SLC25A3

solute carrier family 25 member 3, the group of Solute carrier family 25|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 12:98593591-98606379

Previous symbols: [ "PHC" ]

Links

ENSG00000075415 ∙ NCBI:5250 ∙ OMIM:600370 ∙ HGNC:10989 ∙ Uniprot:Q00325 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiomyopathy-hypotonia-lactic acidosis syndrome (Supportive), mode of inheritance: AR
• cardiomyopathy-hypotonia-lactic acidosis syndrome (Limited), mode of inheritance: AR
• cardiomyopathy-hypotonia-lactic acidosis syndrome (Strong), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial phosphate carrier deficiency	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; Cardiovascular; Musculoskeletal; Neurologic	17273968

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A3 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A3 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			4	35	1	40
missense			51	2		53
nonsense						0
start loss						0
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)		3			1	4
splice region			4	3	1	8
non coding		1	13	42	16	72
Total	2	4	68	79	18

Highest pathogenic variant AF is 0.0000132

Variants in SLC25A3

This is a list of pathogenic ClinVar variants found in the SLC25A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-98593625-G-C		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jan 13, 2018)
12-98593653-G-A		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Benign/Likely benign (Jul 15, 2018)
12-98593667-G-A		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Benign (Jan 12, 2018)
12-98593671-C-T		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Likely benign (Jan 13, 2018)
12-98593676-G-A		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jan 13, 2018)
12-98593684-G-T		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jan 12, 2018)
12-98593707-C-G		not specified	Benign (Jan 08, 2013)
12-98593707-C-T		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jan 12, 2018)
12-98593757-C-A		not specified	Likely benign (Dec 30, 2016)
12-98593760-C-T		not specified	Likely benign (Oct 13, 2017)
12-98593954-C-T		not specified	Likely benign (Oct 24, 2017)
12-98593968-C-T		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jan 13, 2018)
12-98593982-T-C		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jan 12, 2018)
12-98593984-C-G			Uncertain significance (Jun 30, 2022)
12-98593987-G-A			Likely benign (Sep 19, 2023)
12-98593989-C-T			Uncertain significance (Nov 08, 2022)
12-98593996-G-A			Likely benign (Dec 11, 2023)
12-98593999-C-T			Likely benign (May 03, 2022)
12-98594000-C-G			Uncertain significance (May 13, 2022)
12-98594000-C-T			Likely benign (Oct 05, 2023)
12-98594014-C-A			Uncertain significance (Apr 06, 2022)
12-98594014-C-T			Likely benign (Mar 08, 2023)
12-98594016-C-T			Uncertain significance (Aug 02, 2016)
12-98594027-C-G		Cardiomyopathy-hypotonia-lactic acidosis syndrome	Uncertain significance (Jun 02, 2023)
12-98594028-C-T			Uncertain significance (Nov 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A3	protein_coding	protein_coding	ENST00000228318	7	8578

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0748	0.923	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	155	205	0.756	0.0000106	2340
Missense in Polyphen		44	75.514	0.58267		908
Synonymous	0.369	71	75.1	0.946	0.00000375	739
Loss of Function	2.68	5	16.9	0.296	8.82e-7	201

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transport of phosphate groups from the cytosol to the mitochondrial matrix. Phosphate is cotransported with H(+). May play a role regulation of the mitochondrial permeability transition pore (mPTP).
• Disease: DISEASE: Mitochondrial phosphate carrier deficiency (MPCD) [MIM:610773]: Fatal disorder of oxidative phosphorylation. Patients have lactic acidosis, hypertrophic cardiomyopathy and muscular hypotonia and die within the first year of life. {ECO:0000269|PubMed:17273968}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: C-MYB transcription factor network (Consensus)

Recessive Scores

• pRec: 0.227

Intolerance Scores

• loftool: 0.359
• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.302
• hipred: N
• hipred_score: 0.427
• ghis: 0.612

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.823

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc25a3
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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); embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Gene ontology

• Biological process: phosphate ion transmembrane transport;proton transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of plasma membrane;membrane;integral component of mitochondrial inner membrane;myelin sheath;extracellular exosome
• Molecular function: inorganic phosphate transmembrane transporter activity;phosphate:proton symporter activity;protein-containing complex binding