies in fibroblasts from patients showing decreased leucine uptake (PMID: 27912058), and knock-out mouse models (PMIDs: 27912058, 36996814). Pathogenic variants in *BCKDK*, which encodes a regulator of the catabolic pathway of branched-chain amino acids, cause a neurodevelopmental disorder with overlapping features (PMID: 22956686). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has been reported. This gene-disease pair was originally evaluated by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on November 7, 2023. It was reevaluated on July 22, 2026 (SOP Version 12). Although experimental evidence was added, the classification did not change.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC7A5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003486.7. 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 | 4 | 5 | 10 | ||
| missense | 71 | 3 | 3 | 77 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 73 | 7 | 8 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003477.4 | 10 | MANE Select | |
| Ensembl | ENSP00000261622.4 | 10 | MANE Select | |
| Ensembl | ENSP00000454323.1 | 7 | Standard | |
| Ensembl | ENSP00000454323.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- Central carbon metabolism in cancer - Homo sapiens (human)
- Polythiazide Action Pathway
- Methyclothiazide Action Pathway
- Bumetanide Action Pathway
Biological Process
- amino acid transmembrane transport
- cellular amino acid metabolic process
- nervous system development
- neutral amino acid transport
- cell differentiation
Molecular Function
- protein binding
- amino acid transmembrane transporter activity
- neutral amino acid transmembrane transporter activity
- L-amino acid transmembrane transporter activity
- peptide antigen binding
Cellular Component
- cytosol
- plasma membrane
- membrane
- integral component of membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261622
- Coding exons
- 10
- Length
- 39466
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125731
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.65 | 215 | 295 | 0.730 | 0.0000181 | 3208 |
| Missense (PolyPhen) | 76 | 133.47 | 0.56941 | 1493 | ||
| Synonymous | -4.42 | 213 | 145 | 1.47 | 0.0000105 | 1102 |
| Loss of Function | 3.17 | 5 | 20.4 | 0.245 | 9.07e-7 | 232 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular amino acid uptake. Acts as an amino acid exchanger. Involved in the transport of L-DOPA across the blood- brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Plays a role in neuronal cell proliferation (neurogenesis) in brain. 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. May play an important role in high-grade gliomas. Mediates blood-to-retina L- leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts. When associated with LAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567). {ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:16496379, ECO:0000269|PubMed:18262359, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058}.;
Recessive Scores
- pRec
- 0.251
Intolerance Scores
- LoFtool
- 0.0798
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.931
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |