SLC5A7

solute carrier family 5 member 7, the group of Solute carrier family 5

Basic information

Region (hg38): 2:107986523-108013994

Links

ENSG00000115665 ∙ NCBI:60482 ∙ OMIM:608761 ∙ HGNC:14025 ∙ Uniprot:Q9GZV3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 20 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 20 (Strong), mode of inheritance: AR
• neuronopathy, distal hereditary motor, type 7A (Moderate), mode of inheritance: AD
• congenital myasthenic syndrome 20 (Strong), mode of inheritance: AR
• presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD
• distal hereditary motor neuropathy type 7 (Supportive), mode of inheritance: AD
• congenital myasthenic syndrome 20 (Strong), mode of inheritance: AR
• neuronopathy, distal hereditary motor, type 7A (Strong), mode of inheritance: AD
• neuronopathy, distal hereditary motor, type 7A (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 20, presynaptic	AR	Neurologic	The condition involves muscular weakness, and medical managament (with AChE inhibitors) has been described as beneficial in some individuals	Neurologic	11294660; 23141292; 27569547

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC5A7 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC5A7 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			2	115		117
missense		1	225	2	1	229
nonsense			6			6
start loss						0
frameshift		3	4			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	4			6
splice region			8	11		19
non coding			2	55	19	76
Total	0	6	244	172	20

Variants in SLC5A7

This is a list of pathogenic ClinVar variants found in the SLC5A7 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-107987811-A-G			Benign (Oct 17, 2018)
2-107987955-T-C			Benign (Oct 17, 2018)
2-107987962-C-T			Benign (Oct 17, 2018)
2-107988163-T-C		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Uncertain significance (Aug 11, 2023)
2-107988165-C-G		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Oct 06, 2020)
2-107988167-T-G		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Uncertain significance (Nov 17, 2023)
2-107988168-G-A		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Aug 14, 2021)
2-107988174-G-C		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Uncertain significance (May 15, 2023)
2-107988176-A-G		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Likely benign (Dec 02, 2023)
2-107988180-A-G			Uncertain significance (Sep 12, 2022)
2-107988181-T-C		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Aug 17, 2023)
2-107988186-A-G		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20 • Inborn genetic diseases	Uncertain significance (Oct 08, 2022)
2-107988189-A-G		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Uncertain significance (Mar 12, 2023)
2-107988190-T-C		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Jun 04, 2022)
2-107988191-C-T		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Likely benign (May 17, 2023)
2-107988192-G-A		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Dec 19, 2020)
2-107988194-G-A		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Likely benign (Nov 17, 2023)
2-107988197-C-A		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Uncertain significance (May 22, 2018)
2-107988201-C-A		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Uncertain significance (Aug 04, 2023)
2-107988201-C-G		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Nov 06, 2020)
2-107988201-C-T		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20 • Inborn genetic diseases • SLC5A7-related disorder	Conflicting classifications of pathogenicity (Aug 27, 2024)
2-107988209-T-C		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A	Likely benign (Aug 17, 2023)
2-107988229-C-T		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Uncertain significance (Dec 14, 2021)
2-107988236-G-A		Congenital myasthenic syndrome 20;Neuronopathy, distal hereditary motor, type 7A • Inborn genetic diseases	Uncertain significance (Jul 07, 2023)
2-107988239-A-G		Neuronopathy, distal hereditary motor, type 7A;Congenital myasthenic syndrome 20	Likely benign (Nov 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC5A7	protein_coding	protein_coding	ENST00000264047	8	27472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0153	0.985	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.81	180	322	0.560	0.0000164	3729
Missense in Polyphen		32	100.52	0.31834		1163
Synonymous	-0.138	125	123	1.02	0.00000663	1213
Loss of Function	3.23	8	25.7	0.311	0.00000136	294

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000207	0.000207
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000881	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transmembrane transporter that imports choline from the extracellular space into the neuron with high affinity. Choline uptake is the rate-limiting step in acetylcholine synthesis. Sodium ion- and chloride ion-dependent. {ECO:0000269|PubMed:11027560, ECO:0000269|PubMed:27569547}.
• Disease: DISEASE: Neuronopathy, distal hereditary motor, 7A (HMN7A) [MIM:158580]: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN7A is characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve. {ECO:0000269|PubMed:23141292}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 20, presynaptic (CMS20) [MIM:617143]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS20 is an autosomal recessive, pre-synaptic form characterized by severe hypotonia and episodic apnea soon after birth, generalized limb fatigability and weakness, delayed walking, ptosis, poor sucking and swallowing. {ECO:0000269|PubMed:27569547}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Choline metabolism in cancer - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction);Nuclear Receptors Meta-Pathway;NRF2 pathway;Monoamine Transport;Amine compound SLC transporters;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Neuronal System;Glycerophospholipid metabolism;Acetylcholine Neurotransmitter Release Cycle;Neurotransmitter release cycle;Transmission across Chemical Synapses;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

• pRec: 0.214

Intolerance Scores

• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.37

Haploinsufficiency Scores

• pHI: 0.300
• hipred: Y
• hipred_score: 0.771

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc5a7
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: sodium ion transport;neurotransmitter secretion;synaptic transmission, cholinergic;neuromuscular synaptic transmission;acetylcholine biosynthetic process;choline transport;transmembrane transport
• Cellular component: plasma membrane;integral component of membrane;cell junction;axon;dendrite;neuromuscular junction;perikaryon;synapse;presynapse
• Molecular function: choline:sodium symporter activity;choline transmembrane transporter activity;choline binding