SLC5A7

Chr 2ARAD

solute carrier family 5 member 7

Also known as: CHT, CHT1, CMS20, DHMNVP, HMN7A, HMND7, hCHT1

NCBI Gene: 60482 ENSG00000115665 UniProt: Q9GZV3 OMIM: 608761

This protein functions as a sodium- and chloride-dependent high-affinity choline transporter that mediates choline uptake into presynaptic cholinergic terminals for acetylcholine synthesis. Mutations cause congenital myasthenic syndrome type 20 (presynaptic) with autosomal recessive inheritance and distal hereditary motor neuronopathy type VIIA with autosomal dominant inheritance. The pathogenic mechanism involves gain-of-function effects that disrupt normal cholinergic neurotransmission.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia. An allelic variant of this gene is associated with autosomal dominant distal hereditary motor neuronopathy type VIIA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAR/ADLOEUF 0.562 OMIM phenotypes

Clinical Summary— SLC5A7

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Gene-Disease Validity (ClinGen)

neuronopathy, distal hereditary motor, type 7A · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.015

Z-score 3.23

OE 0.31 (0.18–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.81Z-score

OE missense 0.56 (0.49–0.63)

180 obs / 321.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.31 (0.18–0.56)

0≤0.351.4

Missense OE?0.56 (0.49–0.63)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 25.7Missense obs/exp: 180 / 321.6Syn Z: -0.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongSLC5A7-related congenital myasthenic syndrome with episodic apneaOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.79top 25%

GOF

0.80top 10%

LOF

0.2091th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNWe previously reported a dominant-negative frameshift mutation located in the concluding exon of the SLC5A7 gene encoding the choline transporter (CHT), leading to protein truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended UK family.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References