SLC25A19

solute carrier family 25 member 19, the group of Solute carrier family 25

Basic information

Region (hg38): 17:75272981-75289510

Previous symbols: [ "MCPHA" ]

Links

ENSG00000125454

∙ NCBI:60386 ∙ OMIM:606521 ∙ HGNC:14409 ∙ Uniprot:Q9HC21 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Amish lethal microcephaly (Strong), mode of inheritance: AR
Amish lethal microcephaly (Strong), mode of inheritance: AR
progressive demyelinating neuropathy with bilateral striatal necrosis (Strong), mode of inheritance: AR
Amish lethal microcephaly (Supportive), mode of inheritance: AR
progressive demyelinating neuropathy with bilateral striatal necrosis (Supportive), mode of inheritance: AR
Amish lethal microcephaly (Strong), mode of inheritance: AR
progressive demyelinating neuropathy with bilateral striatal necrosis (Strong), mode of inheritance: AR
Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thiamine metabolism dysfunction syndrome 4; Microcephaly, Amish type	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	12185364; 19798730; 20583149
High fat diet has been reported as being beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A19 gene.

not_provided (111 variants)
Inborn_genetic_diseases (37 variants)
Amish_lethal_microcephaly (22 variants)
not_specified (21 variants)
Progressive_demyelinating_neuropathy_with_bilateral_striatal_necrosis (16 variants)
SLC25A19-related_disorder (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A19 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001126121.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				36 clinvar		36
missense	10 clinvar	3 clinvar	63 clinvar	9 clinvar		85
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	11	3	64	45	0

Highest pathogenic variant AF is 0.000025403671

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A19	protein_coding	protein_coding	ENST00000402418	6	16519

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.649	0.350	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.587	171	194	0.881	0.0000121	2082
Missense in Polyphen		31	54.564	0.56814		564
Synonymous	0.539	74	80.1	0.923	0.00000547	654
Loss of Function	2.68	2	12.0	0.166	5.19e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Mitochondrial transporter mediating uptake of thiamine pyrophosphate (ThPP) into mitochondria. {ECO:0000269|PubMed:18280798}.;
Disease: DISEASE: Thiamine metabolism dysfunction syndrome 4, bilateral striatal degeneration and progressive polyneuropathy type (THMD4) [MIM:613710]: A disease characterized by recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. {ECO:0000269|PubMed:19798730}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Vitamin B1 (thiamin) metabolism;Purine metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Pyrimidine metabolism;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

pRec: 0.178

Intolerance Scores

loftool: 0.128
rvis_EVS: -0.43
rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

pHI: 0.137
hipred: Y
hipred_score: 0.551
ghis: 0.590

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: N
gene_indispensability_score: 0.460

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc25a19
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); renal/urinary system phenotype; embryo phenotype; 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); hematopoietic system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: deoxynucleotide transport;thiamine pyrophosphate transmembrane transport;thiamine-containing compound metabolic process;thiamine transmembrane transport
Cellular component: nucleus;mitochondrial inner membrane;integral component of mitochondrial inner membrane
Molecular function: thiamine transmembrane transporter activity;deoxynucleotide transmembrane transporter activity;thiamine pyrophosphate transmembrane transporter activity