SLC31A1

protein-coding

solute carrier family 31 member 1, the group of Solute carrier family 31

Gene summary

The protein encoded by this gene is a high-affinity copper transporter found in the cell membrane. The encoded protein functions as a homotrimer to effect the uptake of dietary copper. [provided by RefSeq, Aug 2011]

Previous symbols:

COPT1

MANE transcript

NM_001859.4

Inheritance

ClinVar variants

P:2U:20B:4

Top phenotype

Neurodegeneration and seizures due to copper transport defect

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr9:113,221,544-113,264,492

External References & Databases

Ensembl (ENSG00000136868)

Transcript & Mutation Effects

hg38 • Region Span ~42.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodegeneration and seizures due to copper transport defectMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957211

Submitter: G2P

neurodegeneration and seizures due to copper transport defectLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0957211

Submitter: Labcorp Genetics (formerly Invitae)

neurodegeneration and seizures due to copper transport defectMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957211

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodegeneration and seizures due to copper transport defectAR

Manifestation: Biochemical; Neurologic

Intervention: Biochemical

Rationale: The condition can have neurologic sequelae, and medical management (eg, with copper histidinate) has been reported in having some benefit related to both clinical and biochemical parameters

Refs: 35913762; 36562171

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC31A1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 20

not providedTotal: 4

Neurodegeneration and seizures due to copper transport defectTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001859.4. 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 clinvar	2
missense	1 clinvar	1 clinvar	19 clinvar	2 clinvar	1 clinvar	24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	1	20	2	2	26

Highest pathogenic variant AF is 0.0000020521745

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001859.4	RefSeq	NP_001850.1	4	MANE Select
ENST00000374212.5	Ensembl	ENSP00000363329.4	4	MANE Select
ENST00000902243.1	Ensembl	ENSP00000572302.1	4	Standard
ENST00000902243.2	Ensembl	ENSP00000572302.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
slc31a1	Danio rerio	Structure: whole organism Quality: unpigmented abnormal

Gene / Model

Organism

Observed Phenotype

slc31a1

Danio rerio

Structure: whole organism

Quality: unpigmented

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mineral absorption - Homo sapiens (human)
Platinum Pathway, Pharmacokinetics/Pharmacodynamics
Copper homeostasis
Transport of bile salts and organic acids, metal ions and amine compounds
SLC-mediated transmembrane transport

Biological Process

copper ion transport
drug transmembrane transport
cellular copper ion homeostasis
cellular response to cisplatin
copper ion import across plasma membrane

Molecular Function

copper ion transmembrane transporter activity
identical protein binding

Cellular Component

late endosome
plasma membrane
integral component of plasma membrane
neuronal cell body
recycling endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374212
Coding exons: 4
Length: 44867
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125737
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	75	106	0.705	0.00000533	1271
Missense (PolyPhen)		18	37.027	0.48613		466
Synonymous	-0.213	37	35.4	1.05	0.00000185	353
Loss of Function	1.60	3	7.84	0.383	4.21e-7	89

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: High-affinity, saturable copper transporter involved in dietary copper uptake. {ECO:0000269|PubMed:11734551}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.277
RVIS EVS: 0.08
RVIS percentile EVS: 59.76

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: N
Indispensability score: 0.243

Gene Damage Prediction

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