SLC16A1

solute carrier family 16 member 1, the group of Solute carrier family 16

Basic information

Region (hg38): 1:112911846-112957593

Links

ENSG00000155380 ∙ NCBI:6566 ∙ OMIM:600682 ∙ HGNC:10922 ∙ Uniprot:P53985 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ketoacidosis due to monocarboxylate transporter-1 deficiency (Moderate), mode of inheritance: Semidominant
• exercise-induced hyperinsulinism (Supportive), mode of inheritance: AD
• ketoacidosis due to monocarboxylate transporter-1 deficiency (Supportive), mode of inheritance: AD
• ketoacidosis due to monocarboxylate transporter-1 deficiency (Strong), mode of inheritance: AR
• metabolic myopathy due to lactate transporter defect (Limited), mode of inheritance: Unknown
• exercise-induced hyperinsulinism (Limited), mode of inheritance: Unknown
• ketoacidosis due to monocarboxylate transporter-1 deficiency (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperinsulinemic hypoglycemia, familial, 7; Erythrocyte lactate transporter defect; Monocarboxylate transporter 1 deficiency	AD/AR	Biochemical; Endocrine; Musculoskeletal; Renal	In Hyperinsulinemic hypoglycemia, familial, several affected individuals have reported as manifesting with severe sequelae, such as hypoglycemia-induced seizures, which could potentially be averted by early recognition and treatment; In Erythrocyte lactate transporter defect, exercise and heat exposure may result in sequelae such as rhabdomyolysis, and precautions may be beneficial; In Monocarboxylate transporter 1 deficiency, ensuring adequate caloric intake has been reported as beneficial to decrease the frequency of episodes of ketoacidotic episodes, and medical management (eg, with intravenous glucose or dextrose and bicarbonate) of episodes has been described as effective in terms of immediate management, and related long-term sequelae	Biochemical; Endocrine; Musculoskeletal; Neurologic; Renal	3775384; 3395513; 3395514; 1358043; 10590411; 11207177; 12502513; 17701893; 25390740; 25865495
Depending on the allelic condition, manifestations in dominant conditions may involve primarily endocrine or musculoskeletal/renal manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC16A1 gene.

• not provided (132 variants)
• Exercise-induced hyperinsulinism (60 variants)
• not specified (20 variants)
• Hyperinsulinism, Dominant (9 variants)
• Inborn genetic diseases (8 variants)
• Ketoacidosis due to monocarboxylate transporter-1 deficiency (6 variants)
• Metabolic myopathy due to lactate transporter defect (5 variants)
• Monocarboxylate transporter 1 deficiency, autosomal dominant (3 variants)
• SLC16A1-related condition (3 variants)
• Monocarboxylate transporter 1 deficiency, autosomal recessive (3 variants)
• SLC16A1-Related Disorders (2 variants)
• Metabolic myopathy due to lactate transporter defect;Exercise-induced hyperinsulinism;Ketoacidosis due to monocarboxylate transporter-1 deficiency (1 variants)
• Exercise-induced hyperinsulinism;Metabolic myopathy due to lactate transporter defect;Ketoacidosis due to monocarboxylate transporter-1 deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC16A1 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			4	31	1	36
missense			72	6	1	79
nonsense	4	2	1			7
start loss						0
frameshift	3	4	1			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding			35	19	8	62
Total	7	6	114	56	10

Highest pathogenic variant AF is 0.00000657

Variants in SLC16A1

This is a list of pathogenic ClinVar variants found in the SLC16A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-112911949-A-G		Exercise-induced hyperinsulinism	Benign (Jan 12, 2018)
1-112912015-C-G		Exercise-induced hyperinsulinism	Likely benign (Jan 13, 2018)
1-112912090-T-C		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112912237-T-C		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112912267-T-C		Exercise-induced hyperinsulinism	Likely benign (Jan 12, 2018)
1-112912477-G-A		Exercise-induced hyperinsulinism	Benign (Jan 13, 2018)
1-112912579-C-G		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112912610-A-C		Exercise-induced hyperinsulinism	Likely benign (Jan 13, 2018)
1-112912757-C-T		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112912805-TA-T		Hyperinsulinism, Dominant	Uncertain significance (Jun 14, 2016)
1-112912805-T-TA		Hyperinsulinism, Dominant	Uncertain significance (Jun 14, 2016)
1-112912819-C-A		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112912820-A-G		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112912827-C-A		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112912840-C-T		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112912847-A-C		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112912873-A-C		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112912921-G-GA		Hyperinsulinism, Dominant	Uncertain significance (Jun 14, 2016)
1-112912943-C-T		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112912945-C-T		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112913076-C-T		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112913152-A-C		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)
1-112913152-A-G		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112913234-G-T		Exercise-induced hyperinsulinism	Uncertain significance (Jan 12, 2018)
1-112913262-G-A		Exercise-induced hyperinsulinism	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC16A1	protein_coding	protein_coding	ENST00000538576	4	45167

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000736	0.983	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	193	269	0.716	0.0000138	3238
Missense in Polyphen		32	87.179	0.36706		1022
Synonymous	-1.09	118	104	1.14	0.00000593	1038
Loss of Function	2.12	8	17.6	0.455	0.00000117	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000354	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bodies. Required for normal nutrient assimilation, increase of white adipose tissue and body weight gain when on a high-fat diet. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate, small molecules that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis. {ECO:0000269|PubMed:17701893}.
• Disease: DISEASE: Familial hyperinsulinemic hypoglycemia 7 (HHF7) [MIM:610021]: Dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load. {ECO:0000269|PubMed:17701893}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Monocarboxylate transporter 1 deficiency (MCT1D) [MIM:616095]: A metabolic disorder characterized by recurrent ketoacidosis, a pathologic state due to ketone formation exceeding ketone utilization. The clinical consequences of ketoacidosis are vomiting, osmotic diuresis, dehydration, and Kussmaul breathing. The condition may progress to decreased consciousness and, ultimately, death. {ECO:0000269|PubMed:25390740}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Warburg Effect;Glutaminolysis and Cancer;Photodynamic therapy-induced HIF-1 survival signaling;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Bile salt and organic anion SLC transporters;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;Proton-coupled monocarboxylate transport;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Valine, leucine and isoleucine degradation;Butanoate metabolism;Vitamin E metabolism;Vitamin H (biotin) metabolism;Cell surface interactions at the vascular wall;Hemostasis;Basigin interactions;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.173
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.35

Haploinsufficiency Scores

• pHI: 0.258
• hipred: Y
• hipred_score: 0.789
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.901

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc16a1
• Phenotype: digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: pyruvate metabolic process;lipid metabolic process;centrosome cycle;monocarboxylic acid transport;mevalonate transport;response to food;plasma membrane lactate transport;glucose homeostasis;regulation of insulin secretion;leukocyte migration;behavioral response to nutrient;cellular response to organic cyclic compound
• Cellular component: centrosome;plasma membrane;integral component of plasma membrane;membrane;integral component of membrane;cell junction;intracellular membrane-bounded organelle;synapse;extracellular exosome
• Molecular function: monocarboxylic acid transmembrane transporter activity;lactate transmembrane transporter activity;mevalonate transmembrane transporter activity;symporter activity;protein homodimerization activity;organic cyclic compound binding