SLC38A8 (solute carrier family 38 member 8)

Gene

• Entrez ID: 146167
• Gene name: Solute carrier family 38 member 8
• Gene symbol: SLC38A8
• Synonyms (NCBI Gene): FHASD, FVH2, SNAT8
• Chromosome: 16
• Chromosome location: 16q23.3
• Summary: This gene encodes a putative sodium-dependent amino-acid/proton antiporter. The protein has eleven transmembrane domains, an extracellular N-terminus and an intracellular C-terminal tail. The protein is a member of the SLC38 sodium-coupled neutral amino a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139373929	T>G	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs146899328	G>A,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs149592537	G>A	Pathogenic	Coding sequence variant, stop gained
rs372929441	C>A,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs587777253	A>C	Pathogenic	Missense variant, coding sequence variant
rs587777254	A>T	Pathogenic	Missense variant, coding sequence variant
rs587777255	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs587777256	C>T	Pathogenic	Missense variant, coding sequence variant
rs587777257	CAG>-	Pathogenic	Inframe deletion, coding sequence variant
rs756501758	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs760391436	C>T	Likely-pathogenic	Intron variant
rs1057516193	G>C	Likely-pathogenic	Intron variant
rs1057521634	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs1597273765	AG>-	Pathogenic	Coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003333	Process	Amino acid transmembrane transport	IBA
GO:0003406	Process	Retinal pigment epithelium development	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005938	Component	Cell cortex	IEA
GO:0006531	Process	Aspartate metabolic process	IEA
GO:0006865	Process	Amino acid transport	IEA
GO:0007601	Process	Visual perception	IEA
GO:0009615	Process	Response to virus	IEA
GO:0015179	Function	L-amino acid transmembrane transporter activity	IBA
GO:0016020	Component	Membrane	IBA
GO:0016020	Component	Membrane	IEA
GO:0019079	Process	Viral genome replication	IEA
GO:0021554	Process	Optic nerve development	IEA
GO:0030424	Component	Axon	IEA
GO:0031175	Process	Neuron projection development	IEA
GO:0042995	Component	Cell projection	IEA
GO:0060041	Process	Retina development in camera-type eye	IEA
GO:1902475	Process	L-alpha-amino acid transmembrane transport	IEA

Other IDs

• MIM: 615585
• HGNC: 32434
• e!Ensembl: ENSG00000166558

Protein

• UniProt ID: A6NNN8
• Protein name: Solute carrier family 38 member 8 (Amino acid transporter SLC38A8)
• Protein function: Electrogenic sodium-dependent amino acid transporter with a preference for L-glutamine, L-alanine, L-histidine, L-aspartate and L-arginine. May facilitate glutamine uptake in both excitatory and inhibitory neurons. The transport mechanism and st
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01490	Aa_trans	22 → 431	Transmembrane amino acid transporter protein	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in fetal and adult brain, and spinal cord. In the brain, it is localized in the cell body and axon of the majority of neuronal cells and in a subset of glial cells. Found throughout the neuronal retina, with higher expression
• Sequence:

  MEGQTPGSRGLPEKPHPATAAATLSSMGAVFILMKSALGAGLLNFPWAFSKAGGVVPAFL
  VELVSLVFLISGLVILGYAAAVSGQATYQGVVRGLCGPAIGKLCEACFLLNLLMISVAFL
  RVIGDQLEKLCDSLLSGTPPAPQPWYADQRFTLPLLSVLVILPLSAPREIAFQKYTSILG
  TLAACYLALVITVQYYLWPQGLVRESHPSLSPASWTSVFSVFPTICFGFQCHEAAVSIYC
  SMRKRSLSHWALVSVLSLLACCLIYSLTGVYGFLTFGTEVSADVLMSYPGNDMVIIVARV
  LFAVSIVTVYPIVLFLGRSVMQDFWRRSCLGGWGPSALADPSGLWVRMPLTILWVTVTLA
  MALFMPDLSEIVSIIGGISSFFIFIFPGLCLICAMGVEPIGPRVKCCLEVWGVVSVLVGT
  FIFGQSTAAAVWEMF

• Sequence length: 435

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Foveal hypoplasia	Pathogenic	rs587777253, rs1597273765	RCV001003224 RCV001003223	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome	Pathogenic; Likely pathogenic	rs2151131708, rs587777253, rs372929441, rs149592537, rs1228073295, rs149436446, rs1379690075, rs763615950, rs747905946, rs2085268536, rs1463272578, rs777138837, rs1264151343, rs2507616467, rs1057516193, rs1057521634, rs1597273765, rs2085112203, rs1473492838, rs752802453, rs761388176	RCV001733534 RCV000111467 RCV000111471 RCV002490757 RCV001783765 RCV002246723 RCV002271983 RCV005014990 RCV004796848 RCV005356545 RCV005015033 RCV005240961 RCV005015043 RCV004547400 RCV004577099 RCV000408871 RCV001255623 RCV001007575 RCV001270482 RCV001270484 RCV001270483 RCV001270481	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Foveal hypoplasia 2 and optic nerve misrouting with or without anterior segment dysgenesis	Likely pathogenic; Pathogenic	rs149592537, rs587777257	RCV000111472 RCV000111473	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
FOVEAL HYPOPLASIA 2 WITH OPTIC NERVE MISROUTING	Pathogenic	rs587777256	RCV000111470	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
FOVEAL HYPOPLASIA 2 WITH OPTIC NERVE MISROUTING AND ANTERIOR SEGMENT DYSGENESIS	Pathogenic	rs587777254, rs587777255	RCV000111468 RCV000111469	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CIRRHOSIS OF LIVER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leber congenital amaurosis	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Malignant tumor of esophagus	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SLC38A8-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Albinism	Albinism	BEFREE	24290379		★☆☆☆☆ Found in Text Mining only
Albinism	Albinism	Pubtator	32744312, 33808351, 35157951	Associate	★☆☆☆☆ Found in Text Mining only
Albinism, Ocular	Ocular albinism	BEFREE	30942644		★☆☆☆☆ Found in Text Mining only
Anterior segment mesenchymal dysgenesis	Anterior segment mesenchymal dysgenesis	Pubtator	32744312, 33498813	Associate	★☆☆☆☆ Found in Text Mining only
Color Vision Defects	Color vision deficiency	Pubtator	35157951	Associate	★☆☆☆☆ Found in Text Mining only
FOVEAL HYPOPLASIA 2	Foveal hypoplasia	GENOMICS_ENGLAND_DG	24045842		★☆☆☆☆ Found in Text Mining only
FOVEAL HYPOPLASIA 2	Foveal hypoplasia	UNIPROT_DG	24045842, 24290379		★☆☆☆☆ Found in Text Mining only
FOVEAL HYPOPLASIA 2	Foveal hypoplasia	ORPHANET_DG	24290379		★☆☆☆☆ Found in Text Mining only
FOVEAL HYPOPLASIA 2	Foveal hypoplasia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
FOVEAL HYPOPLASIA 2 WITH OPTIC NERVE MISROUTING	Foveal hypoplasia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
FOVEAL HYPOPLASIA 2 WITH OPTIC NERVE MISROUTING AND ANTERIOR SEGMENT DYSGENESIS	Foveal hypoplasia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Foveal Hypoplasia and Anterior Segment Dysgenesis	Foveal hypoplasia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome	Foveal hypoplasia	Orphanet			★☆☆☆☆ Found in Text Mining only
Leber Congenital Amaurosis	Leber Congenital Amaurosis	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	23213074		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nystagmus	Nystagmus	BEFREE	24045842		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus Pathologic	Nystagmus	Pubtator	32744312, 33498813	Associate	★☆☆☆☆ Found in Text Mining only
Ocular albinism, type I	Ocular albinism	BEFREE	31719542		★☆☆☆☆ Found in Text Mining only