SLC36A2

solute carrier family 36 member 2, the group of Solute carrier family 36

Basic information

Region (hg38): 5:151314972-151347590

Links

ENSG00000186335 ∙ NCBI:153201 ∙ OMIM:608331 ∙ HGNC:18762 ∙ Uniprot:Q495M3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperglycinuria (Limited), mode of inheritance: AD
• hyperglycinuria (Limited), mode of inheritance: Semidominant
• iminoglycinuria (Supportive), mode of inheritance: AR
• iminoglycinuria (Limited), mode of inheritance: AR
• iminoglycinuria (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperglycinuria; Iminoglycinuria; Iminoglycinuria, digenic	AD/AR/Digenic	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; Renal	19033659
Variants in other genes (eg, SLC6A18, SLC6A19, SLC6A20) may affect manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC36A2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC36A2 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				22	10	32
missense			38	11	3	52
nonsense						0
start loss						0
frameshift			4			4
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding				5	24	29
Total	0	0	42	39	37

Variants in SLC36A2

This is a list of pathogenic ClinVar variants found in the SLC36A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-151316610-T-C			Benign (May 15, 2021)
5-151316704-T-C			Benign (May 16, 2021)
5-151316740-C-CA			Benign (May 15, 2021)
5-151316740-C-CAA			Benign (May 15, 2021)
5-151316740-C-CAAA			Benign (May 17, 2021)
5-151316762-A-AAG			Benign (May 16, 2021)
5-151316858-C-T		SLC36A2-related disorder	Conflicting classifications of pathogenicity (Jan 15, 2024)
5-151316868-G-C			Likely benign (Apr 01, 2023)
5-151316877-G-A		Hyperglycinuria;Iminoglycinuria	Likely benign (Mar 20, 2023)
5-151316884-G-A		SLC36A2-related disorder	Uncertain significance (Aug 02, 2023)
5-151316884-G-T			Uncertain significance (Nov 17, 2022)
5-151316886-C-T		Hyperglycinuria	Benign (Jan 30, 2024)
5-151316888-G-C		not specified	Uncertain significance (Mar 30, 2024)
5-151316890-T-G			Uncertain significance (Jun 02, 2022)
5-151316913-G-A			Likely benign (Nov 12, 2023)
5-151316917-C-A		not specified	Uncertain significance (Dec 27, 2023)
5-151316934-G-A			Likely benign (May 26, 2023)
5-151316935-G-A		SLC36A2-related disorder	Benign (Jan 25, 2024)
5-151316936-C-T		not specified	Uncertain significance (Feb 05, 2024)
5-151316937-G-A			Benign (Jan 30, 2024)
5-151316955-G-T			Likely benign (Jul 07, 2022)
5-151316958-G-C			Uncertain significance (May 22, 2023)
5-151316979-C-T		Hyperglycinuria	Benign (Jan 30, 2024)
5-151316979-CGTGGTGA-T			Uncertain significance (Sep 01, 2024)
5-151316998-G-C			Likely benign (Mar 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC36A2	protein_coding	protein_coding	ENST00000335244	10	32613

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.15e-10	0.237	125653	0	95	125748	0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0784	270	274	0.987	0.0000162	3140
Missense in Polyphen		87	79.792	1.0903		976
Synonymous	0.466	104	110	0.944	0.00000660	1005
Loss of Function	0.684	16	19.2	0.832	9.95e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00149	0.00149
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000361	0.000360
Middle Eastern	0.000163	0.000163
South Asian	0.000294	0.000294
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in a pH-dependent electrogenic neuronal transport and sequestration of small amino acids. Transports glycine and proline. Inhibited by sarcosine (By similarity). {ECO:0000250, ECO:0000269|PubMed:19033659}.
• Disease: DISEASE: Iminoglycinuria (IG) [MIM:242600]: A disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine. {ECO:0000269|PubMed:19033659}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Mutations in SLC36A2 that retain residual transport activity result in the IG phenotype only when combined with haploinsufficiency of the imino acid transporter SLC6A20 or deficiency of the neutral amino acid transporter SLC6A19. Additional polymorphisms and mutations in SLC6A18 can contribute to iminoglycinuria in some families.
• Pathway: Amino acid transport across the plasma membrane;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Proton-coupled neutral amino acid transporters (Consensus)

Recessive Scores

• pRec: 0.0970

Intolerance Scores

• loftool: 0.912
• rvis_EVS: 0.05
• rvis_percentile_EVS: 57.52

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.162
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0689

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc36a2

Gene ontology

• Biological process: amino acid transmembrane transport;ion transport;amino acid transport;L-alanine transport;glycine transport;proline transmembrane transport;proton transmembrane transport
• Cellular component: cytoplasm;plasma membrane;integral component of membrane;extracellular exosome
• Molecular function: amino acid:proton symporter activity;proton transmembrane transporter activity;amino acid transmembrane transporter activity;L-alanine transmembrane transporter activity;glycine transmembrane transporter activity;L-proline transmembrane transporter activity