SLC22A1

solute carrier family 22 member 1, the group of Solute carrier family 22

Basic information

Region (hg38): 6:160121814-160158718

Links

ENSG00000175003 ∙ NCBI:6580 ∙ OMIM:602607 ∙ HGNC:10963 ∙ Uniprot:O15245 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC22A1 gene.

• Inborn genetic diseases (25 variants)
• not provided (7 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC22A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense			25		3	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	25	1	7

Variants in SLC22A1

This is a list of pathogenic ClinVar variants found in the SLC22A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-160121967-T-C		not specified	Uncertain significance (Oct 25, 2022)
6-160122009-T-C		not specified	Uncertain significance (Dec 16, 2021)
6-160122053-G-A		not specified	Uncertain significance (Jun 23, 2023)
6-160122060-T-G		not specified	Uncertain significance (Jun 12, 2023)
6-160122098-G-T		not specified	Uncertain significance (Nov 23, 2021)
6-160122150-A-G		not specified	Uncertain significance (Jul 27, 2022)
6-160122171-C-T		not specified	Uncertain significance (Feb 05, 2024)
6-160122173-G-A		not specified	Uncertain significance (Aug 08, 2022)
6-160122276-G-A		not specified	Uncertain significance (May 10, 2023)
6-160122326-G-A		not specified	Uncertain significance (Aug 16, 2022)
6-160130145-T-G		not specified	Uncertain significance (Aug 12, 2021)
6-160130185-G-T			Benign (Apr 10, 2018)
6-160130186-G-A		not specified	Uncertain significance (Feb 13, 2024)
6-160130195-A-G		not specified	Uncertain significance (Aug 12, 2022)
6-160130197-T-C		not specified	Uncertain significance (Dec 12, 2023)
6-160132239-C-T		Aganglionic megacolon	Uncertain significance (May 16, 2019)
6-160132240-G-T		not specified	Uncertain significance (Jul 20, 2022)
6-160132255-T-C		not specified	Uncertain significance (Jan 07, 2022)
6-160132274-C-T			Benign (Jun 13, 2018)
6-160132315-T-G		not specified	Uncertain significance (May 09, 2023)
6-160132354-G-C		not specified	Uncertain significance (Feb 28, 2024)
6-160133990-C-T		not specified	Uncertain significance (Jan 26, 2022)
6-160136229-G-A			Likely benign (Dec 31, 2019)
6-160136288-A-G		not specified	Uncertain significance (May 03, 2023)
6-160136571-G-A		not specified	Uncertain significance (Dec 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC22A1	protein_coding	protein_coding	ENST00000366963	11	36930

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.46e-22	0.0000934	125549	0	199	125748	0.000792

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0948	339	334	1.01	0.0000199	3554
Missense in Polyphen		120	117.76	1.019		1331
Synonymous	-0.646	165	155	1.07	0.0000108	1165
Loss of Function	-1.09	30	24.2	1.24	0.00000112	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00252	0.00245
Ashkenazi Jewish	0.00	0.00
East Asian	0.00125	0.00114
Finnish	0.000150	0.000139
European (Non-Finnish)	0.000897	0.000827
Middle Eastern	0.00125	0.00114
South Asian	0.000502	0.000490
Other	0.00101	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase. {ECO:0000269|PubMed:11388889, ECO:0000269|PubMed:11408531, ECO:0000269|PubMed:15389554, ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093, ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9655880}.
• Pathway: Choline metabolism in cancer - Homo sapiens (human);Bile secretion - Homo sapiens (human);Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics;Tramadol Pharmacokinetics;Metformin Pathway, Pharmacokinetics;Tramadol Metabolism Pathway;Lamivudine Metabolism Pathway;Amine compound SLC transporters;Abacavir transmembrane transport;Abacavir transport and metabolism;Metabolism;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Neuronal System;Organic cation transport;Organic cation/anion/zwitterion transport;Prostaglandin formation from arachidonate;Tryptophan metabolism;Na+/Cl- dependent neurotransmitter transporters;Neurotransmitter release cycle;Neurotransmitter clearance;Transmission across Chemical Synapses;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.205

Intolerance Scores

• loftool: 0.920
• rvis_EVS: 1.78
• rvis_percentile_EVS: 96.85

Haploinsufficiency Scores

• pHI: 0.0641
• hipred: N
• hipred_score: 0.170

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.715

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc22a1
• Phenotype: liver/biliary system phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: neurotransmitter transport;drug transmembrane transport;establishment or maintenance of transmembrane electrochemical gradient;organic cation transport;quaternary ammonium group transport;epinephrine transport;protein homooligomerization;norepinephrine uptake;ammonium transmembrane transport;dopamine uptake;acetate ester transport
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;basolateral plasma membrane
• Molecular function: acetylcholine transmembrane transporter activity;dopamine:sodium symporter activity;norepinephrine:sodium symporter activity;protein binding;secondary active organic cation transmembrane transporter activity;organic cation transmembrane transporter activity;quaternary ammonium group transmembrane transporter activity;protein homodimerization activity