SLC44A1

Summary

SLC44A1 (solute carrier family 44 member 1, HGNC:18798) is a protein-coding gene on chromosome 9q31.1-q31.2, encoding Choline transporter-like protein 1 (Q8WWI5). Choline/H+ antiporter.

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.

Source: NCBI Gene 23446 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 130 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_080546

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18798
Approved symbol	SLC44A1
Name	solute carrier family 44 member 1
Location	9q31.1-q31.2
Locus type	gene with protein product
Status	Approved
Aliases	CTL1, CHTL1, CD92
Ensembl gene	ENSG00000070214
Ensembl biotype	protein_coding
OMIM	606105
Entrez	23446

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000374720, ENST00000374723, ENST00000374724, ENST00000436716, ENST00000470972, ENST00000607692, ENST00000607701, ENST00000699289, ENST00000699290, ENST00000886928, ENST00000886929, ENST00000886930, ENST00000886931, ENST00000886932, ENST00000912408, ENST00000912409, ENST00000912410, ENST00000912411, ENST00000970463

RefSeq mRNA: 3 — MANE Select: NM_080546 NM_001286730, NM_001330731, NM_080546

CCDS: CCDS6763, CCDS75868, CCDS83390

Canonical transcript exons

ENST00000374720 — 16 exons

Exon	Start	End
ENSE00000805932	105383123	105383359
ENSE00000805933	105385422	105385502
ENSE00000926752	105374598	105374735
ENSE00000926753	105366346	105366429
ENSE00000926754	105365483	105365639
ENSE00000926755	105364555	105364720
ENSE00000926756	105362821	105363007
ENSE00000926757	105361191	105361330
ENSE00000926758	105358344	105358433
ENSE00000926759	105356212	105356381
ENSE00000926760	105348358	105348451
ENSE00000926761	105335563	105335699
ENSE00000983364	105309724	105309866
ENSE00001742967	105299220	105299309
ENSE00001818998	105389033	105397346
ENSE00003847051	105244651	105244904

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.8162 / max 1310.6865, expressed in 1766 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97817	46.8893	1766
97818	0.7397	327
97822	0.1147	45
97821	0.0724	43

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.72	gold quality
inferior vagus X ganglion	UBERON:0005363	99.72	gold quality
medial globus pallidus	UBERON:0002477	99.49	gold quality
globus pallidus	UBERON:0001875	99.46	gold quality
subthalamic nucleus	UBERON:0001906	99.28	gold quality
superior vestibular nucleus	UBERON:0007227	99.22	gold quality
lateral globus pallidus	UBERON:0002476	99.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.18	gold quality
ventral tegmental area	UBERON:0002691	99.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.05	gold quality
corpus epididymis	UBERON:0004359	99.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.95	gold quality
corpus callosum	UBERON:0002336	98.92	gold quality
pons	UBERON:0000988	98.83	gold quality
colonic mucosa	UBERON:0000317	98.70	gold quality
substantia nigra pars compacta	UBERON:0001965	98.57	gold quality
spinal cord	UBERON:0002240	98.42	gold quality
penis	UBERON:0000989	98.07	gold quality
gingiva	UBERON:0001828	98.03	gold quality
mammalian vulva	UBERON:0000997	98.01	gold quality
gingival epithelium	UBERON:0001949	97.94	gold quality
seminal vesicle	UBERON:0000998	97.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.16	gold quality
upper leg skin	UBERON:0004262	97.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.92	gold quality
tibia	UBERON:0000979	96.87	gold quality
pylorus	UBERON:0001166	96.80	gold quality
skin of hip	UBERON:0001554	96.67	gold quality
trabecular bone tissue	UBERON:0002483	96.65	gold quality
nipple	UBERON:0002030	96.53	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	3559.11
E-GEOD-89232	yes	420.24
E-HCAD-25	yes	77.58
E-GEOD-84465	yes	13.73
E-MTAB-9067	yes	11.74
E-MTAB-8142	yes	10.91
E-MTAB-10553	yes	8.82
E-GEOD-93593	yes	6.51
E-GEOD-180759	no	2939.66
E-CURD-10	no	293.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

357 targeting SLC44A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-103A-3P	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 20)

• This study provides the first example of CHT1 expression in neurons which do not use acetylcholine as neurotransmitter. (PMID:15691711)
• Data suggest that an impaired choline transporter-like protein-1 trafficking is the key contributing factor to reduced choline uptake, subsequent to the PMA-induced THP-1 differentiation to macrophages. (PMID:16319125)
• characterization the 5’-flanking region of the human (h)CTL1 gene and some of the possible mechanisms of its regulation, including promoter activity, splicing, and expression (PMID:16609143)
• SLC44A1 mRNA and protein expression were down-regulated during choline deficiency. (PMID:19357133)
• The presence of CTL1 protein in rat and human CNS regions, where it is found in neuronal, glial and endothelial cells, suggests that malfunction of this transporter could have important implications in nervous system development and repair. (PMID:19519661)
• In conclusion, choline transport in A549 cells is increased by treatment with DEX, and the increase is mediated by induction of functional choline transporters CTL1 and CTL2. (PMID:20410607)
• CTL1 is expressed in both SH-SY5Y and LA-N-2 cells and is responsible for choline uptake that relies on a directed hydrogen ion gradient as a driving force. (PMID:21185344)
• REVIEW highlights discovery and characterization of SLC44A1, describes its expression patterns and subcellular localization and summarizes evidence for the role of this choline transporter in the central nervous system. (PMID:22483272)
• NCI-H69 cells express the choline transporter CTL1 which uses a directed H(+) gradient as a driving force, and its transport functions in co-operation with NHE1. (PMID:23948665)
• Reduced CTL1 expression is associated with postural orthostatic tachycardia syndrome. (PMID:25466896)
• The differential expression pattern of CTL1 and CTL2 suggests that CTL1 is the key transporter involved in choline transport from maternal circulation and both transporters are likely involved in stromal and endothelial cell choline transport. (PMID:26601765)
• This study showed that SLC44A1-PRKCA fusion seems to be a specific characteristic of Papillary glioneuronal tumors with a high diagnostic value. (PMID:26671581)
• SLC44A1 and KLF13 may be involved in tumorigenesis and the metastasis of colon cancer by miRNA regulation (PMID:29408621)
• SLC44A1 acts as a choline transporter both in the plasma membrane and in the mitochondria. Novel aspects of choline transport regulation in the muscle, nervous system, and cancer are reviewed. Review. (PMID:30776907)
• Study of genome-wide epigenetic changes in bronchial epithelial cells of asthmatic patients, following cells treatment with vitamin D3 and Poly (I:C)(a viral analogue) allows the identification of biologically plausible candidate genes for viral infections and asthma, such as DUSP10 and SLC44A1. (PMID:31122150)
• Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (PMID:31855247)
• Protein kinase C promotes choline transporterlike protein 1 function via improved cell surface expression in immortalized human hepatic cells. (PMID:31974614)
• Functional Expression of Choline Transporters in Human Neural Stem Cells and Its Link to Cell Proliferation, Cell Viability, and Neurite Outgrowth. (PMID:33672580)
• Choline transporter-like proteins 1 and 2 are newly identified plasma membrane and mitochondrial ethanolamine transporters. (PMID:33789160)
• Polymorphisms in the choline transporter SLC44A1 are associated with reduced cognitive performance in normotypic but not prenatal alcohol-exposed children. (PMID:38176775)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc44a1b	ENSDARG00000090982
mus_musculus	Slc44a1	ENSMUSG00000028412
rattus_norvegicus	Slc44a1	ENSRNOG00000055089

Paralogs (4): SLC44A2 (ENSG00000129353), SLC44A5 (ENSG00000137968), SLC44A3 (ENSG00000143036), SLC44A4 (ENSG00000204385)

Protein

Protein identifiers

Choline transporter-like protein 1 — Q8WWI5 (reviewed: Q8WWI5)

Alternative names: CDw92, Solute carrier family 44 member 1

All UniProt accessions (3): Q8WWI5, A0A8V8TN05, A0A8V8TN34

UniProt curated annotations — full annotation on UniProt →

Function. Choline/H+ antiporter. Also acts as a high-affinity ethanolamine/H+ antiporter, regulating the supply of extracellular ethanolamine (Etn) for the CDP-Etn pathway, redistribute intracellular Etn and balance the CDP-Cho and CDP-Etn arms of the Kennedy pathway. Involved in membrane synthesis and myelin production.

Subcellular location. Cell membrane. Mitochondrion outer membrane.

Tissue specificity. Expressed in various cells of the hematopoietic system.

Disease relevance. Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline (CONATOC) [MIM:618868] An autosomal recessive neurodegenerative disease characterized by progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrates cerebellar atrophy and leukoencephalopathy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CTL (choline transporter-like) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WWI5-1	1, A	yes
Q8WWI5-2	2, B
Q8WWI5-3	3, C

RefSeq proteins (3): NP_001273659, NP_001317660, NP_536856* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007603	Choline_transptr-like	Family

Pfam: PF04515

Catalyzed reactions (Rhea), 2 shown:

• choline(out) + n H(+)(in) = choline(in) + n H(+)(out) (RHEA:75463)
• ethanolamine(out) + n H(+)(in) = ethanolamine(in) + n H(+)(out) (RHEA:75467)

UniProt features (31 total): topological domain 10, transmembrane region 9, splice variant 4, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9QU3	ELECTRON MICROSCOPY	3.2
7WWB	ELECTRON MICROSCOPY	3.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWI5-F1	83.74	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 652, 2

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1483191	Synthesis of PC
R-HSA-6798163	Choline catabolism
R-HSA-9958517	SLC-mediated bile acid transport
R-HSA-425366

MSigDB gene sets: 518 (showing top): CREL_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GCANCTGNY_MYOD_Q6, AREB6_03, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AREB6_01, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CAGGTCC_MIR492, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, FOXD3_01

GO Biological Process (6): phosphatidylcholine biosynthetic process (GO:0006656), choline transport (GO:0015871), ethanolamine transport (GO:0034229), choline catabolic process (GO:0042426), transmembrane transport (GO:0055085), transport across blood-brain barrier (GO:0150104)

GO Molecular Function (4): choline transmembrane transporter activity (GO:0015220), antiporter activity (GO:0015297), ethanolamine transmembrane transporter activity (GO:0034228), transmembrane transporter activity (GO:0022857)

GO Cellular Component (7): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Metabolism of amino acids and derivatives	1
SLC-mediated transport of organic anions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
phosphatidylcholine metabolic process	1
glycerophospholipid biosynthetic process	1
nitrogen compound transport	1
amine transport	1
organic hydroxy compound transport	1
choline metabolic process	1
biogenic amine catabolic process	1
transport	1
cellular process	1
vascular transport	1
choline transport	1
transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
amine transmembrane transporter activity	1
alcohol transmembrane transporter activity	1
ethanolamine transport	1
transporter activity	1
transmembrane transport	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC44A1	SLC5A7	Q9GZV3	693
SLC44A1	CHKA	P35790	482
SLC44A1	SLC41A1	Q8IVJ1	478
SLC44A1	CADM4	Q8NFZ8	474
SLC44A1	CHKB	Q9Y259	438
SLC44A1	LRRC8B	Q6P9F7	433
SLC44A1	HOOK3	Q86VS8	432
SLC44A1	SLC7A2	P52569	429
SLC44A1	PRRG1	O14668	420
SLC44A1	SCAMP1	O15126	420
SLC44A1	TBC1D15	Q8TC07	419
SLC44A1	HOOK1	Q9UJC3	412
SLC44A1	SLC22A4	Q9H015	410
SLC44A1	RAB9A	P51151	406
SLC44A1	SPNS1	Q9H2V7	400

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LRRC8B	SLC25A17	psi-mi:“MI:0914”(association)	0.530
SMAP	SLC44A1	psi-mi:“MI:0915”(physical association)	0.370
SLC44A1	KCNE3	psi-mi:“MI:0915”(physical association)	0.370
NUDT21	SLC44A1	psi-mi:“MI:0915”(physical association)	0.370
ADAM10	TSPAN9	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
KCNMB3	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
NKAIN1	GPR89A	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
CYB5B	QSOX1	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
CYB561D2	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
OR10H1	NRP1	psi-mi:“MI:0914”(association)	0.350
LYPD3	TNPO2	psi-mi:“MI:0914”(association)	0.350
NT5E	SCAMP3	psi-mi:“MI:0914”(association)	0.350
TMEM128	PLSCR1	psi-mi:“MI:0914”(association)	0.350
SLC31A2	PLSCR1	psi-mi:“MI:0914”(association)	0.350
LDAF1	SLC19A2	psi-mi:“MI:0914”(association)	0.350
KCNK7	SLC44A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (240): SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-RNA), SLC44A1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-RNA), SLC44A1 (Proximity Label-MS)

ESM2 similar proteins: A3KMY4, A5D7H3, A5PF08, A5PMW0, B0JZD0, B0S5A7, B4F795, B5TYT3, B5X3W7, F1S584, O54902, P04839, P49282, P52649, P58421, Q3MHV9, Q53GD3, Q5R419, Q5R5L9, Q5XEZ5, Q66IV3, Q68EQ9, Q6AY92, Q6DHB5, Q6DHU1, Q6GN42, Q6INE8, Q6IP59, Q6IR74, Q6MG71, Q6X893, Q7SYC9, Q7T2B0, Q7TNK0, Q810F1, Q8BY89, Q8IWA5, Q8NCS7, Q8VII6, Q8VZM5

Diamond homologs: A5PK40, Q17JQ7, Q6AY92, Q6GN42, Q6IP59, Q6IR74, Q6X893, Q7PRJ0, Q7Q5R7, Q7SYC9, Q810F1, Q8N4M1, Q8VII6, Q8WWI5, Q921V7, Q9I9B9, Q9VAP3, Q9VZE7, A3KMY4, A5D7H3, A5PF08, A5PMW0, A8XKF2, B0JZD0, B0S5A7, B4F795, B5X3W7, F1S584, Q20026, Q4I8E9, Q53GD3, Q5R5L9, Q5RJI2, Q6C938, Q6MG71, Q7T2B0, Q869R1, Q8BY89, Q8IWA5, Q8NCS7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

130 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	86
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1705625	NM_080546.5(SLC44A1):c.588del (p.Ser196fs)	Pathogenic
848628	NM_080546.5(SLC44A1):c.1053C>G (p.Tyr351Ter)	Pathogenic
870502	NM_080546.5(SLC44A1):c.1549del (p.Asp517fs)	Pathogenic
870503	NM_080546.5(SLC44A1):c.377_380del (p.Ser126fs)	Pathogenic
870504	NM_080546.5:c.126+5161_270-2343del	Pathogenic
804415	NM_080546.5(SLC44A1):c.1009C>T (p.Gln337Ter)	Likely pathogenic

SpliceAI

3766 predictions. Top by Δscore:

Variant	Effect	Δscore
9:105299208:A:AG	acceptor_gain	1.0000
9:105299209:T:G	acceptor_gain	1.0000
9:105299214:A:AG	acceptor_gain	1.0000
9:105299215:A:G	acceptor_gain	1.0000
9:105299218:A:AG	acceptor_gain	1.0000
9:105299219:G:GA	acceptor_gain	1.0000
9:105299219:G:GT	acceptor_loss	1.0000
9:105299219:GA:G	acceptor_gain	1.0000
9:105299219:GAGCT:G	acceptor_gain	1.0000
9:105299305:GGATG:G	donor_gain	1.0000
9:105299306:GATG:G	donor_gain	1.0000
9:105299306:GATGG:G	donor_gain	1.0000
9:105309863:GGAA:G	donor_gain	1.0000
9:105309864:G:GT	donor_gain	1.0000
9:105309864:GAA:G	donor_gain	1.0000
9:105309867:G:GG	donor_gain	1.0000
9:105348356:A:AG	acceptor_gain	1.0000
9:105348356:A:G	acceptor_loss	1.0000
9:105348357:G:GC	acceptor_loss	1.0000
9:105348357:G:GG	acceptor_gain	1.0000
9:105348447:GCGAG:G	donor_gain	1.0000
9:105348448:CGAG:C	donor_loss	1.0000
9:105348450:AGG:A	donor_loss	1.0000
9:105348451:GG:G	donor_loss	1.0000
9:105348452:GTAA:G	donor_loss	1.0000
9:105356210:A:AG	acceptor_gain	1.0000
9:105356211:G:GA	acceptor_gain	1.0000
9:105358342:A:AG	acceptor_gain	1.0000
9:105358343:G:GG	acceptor_gain	1.0000
9:105358343:GTT:G	acceptor_gain	1.0000

AlphaMissense

4298 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:105335630:T:A	C113S	1.000
9:105335631:G:C	C113S	1.000
9:105335632:T:G	C113W	1.000
9:105364647:T:A	W394R	1.000
9:105364647:T:C	W394R	1.000
9:105309784:G:C	D63H	0.999
9:105309785:A:T	D63V	0.999
9:105309802:T:A	C69S	0.999
9:105309802:T:C	C69R	0.999
9:105309803:G:A	C69Y	0.999
9:105309803:G:C	C69S	0.999
9:105309803:G:T	C69F	0.999
9:105309804:T:G	C69W	0.999
9:105335630:T:C	C113R	0.999
9:105335631:G:A	C113Y	0.999
9:105335631:G:T	C113F	0.999
9:105335642:T:A	C117S	0.999
9:105335642:T:C	C117R	0.999
9:105335643:G:C	C117S	0.999
9:105348371:T:G	C140W	0.999
9:105356235:G:C	R175P	0.999
9:105356237:T:A	C176S	0.999
9:105356237:T:C	C176R	0.999
9:105356238:G:A	C176Y	0.999
9:105356238:G:C	C176S	0.999
9:105356239:T:G	C176W	0.999
9:105361208:T:A	W260R	0.999
9:105361208:T:C	W260R	0.999
9:105364638:G:C	G391R	0.999
9:105364639:G:A	G391D	0.999

dbSNP variants (sampled 300 via entrez): RS1000005131 (9:105243218 T>C), RS1000014398 (9:105433657 C>A), RS1000015443 (9:105244198 T>C), RS1000018002 (9:105375034 TG>T), RS1000032705 (9:105409264 T>C), RS1000034634 (9:105284904 A>C), RS1000065255 (9:105415117 GTTA>G), RS1000066418 (9:105328279 G>A), RS1000084732 (9:105421711 C>T), RS1000084833 (9:105373756 C>T), RS1000088434 (9:105415925 A>G,T), RS1000097252 (9:105328537 G>A), RS1000103263 (9:105248643 T>G), RS1000118917 (9:105372437 G>A), RS1000127820 (9:105391907 C>A,T)

Disease associations

OMIM: gene MIM:606105 | disease phenotypes: MIM:618868

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline	Strong	Autosomal recessive

Mondo (2): neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline (MONDO:0030028), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000486	Strabismus
HP:0000514	Slow saccadic eye movements
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0002015	Dysphagia
HP:0002073	Progressive cerebellar ataxia
HP:0002169	Clonus
HP:0002353	EEG abnormality
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002607	Bowel incontinence
HP:0003487	Babinski sign
HP:0006579	Prolonged neonatal jaundice
HP:0033048	Substantia nigra hypointensity on susceptibility-weighted imaging
HP:0033049	Globus pallidus hypointensity on susceptibility-weighted imaging

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000404_1	Menarche (age at onset)	2.000000e-09
GCST002863_2	Behavioral disturbance or psychiatric symptoms in prion disease	6.000000e-06
GCST002931_4	Aluminium levels	9.000000e-06
GCST003487_1	Response to fenofibrate (total cholesterol levels)	7.000000e-06
GCST004749_27	Lung cancer in ever smokers	7.000000e-07
GCST005580_130	Intraocular pressure	3.000000e-49
GCST005580_226	Intraocular pressure	7.000000e-19
GCST007998_4	Intraocular pressure	4.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007806	total cholesterol change measurement
EFO:0004695	intraocular pressure measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066446 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC44 choline transporter-like family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
hemicholinium-3	Inhibition	4.5	pKi

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	5
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	decreases expression, decreases methylation, increases expression, decreases reaction, increases abundance (+1 more)	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression, affects cotreatment, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
deoxynivalenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652471	Binding	Binding affinity to human SLC44A1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2GA	Abcam HeLa SLC44A1 KO	Cancer cell line	Female
CVCL_D4P4	HCT116-SLC44A1-KO-c14	Cancer cell line	Male
CVCL_D4P5	HCT116-SLC44A1-KO-c32	Cancer cell line	Male
CVCL_TN75	HAP1 SLC44A1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice