SLCO1C1

Summary

SLCO1C1 (solute carrier organic anion transporter family member 1C1, HGNC:13819) is a protein-coding gene on chromosome 12p12.2, encoding Solute carrier organic anion transporter family member 1C1 (Q9NYB5). Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3’,5’-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane.

This gene encodes a member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of thyroid hormones in brain tissues. This protein has particularly high affinity for the thyroid hormones thyroxine, tri-iodothyronine and reverse tri-iodothyronine. Polymorphisms in the gene encoding this protein may be associated with fatigue and depression in patients suffering from hyperthyroidism. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 53919 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 96 total
• Druggable target: yes
• MANE Select transcript: NM_017435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13819
Approved symbol	SLCO1C1
Name	solute carrier organic anion transporter family member 1C1
Location	12p12.2
Locus type	gene with protein product
Status	Approved
Aliases	OATP-F, OATP1C1, OATP1
Ensembl gene	ENSG00000139155
Ensembl biotype	protein_coding
OMIM	613389
Entrez	53919

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000266509, ENST00000497911, ENST00000534996, ENST00000535609, ENST00000539415, ENST00000539443, ENST00000540354, ENST00000545102, ENST00000545604, ENST00000947229

RefSeq mRNA: 4 — MANE Select: NM_017435 NM_001145944, NM_001145945, NM_001145946, NM_017435

CCDS: CCDS53757, CCDS53758, CCDS53759, CCDS8683

Canonical transcript exons

ENST00000266509 — 15 exons

Exon	Start	End
ENSE00000936701	20701318	20701459
ENSE00000994840	20695332	20695807
ENSE00001246638	20750675	20750792
ENSE00001246734	20699552	20699705
ENSE00001669770	20752306	20753386
ENSE00003497378	20715139	20715285
ENSE00003504241	20721804	20722049
ENSE00003513061	20705949	20706081
ENSE00003528084	20723090	20723254
ENSE00003544471	20737107	20737272
ENSE00003568614	20732909	20733104
ENSE00003588867	20743305	20743369
ENSE00003601499	20711386	20711510
ENSE00003612416	20717132	20717230
ENSE00003670181	20740184	20740368

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 97.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8982 / max 143.5361, expressed in 198 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124648	0.5002	102
124646	0.4513	109
124643	0.2336	118
124649	0.2017	85
124645	0.1658	82
124642	0.1329	83
124641	0.1050	54
124647	0.0729	55
124644	0.0347	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	97.96	gold quality
endothelial cell	CL:0000115	93.19	gold quality
ventricular zone	UBERON:0003053	91.16	gold quality
CA1 field of hippocampus	UBERON:0003881	90.48	gold quality
ganglionic eminence	UBERON:0004023	88.97	gold quality
caudate nucleus	UBERON:0001873	88.95	gold quality
putamen	UBERON:0001874	87.79	gold quality
nucleus accumbens	UBERON:0001882	86.09	gold quality
entorhinal cortex	UBERON:0002728	85.93	gold quality
amygdala	UBERON:0001876	85.04	gold quality
temporal lobe	UBERON:0001871	84.73	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.48	gold quality
anterior cingulate cortex	UBERON:0009835	83.45	gold quality
cranial nerve II	UBERON:0000941	83.38	gold quality
cingulate cortex	UBERON:0003027	83.34	gold quality
superior frontal gyrus	UBERON:0002661	83.15	gold quality
right frontal lobe	UBERON:0002810	83.11	gold quality
telencephalon	UBERON:0001893	82.94	gold quality
Ammon’s horn	UBERON:0001954	82.65	gold quality
primary visual cortex	UBERON:0002436	82.49	gold quality
postcentral gyrus	UBERON:0002581	82.28	gold quality
cerebral cortex	UBERON:0000956	81.58	gold quality
neocortex	UBERON:0001950	81.19	gold quality
frontal cortex	UBERON:0001870	81.00	gold quality
prefrontal cortex	UBERON:0000451	80.49	gold quality
forebrain	UBERON:0001890	80.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.71	gold quality
occipital lobe	UBERON:0002021	79.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	10.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

65 targeting SLCO1C1, 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-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4677-5P	99.70	70.09	1940

Literature-anchored findings (GeneRIF, showing 15)

• We have isolated and functionally characterized OATP-F. OATP-F has a more selective substrate preference and may play an important role in the disposition of thyroid hormones in brain and testis. (PMID:12351693)
• OATP1C1 polymorphisms are associated with fatigue and depression, but do not explain differences in neurocognitive functioning or appreciation of LT4-LT3 combination therapy. (PMID:18410547)
• OATP1C1 mediates transport of thyroid hormones and increases the access of these substrates to the intracellular active sites of the deiodinases with no effect of genetic variation (PMID:18566113)
• OATP14 mRNA and protein are strongly enriched in mouse and rat cerebral microvessels but not in human microvessels. (PMID:18687783)
• Protein is highly expressed in the intestine, kidney, cholangiocytes and the blood-brain barrier. (PMID:19290786)
• Compared with the adult cerebral cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. (PMID:21486766)
• The strong expression of MCT10 and OATP1C1 in the human hypothalamus indicates a possible role in the regulation of the hypothalamus-pituitary-thyroid axis. (PMID:21508134)
• The PDE3A-SLCO1C1 locus rs3794271 SNP showed a highly significant association with anti-TNF treatment response. (PMID:23651021)
• We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (PMID:25403996)
• The genetic variant, rs3794271, located within the PDE3A-SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria and absolute change in (Delta)DAS28 scores as outcome measures correlated with anti-TNF response in a large UK rheumatoid arthritis cohort. (PMID:27180831)
• Deiodinases, organic anion transporter polypeptide polymorphisms and ischemic stroke outcomes. (PMID:31677555)
• Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke. (PMID:32807452)
• Single nucleotide polymorphisms in ADAM17, IL23R and SLCO1C1 genes protect against infliximab failure in adults with Crohn’s disease. (PMID:36621146)
• Thyroid Hormone Transporters MCT8 and OATP1C1 Are Expressed in Pyramidal Neurons and Interneurons in the Adult Motor Cortex of Human and Macaque Brain. (PMID:36834621)
• Thyroid Hormone Transporters MCT8 and OATP1C1 Are Expressed in Projection Neurons and Interneurons of Basal Ganglia and Motor Thalamus in the Adult Human and Macaque Brains. (PMID:37298594)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slco1c1	ENSDARG00000016749
mus_musculus	Slco1c1	ENSMUSG00000030235
rattus_norvegicus	Slco1c1	ENSRNOG00000009740
drosophila_melanogaster	Oatp30B	FBGN0032123

Paralogs (10): SLCO1A2 (ENSG00000084453), SLCO4A1 (ENSG00000101187), SLCO1B3 (ENSG00000111700), SLCO1B1 (ENSG00000134538), SLCO2B1 (ENSG00000137491), SLCO5A1 (ENSG00000137571), SLCO4C1 (ENSG00000173930), SLCO2A1 (ENSG00000174640), SLCO3A1 (ENSG00000176463), SLCO6A1 (ENSG00000205359)

Protein

Protein identifiers

Solute carrier organic anion transporter family member 1C1 — Q9NYB5 (reviewed: Q9NYB5)

Alternative names: Organic anion transporter 1C1, Organic anion transporter F, Organic anion transporter polypeptide-related protein 5, Organic anion-transporting polypeptide 14, Solute carrier family 21 member 14, Thyroxine transporter

All UniProt accessions (2): Q9NYB5, F5H6S4

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3’,5’-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane. Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases. Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency. Transports T4 and E1S in a pH-insensitive manner. Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in brain and in Leydig cells in testis. Localized in nests of Leydig cells (at protein level). Expressed in choroid plexus (at protein level). Not strongly enriched in cerebral microvessels.

Similarity. Belongs to the organo anion transporter (TC 2.A.60) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NYB5-1	1	yes
Q9NYB5-2	2
Q9NYB5-3	3
Q9NYB5-4	4

RefSeq proteins (4): NP_001139416, NP_001139417, NP_001139418, NP_059131* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002350	Kazal_dom	Domain
IPR004156	OATP	Family
IPR020846	MFS_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF03137, PF07648

Catalyzed reactions (Rhea), 3 shown:

• 3,3’,5’-triiodo-L-thyronine(out) = 3,3’,5’-triiodo-L-thyronine(in) (RHEA:71815)
• L-thyroxine(out) = L-thyroxine(in) (RHEA:71819)
• L-thyroxine sulfate(out) = L-thyroxine sulfate(in) (RHEA:73311)

UniProt features (41 total): topological domain 13, transmembrane region 12, glycosylation site 4, disulfide bond 3, splice variant 3, sequence conflict 3, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9DXP	ELECTRON MICROSCOPY	2.3
9DXO	ELECTRON MICROSCOPY	2.6
9MR5	ELECTRON MICROSCOPY	3.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYB5-F1	78.23	0.43

Functional residue map

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

Disulfide bonds (3): 476–506, 482–502, 491–523

Glycosylation sites (4): 146, 510, 520, 533

Mutagenesis-validated functional residues (1):

Position	Phenotype
130	gain of ph-sensitivity of e1s transport.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-879518	Organic anion transport by SLCO transporters
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 101 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_SODIUM_INDEPENDENT_ORGANIC_ANION_TRANSPORT, WWTAAGGC_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_HORMONE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, CEBP_Q2, TGCTGAY_UNKNOWN, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BILE_ACID_AND_BILE_SALT_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT

GO Biological Process (8): monoatomic ion transport (GO:0006811), bile acid and bile salt transport (GO:0015721), sodium-independent organic anion transport (GO:0043252), transmembrane transport (GO:0055085), thyroid hormone transport (GO:0070327), transport across blood-brain barrier (GO:0150104), positive regulation of thyroid hormone generation (GO:2000611), lipid transport (GO:0006869)

GO Molecular Function (6): obsolete organic anion transmembrane transporter activity (GO:0008514), bile acid transmembrane transporter activity (GO:0015125), obsolete sodium-independent organic anion transmembrane transporter activity (GO:0015347), thyroid hormone transmembrane transporter activity (GO:0015349), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (3): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SLC-mediated transport of organic anions	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
transmembrane transport	2
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
cellular process	1
hormone transport	1
vascular transport	1
thyroid hormone generation	1
positive regulation of hormone metabolic process	1
regulation of thyroid hormone generation	1
lipid localization	1
bile acid and bile salt transport	1
carboxylic acid transmembrane transporter activity	1
lipid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
thyroid hormone transport	1
binding	1
transporter activity	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLCO1C1	SLC16A2	P36021	980
SLCO1C1	SLC16A10	Q8TF71	825
SLCO1C1	DIO2	Q92813	794
SLCO1C1	SLC7A8	Q9UHI5	727
SLCO1C1	SLC10A1	Q14973	722
SLCO1C1	DIO3	P55073	704
SLCO1C1	TRH	P20396	649
SLCO1C1	ABCB11	O95342	593
SLCO1C1	SLC7A5	Q01650	587
SLCO1C1	SLC22A8	Q8TCC7	585
SLCO1C1	SLC22A7	Q9Y694	552
SLCO1C1	PDE3A	Q14432	545
SLCO1C1	TTR	P02766	507
SLCO1C1	ABCC3	O15438	490
SLCO1C1	SERPINA7	P05543	488
SLCO1C1	ABCC4	O15439	488

IntAct

270 interactions, top by confidence:

A	B	Type	Score
SCRIB	SLCO1C1	psi-mi:“MI:0915”(physical association)	0.710
SLCO1C1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.710
SCRIB	SLCO1C1	psi-mi:“MI:0407”(direct interaction)	0.710
SLCO1C1	DLG1	psi-mi:“MI:0915”(physical association)	0.610
SLCO1C1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.610
SLCO1C1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.610
SLCO1C1	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
SLCO1C1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.610
SLCO1C1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.610
MAGI2	SLCO1C1	psi-mi:“MI:0407”(direct interaction)	0.610
DLG4	SLCO1C1	psi-mi:“MI:0407”(direct interaction)	0.610
DLG4	SLCO1C1	psi-mi:“MI:0915”(physical association)	0.610
MAGI2	SLCO1C1	psi-mi:“MI:0915”(physical association)	0.610
PDZRN4	SLCO1C1	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	SLCO1C1	psi-mi:“MI:0915”(physical association)	0.610
MAST2	SLCO1C1	psi-mi:“MI:0915”(physical association)	0.610
SLCO1C1	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (19): SLCO1C1 (Affinity Capture-MS), SLCO1C1 (Cross-Linking-MS (XL-MS)), SLCO1C1 (Affinity Capture-MS), ABCA3 (Affinity Capture-MS), AMFR (Affinity Capture-MS), CGRRF1 (Affinity Capture-MS), CPVL (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), DPY19L1 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), ITGB1 (Affinity Capture-MS), ITM2C (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), SEP15 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7R6, A4IF94, A4IHK6, A5D7V7, B2RYH9, F5H094, G3V0H7, O35913, O75387, O80905, O88397, P46720, P46721, P70187, P70502, P81721, Q08C75, Q0VCM6, Q28E13, Q28FF3, Q4LE88, Q4R877, Q5BK75, Q5F4B8, Q5RBM3, Q5RF58, Q5SR56, Q7Z3Q1, Q8BSM7, Q8C0T7, Q8CA03, Q8CGA3, Q8CIA9, Q8N370, Q91498, Q91514, Q91YY5, Q96MC6, Q99J94, Q99PL8

Diamond homologs: F5H094, G3V0H7, O35913, O88397, O94956, P46720, P46721, P70502, Q00910, Q5RFF0, Q6ZQN7, Q71MB6, Q8BGD4, Q8BXB6, Q8HYW2, Q8R3L5, Q91YY5, Q92959, Q96BD0, Q99J94, Q99N01, Q99N02, Q9EP96, Q9EPT5, Q9EPZ7, Q9ERB5, Q9GMU6, Q9H2Y9, Q9JHI3, Q9JJL3, Q9NPD5, Q9NYB5, Q9QXZ6, Q9QYE2, Q9QZX8, Q9UIG8, Q9Y6L6, Q8K078, Q86UG4, Q9VVH9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	40.8×	6e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	38.8×	6e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	38.8×	6e-06
Assembly and cell surface presentation of NMDA receptors	10	36.2×	1e-11
Dopamine Neurotransmitter Release Cycle	5	35.5×	8e-06
Long-term potentiation	5	34.0×	9e-06
Neurexins and neuroligins	11	30.9×	9e-12
Protein-protein interactions at synapses	7	26.6×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	62.7×	4e-15
receptor clustering	8	49.0×	8e-10
protein localization to synapse	6	45.1×	4e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	34.0×	2e-07
bicellular tight junction assembly	5	16.2×	6e-04
Rho protein signal transduction	5	12.2×	2e-03
cell-cell adhesion	10	9.9×	6e-06
regulation of small GTPase mediated signal transduction	6	8.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3113 predictions. Top by Δscore:

Variant	Effect	Δscore
12:20696903:G:GG	donor_gain	1.0000
12:20696909:C:G	donor_gain	1.0000
12:20699719:G:GT	donor_gain	1.0000
12:20706082:G:GG	donor_gain	1.0000
12:20715119:T:TA	acceptor_gain	1.0000
12:20715136:A:AG	acceptor_gain	1.0000
12:20715137:A:G	acceptor_gain	1.0000
12:20715138:G:GG	acceptor_gain	1.0000
12:20717124:T:A	acceptor_gain	1.0000
12:20717130:AG:A	acceptor_gain	1.0000
12:20717131:GG:G	acceptor_gain	1.0000
12:20717131:GGGT:G	acceptor_gain	1.0000
12:20735943:T:G	donor_gain	1.0000
12:20737268:ATATT:A	donor_gain	1.0000
12:20737273:G:GG	donor_gain	1.0000
12:20750674:GCA:G	acceptor_gain	1.0000
12:20696902:A:AG	donor_gain	0.9900
12:20706079:GCA:G	donor_gain	0.9900
12:20713708:A:AG	donor_gain	0.9900
12:20713716:A:T	donor_gain	0.9900
12:20715137:A:AT	acceptor_loss	0.9900
12:20715184:T:A	acceptor_gain	0.9900
12:20715282:ATTG:A	donor_loss	0.9900
12:20715284:TGGT:T	donor_loss	0.9900
12:20715286:GT:G	donor_loss	0.9900
12:20715287:T:A	donor_loss	0.9900
12:20717228:TAGGT:T	donor_loss	0.9900
12:20717230:GGTAA:G	donor_loss	0.9900
12:20717231:GTAAG:G	donor_loss	0.9900
12:20717232:TAA:T	donor_loss	0.9900

AlphaMissense

4605 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:20701381:A:C	S65R	0.998
12:20701383:C:A	S65R	0.998
12:20701383:C:G	S65R	0.998
12:20721838:G:C	W270C	0.998
12:20721838:G:T	W270C	0.998
12:20721848:T:A	W274R	0.998
12:20721848:T:C	W274R	0.998
12:20737185:G:C	W487C	0.998
12:20737185:G:T	W487C	0.998
12:20701447:A:C	S87R	0.997
12:20701449:T:A	S87R	0.997
12:20701449:T:G	S87R	0.997
12:20705975:A:C	S100R	0.997
12:20705977:C:A	S100R	0.997
12:20705977:C:G	S100R	0.997
12:20721851:T:A	W275R	0.997
12:20721851:T:C	W275R	0.997
12:20737240:T:A	C506S	0.997
12:20737241:G:C	C506S	0.997
12:20701408:T:C	F74L	0.996
12:20701410:T:A	F74L	0.996
12:20701410:T:G	F74L	0.996
12:20750724:C:G	C616W	0.996
12:20715186:G:C	G193R	0.995
12:20715187:G:A	G193D	0.995
12:20715201:G:A	G198R	0.995
12:20715201:G:C	G198R	0.995
12:20715208:G:A	G200E	0.995
12:20717171:G:A	G239D	0.995
12:20721836:T:A	W270R	0.995

dbSNP variants (sampled 300 via entrez): RS1000011778 (12:20705057 T>C), RS1000112154 (12:20751636 C>T), RS1000159764 (12:20728617 G>T), RS1000187242 (12:20722125 C>G,T), RS1000270200 (12:20729585 G>C,T), RS1000274652 (12:20751430 A>C), RS1000305516 (12:20748247 G>A,T), RS1000388000 (12:20722313 G>C), RS1000471105 (12:20713483 T>C), RS1000478961 (12:20718187 A>C,G), RS1000499602 (12:20727410 G>A), RS1000526568 (12:20704569 C>A,T), RS1000572248 (12:20736094 T>C), RS1000701379 (12:20728281 C>T), RS1000705378 (12:20723731 T>A)

Disease associations

OMIM: gene MIM:613389 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000175_11	Height	2.000000e-06
GCST000817_181	Height	8.000000e-18
GCST001510_8	Response to TNF-alpha inhibitors in rheumatoid arthritis	4.000000e-06
GCST002647_46	Height	2.000000e-21
GCST006190_49	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-18
GCST006190_72	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-17
GCST006192_59	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-14
GCST006192_70	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-14
GCST006193_32	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-17
GCST006193_71	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-16
GCST006195_14	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-14
GCST006195_63	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	7.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073697 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3794271	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Arthritis;Psoriatic;Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3794271	SLCO1C1	3	1.75	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLCO family of organic anion transporting polypeptides

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	2
Benzo(a)pyrene	increases mutagenesis, decreases methylation	2
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Valproic Acid	increases methylation	1
Zinc	increases expression	1
Zinc Sulfate	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075308	Functional	TP_TRANSPORTER: uptake in Xenopus laevis oocytes	Localization of organic anion transporting polypeptides in the rat and human ciliary body epithelium. — Exp Eye Res

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder