SLC44A1

Chr 9AR

solute carrier family 44 member 1

Also known as: CD92, CDW92, CHTL1, CONATOC, CTL1

NCBI Gene: 23446 ENSG00000070214 UniProt: Q8WWI5

Enables choline transmembrane transporter activity and ethanolamine transmembrane transporter activity. Involved in choline transport; ethanolamine transport; and transmembrane transport. Located in several cellular components, including cytosol; mitochondrial outer membrane; and nucleoplasm. Implicated in high grade glioma. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive declineMIM #618868

Active trials

Pathogenic / LP

155

ClinVar variants

Pubs (1 yr)

1.7

Missense Z

0.27

LOEUF· LoF intolerant

Clinical Summary— SLC44A1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

42 Pathogenic / Likely Pathogenic· 94 VUS of 155 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.27LOEUF

pLI 0.997

Z-score 4.81

OE 0.12 (0.06–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.73Z-score

OE missense 0.74 (0.67–0.82)

260 obs / 351.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.06–0.27)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.67–0.82)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96

0≤1.21.6

LoF obs/exp: 4 / 34.5Missense obs/exp: 260 / 351.3Syn Z: 0.38

0.4983th %ile

GOF

0.76top 25%

LOF

0.4627th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.27

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.