SLC25A22

solute carrier family 25 member 22, the group of Solute carrier family 25

Basic information

Region (hg38): 11:790474-798281

Links

ENSG00000177542 ∙ NCBI:79751 ∙ OMIM:609302 ∙ HGNC:19954 ∙ Uniprot:Q9H936 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 3 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
• early myoclonic encephalopathy (Supportive), mode of inheritance: AD
• malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 3 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epileptic encephalopathy, early infantile, 3	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	Neurologic	15592994; 19780765; 24596948
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A22 gene.

• Early infantile epileptic encephalopathy with suppression bursts (371 variants)
• not provided (132 variants)
• Early myoclonic encephalopathy (104 variants)
• not specified (79 variants)
• Inborn genetic diseases (71 variants)
• Developmental and epileptic encephalopathy, 3 (19 variants)
• Early Infantile Epileptic Encephalopathy, Autosomal Recessive (8 variants)
• Seizure (1 variants)
• Developmental delay;Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A22 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	92	3	97
missense	1	1	155	1	1	159
nonsense	5	2	1			8
start loss						0
frameshift	3		2			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2				3
splice region			13	19		32
non coding			52	89	28	169
Total	10	5	214	182	32

Highest pathogenic variant AF is 0.00000657

Variants in SLC25A22

This is a list of pathogenic ClinVar variants found in the SLC25A22 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-790484-A-T		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-790485-ATATT-A		Early Infantile Epileptic Encephalopathy, Autosomal Recessive	Uncertain significance (Jun 14, 2016)
11-790614-G-A		Early myoclonic encephalopathy	Uncertain significance (Mar 23, 2018)
11-790623-A-G		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-790638-G-A		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-790762-G-A		Early myoclonic encephalopathy	Benign (Jan 13, 2018)
11-790831-G-C		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-790858-G-T		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-790874-G-A		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-790902-G-T		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-790915-G-A		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-790975-A-G		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-790978-C-T		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-791009-C-T		Early myoclonic encephalopathy	Benign (Jan 12, 2018)
11-791070-A-T		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-791074-T-A		Early myoclonic encephalopathy	Benign (Jan 13, 2018)
11-791105-G-A		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-791135-G-A		Early Infantile Epileptic Encephalopathy, Autosomal Recessive	Uncertain significance (Jun 14, 2016)
11-791137-C-T		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-791155-C-T		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-791162-C-T		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-791169-C-G		Early myoclonic encephalopathy	Uncertain significance (Jan 12, 2018)
11-791203-A-G		Early myoclonic encephalopathy	Benign (Jan 12, 2018)
11-791204-C-T		Early myoclonic encephalopathy	Uncertain significance (Jan 13, 2018)
11-791209-G-GCA		Early Infantile Epileptic Encephalopathy, Autosomal Recessive	Likely benign (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A22	protein_coding	protein_coding	ENST00000320230	9	7842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00661	0.977	125616	0	13	125629	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.913	168	205	0.820	0.0000153	2009
Missense in Polyphen		78	100.05	0.7796		984
Synonymous	-2.20	122	94.7	1.29	0.00000812	683
Loss of Function	2.09	6	14.6	0.410	6.46e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000377	0.0000352
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000693	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the transport of glutamate across the inner mitochondrial membrane. Glutamate is cotransported with H(+). {ECO:0000269|PubMed:11897791}.
• Pathway: Glucose-Alanine Cycle;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;visual signal transduction;Organic anion transporters;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Vitamin B9 (folate) metabolism (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.354
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.2

Haploinsufficiency Scores

• pHI: 0.403
• hipred: Y
• hipred_score: 0.654
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.610

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc25a22

Gene ontology

• Biological process: ion transport;aspartate transmembrane transport;L-glutamate transmembrane transport;malate-aspartate shuttle;L-aspartate transmembrane transport;proton transmembrane transport
• Cellular component: mitochondrial inner membrane;integral component of membrane
• Molecular function: amino acid:proton symporter activity;L-glutamate transmembrane transporter activity;L-aspartate transmembrane transporter activity