SLC44A1

Chr 9AR

solute carrier family 44 member 1

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

NCBI Gene: 23446 ENSG00000070214 UniProt: Q8WWI5 OMIM: 606105

This protein functions as a choline/proton antiporter and high-affinity ethanolamine/proton antiporter, playing a critical role in membrane synthesis and myelin production. Mutations cause autosomal recessive neurodegeneration with childhood onset, characterized by ataxia, tremor, optic atrophy, and cognitive decline. The gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.265), indicating that functional copies are essential for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.271 OMIM phenotype

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

6 unique Pathogenic / Likely Pathogenic· 90 VUS of 135 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.73Z-score

OE missense 0.74 (0.67–0.82)

260 obs / 351.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.06–0.27)

0≤0.351.4

Missense OE?0.74 (0.67–0.82)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

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

This gene — mechanism propensity

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.

LOF83% of P/LP variants are LoF · LOEUF 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.

ClinVar Variant Classifications

135 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic1

VUS90

Likely Benign10

Benign8

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	1	0	5
Likely Pathogenic	1	0	0	0	1
VUS	0	90	0	0	90
Likely Benign	0	3	0	7	10
Benign	0	2	4	2	8
Conflicting	—				1
Total	5	95	5	9	115

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

37 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap SLC44A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →