SLC6A9

solute carrier family 6 member 9, the group of Solute carrier family 6

Basic information

Region (hg38): 1:43991500-44031467

Links

ENSG00000196517 ∙ NCBI:6536 ∙ OMIM:601019 ∙ HGNC:11056 ∙ Uniprot:P48067 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atypical glycine encephalopathy (Strong), mode of inheritance: AR
• infantile glycine encephalopathy (Supportive), mode of inheritance: AR
• atypical glycine encephalopathy (Supportive), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycine encephalopathy with normal serum glycine	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	27481395; 27773429

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A9 gene.

• Atypical glycine encephalopathy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A9 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			2	76	7	85
missense		2	92	7	1	102
nonsense	1					1
start loss			1			1
frameshift	1	1	3			5
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			3	9	2	14
non coding		1	2	34	28	65
Total	2	5	100	117	36

Variants in SLC6A9

This is a list of pathogenic ClinVar variants found in the SLC6A9 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-43991892-C-G		not specified	Uncertain significance (Dec 02, 2022)
1-43991921-C-G		not specified	Uncertain significance (May 04, 2022)
1-43991966-G-C		not specified	Uncertain significance (Sep 01, 2021)
1-43992240-A-G		not specified	Uncertain significance (Mar 16, 2022)
1-43992246-G-C		not specified	Uncertain significance (Oct 13, 2023)
1-43992330-G-A		not specified	Uncertain significance (Feb 22, 2023)
1-43992338-C-T		not specified	Uncertain significance (Aug 16, 2021)
1-43992367-C-G		not specified	Likely benign (Mar 27, 2023)
1-43992375-T-C		not specified	Uncertain significance (Jun 24, 2022)
1-43992376-C-T			Likely benign (Feb 01, 2023)
1-43992525-A-G		not specified	Uncertain significance (Apr 06, 2022)
1-43992614-T-C		not specified	Uncertain significance (Jul 14, 2021)
1-43992619-G-T		not specified	Uncertain significance (Mar 31, 2023)
1-43993907-G-T		not specified	Uncertain significance (Feb 03, 2022)
1-43993930-G-A		not specified	Uncertain significance (Dec 20, 2023)
1-43993948-G-T		not specified	Uncertain significance (Nov 07, 2023)
1-43995611-A-G		not specified	Uncertain significance (Dec 01, 2022)
1-43995979-C-T		not specified	Likely benign (Feb 27, 2023)
1-43996054-G-A		not specified	Likely benign (Sep 29, 2023)
1-43996116-G-T		not specified	Uncertain significance (Mar 01, 2024)
1-43996126-C-T		not specified	Uncertain significance (Jul 14, 2023)
1-43996149-G-A		not specified	Uncertain significance (Nov 07, 2022)
1-43997498-G-A			Benign (May 16, 2021)
1-43997532-C-T			Benign (May 16, 2021)
1-43997553-G-A		Atypical glycine encephalopathy	Uncertain significance (Jun 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A9	protein_coding	protein_coding	ENST00000360584	14	39968

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000217	1.00	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	331	449	0.737	0.0000282	4597
Missense in Polyphen		136	227.39	0.59808		2405
Synonymous	0.122	188	190	0.989	0.0000132	1463
Loss of Function	3.24	14	34.6	0.405	0.00000167	352

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000489	0.000488
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000108	0.000105
Middle Eastern	0.000110	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May play a role in regulation of glycine levels in NMDA receptor-mediated neurotransmission.
• Pathway: Nuclear Receptors Meta-Pathway;NRF2 pathway;Amine compound SLC transporters;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Na+/Cl- dependent neurotransmitter transporters (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• loftool: 0.567
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.67

Haploinsufficiency Scores

• pHI: 0.337
• hipred: Y
• hipred_score: 0.639
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.860

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc6a9
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype

Zebrafish Information Network

• Gene name: slc6a9
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: movement quality

Gene ontology

• Biological process: amino acid transmembrane transport;regulation of synaptic transmission, glycinergic;glycine secretion, neurotransmission
• Cellular component: plasma membrane;integral component of plasma membrane;postsynaptic density;membrane;integral component of synaptic vesicle membrane;hippocampal mossy fiber to CA3 synapse;parallel fiber to Purkinje cell synapse;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: glycine transmembrane transporter activity;glycine:sodium symporter activity