SLC66A1

protein-coding

solute carrier family 66 member 1, the group of Solute carrier family 66

Gene summary

Enables L-arginine transmembrane transporter activity; L-histidine transmembrane transporter activity; and L-lysine transmembrane transporter activity. Involved in L-amino acid transport and intracellular amino acid homeostasis. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

PQLC2

MANE transcript

NM_001040125.2

Inheritance

ClinVar variants

P:1U:64B:3

Top phenotype

retinitis pigmentosa

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr1:19,312,326-19,329,300

External References & Databases

Ensembl (ENSG00000040487)

Transcript & Mutation Effects

hg38 • Region Span ~17.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019200

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC66A1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 2

Nephropathic cystinosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040125.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			57 clinvar	3 clinvar		60
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)	1 clinvar		5 clinvar			6
Total	1	0	64	3	0	68

Highest pathogenic variant AF is 0.000020447565

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040125.2	RefSeq	NP_001035214.1	7	MANE Select
ENST00000375153.8	Ensembl	ENSP00000364295.3	7	MANE Select
NM_001040126.2	RefSeq	NP_001035215.1	6	Standard
NM_001287531.2	RefSeq	NP_001274460.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of small molecules
Miscellaneous transport and binding events

Biological Process

arginine transport
lysine transport
transmembrane transport
amino acid homeostasis
L-lysine transmembrane transport

Molecular Function

basic amino acid transmembrane transporter activity
arginine transmembrane transporter activity
L-lysine transmembrane transporter activity

Cellular Component

lysosomal membrane
integral component of organelle membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375153
Coding exons: 7
Length: 16975
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.976	149	187	0.799	0.0000122	1848
Missense (PolyPhen)		29	50.553	0.57365		523
Synonymous	0.669	83	91.1	0.911	0.00000646	632
Loss of Function	1.56	9	15.6	0.575	9.61e-7	143

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Amino acid transporter that specifically mediates the pH-dependent export of the cationic amino acids arginine, histidine and lysine from lysosomes. {ECO:0000269|PubMed:22822152, ECO:0000269|PubMed:23169667}.;

Intolerance Scores

LoFtool: 0.295
RVIS EVS: 0.17
RVIS percentile EVS: 65.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.434

Gene Damage Prediction

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