SLC6A7

protein-coding

solute carrier family 6 member 7, the group of Solute carrier family 6

Gene summary

This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014228.5

Inheritance

—

ClinVar variants

U:112B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr5:150,190,062-150,222,788

External References & Databases

Ensembl (ENSG00000011083)

Transcript & Mutation Effects

hg38 • Region Span ~32.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC6A7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014228.5. 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		3 clinvar	4
missense			111 clinvar			111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	112	0	3	115

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014228.5	RefSeq	NP_055043.2	14	MANE Select
ENST00000230671.7	Ensembl	ENSP00000230671.2	14	MANE Select
ENST00000524041.1	Ensembl	ENSP00000428200.1	16	Standard
ENST00000524041.2	Ensembl	ENSP00000428200.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nuclear Receptors Meta-Pathway
NRF2 pathway
Amine compound SLC transporters
Metabolism of polyamines
Metabolism of amino acids and derivatives

Biological Process

neurotransmitter transport
proline transport
proline transmembrane transport

Molecular Function

proline:sodium symporter activity
neurotransmitter:sodium symporter activity
L-proline transmembrane transporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000230671
Coding exons: 14
Length: 32832
Individuals with no LoFs: 125682
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125748
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.520	360	389	0.926	0.0000233	4106
Missense (PolyPhen)		159	190.47	0.83479		2080
Synonymous	0.249	164	168	0.976	0.0000109	1309
Loss of Function	2.08	20	32.9	0.608	0.00000162	346

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00050	0.00049	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals.;

Recessive Scores

pRec: 0.513

Intolerance Scores

LoFtool: 0.473
RVIS EVS: -1.29
RVIS percentile EVS: 5.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.240

Gene Damage Prediction

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