SLC1A4

solute carrier family 1 member 4, the group of Solute carrier family 1

Basic information

Region (hg38): 2:64988477-65023865

Links

ENSG00000115902 ∙ NCBI:6509 ∙ OMIM:600229 ∙ HGNC:10942 ∙ Uniprot:P43007 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome (Strong), mode of inheritance: AR
• spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome (Supportive), mode of inheritance: AR
• spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic tetraplegia, thin corpus callosum, and progressive microcephaly	AR	General	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	Neurologic	25930971; 26041762; 26138499; 29989513; 31763347

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC1A4 gene.

• not provided (10 variants)
• Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC1A4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				180	6	186
missense	1	3	83	4	3	94
nonsense	2	2	1			5
start loss						0
frameshift	7	1				8
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3				4
splice region			2	9		11
non coding			1	39	16	56
Total	11	9	86	223	25

Highest pathogenic variant AF is 0.000105

Variants in SLC1A4

This is a list of pathogenic ClinVar variants found in the SLC1A4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-64989247-TC-T			Benign (May 15, 2021)
2-64989251-GGCGGCGGCTCCC-G			Benign (May 14, 2021)
2-64989311-C-G			Benign (May 20, 2021)
2-64989353-T-C			Benign (May 14, 2021)
2-64989513-C-G			Benign (May 14, 2021)
2-64989514-G-C			Benign (May 14, 2021)
2-64989609-C-T			Benign (May 16, 2021)
2-64989643-C-T			Uncertain significance (Dec 01, 2018)
2-64989645-T-C		Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome	Pathogenic (Mar 01, 2023)
2-64989664-C-A			Benign (Jan 31, 2024)
2-64989679-C-T			Likely benign (Jan 20, 2024)
2-64989683-G-A			Benign/Likely benign (Jul 01, 2024)
2-64989685-T-C		SLC1A4-related disorder	Likely benign (Jan 23, 2023)
2-64989691-G-A			Likely benign (Jun 01, 2024)
2-64989691-G-T			Likely benign (Dec 30, 2023)
2-64989692-G-A			Uncertain significance (May 12, 2022)
2-64989694-G-A			Likely benign (Jan 19, 2024)
2-64989694-G-T			Likely benign (Jan 05, 2023)
2-64989703-C-A			Likely benign (Feb 09, 2023)
2-64989703-C-T			Likely benign (Oct 14, 2023)
2-64989706-G-C			Likely benign (Sep 28, 2023)
2-64989708-C-A			Uncertain significance (Feb 19, 2022)
2-64989708-C-T		SLC1A4-related disorder	Conflicting classifications of pathogenicity (Jan 31, 2024)
2-64989709-C-T			Likely benign (Nov 06, 2023)
2-64989711-G-A			Uncertain significance (Aug 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC1A4	protein_coding	protein_coding	ENST00000234256	8	35389

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0656	0.932	125718	0	29	125747	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.73	219	304	0.721	0.0000165	3366
Missense in Polyphen		121	166.48	0.72681		1859
Synonymous	0.486	128	135	0.947	0.00000812	1179
Loss of Function	2.62	5	16.5	0.303	7.99e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transporter for alanine, serine, cysteine, and threonine. Exhibits sodium dependence. {ECO:0000269|PubMed:26041762}.
• Pathway: Argininemia;Citrullinemia Type I;Carbamoyl Phosphate Synthetase Deficiency;Argininosuccinic Aciduria;Glucose-Alanine Cycle;Urea Cycle;Glutaminolysis and Cancer;Ornithine Transcarbamylase Deficiency (OTC Deficiency);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Tyrosine metabolism;Amino acid transport across the plasma membrane;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Histidine metabolism;Methionine and cysteine metabolism;Glycerophospholipid metabolism;Porphyrin metabolism;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.519
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.36

Haploinsufficiency Scores

• pHI: 0.127
• hipred: Y
• hipred_score: 0.662
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.618

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc1a4

Gene ontology

• Biological process: amino acid transport;glutamine transport;L-alanine transport;L-cystine transport;proline transport;L-serine transport;threonine transport;hydroxyproline transport;synaptic transmission, glutamatergic;proline transmembrane transport;cognition;chloride transmembrane transport
• Cellular component: centrosome;microtubule organizing center;intermediate filament;plasma membrane;integral component of plasma membrane;cell surface;membrane;integral component of membrane;dendrite;melanosome;neuronal cell body;extracellular exosome
• Molecular function: chloride channel activity;amino acid transmembrane transporter activity;L-alanine transmembrane transporter activity;L-cystine transmembrane transporter activity;L-glutamine transmembrane transporter activity;L-proline transmembrane transporter activity;L-serine transmembrane transporter activity;L-threonine transmembrane transporter activity;symporter activity;L-hydroxyproline transmembrane transporter activity