SLC5A7

Chr 2ARAD

solute carrier family 5 member 7

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismAR/ADLOEUF 0.562 OMIM phenotypes
Clinical SummarySLC5A7
🧬
Gene-Disease Validity (ClinGen)
neuronopathy, distal hereditary motor, type 7A · ADModerate

Moderate evidence — consider for supplementary testing

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.015
Z-score 3.23
OE 0.31 (0.180.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.81Z-score
OE missense 0.56 (0.490.63)
180 obs / 321.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.31 (0.180.56)
00.351.4
Missense OE0.56 (0.490.63)
00.61.4
Synonymous OE1.02
01.21.6
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

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

DN
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.PMID:29582019

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC5A7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →