SLC25A19

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

Basic information

Region (hg38): 17:75272980-75289510

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 (124 variants)
• Amish lethal microcephaly (35 variants)
• not specified (23 variants)
• Inborn genetic diseases (16 variants)
• Progressive demyelinating neuropathy with bilateral striatal necrosis (10 variants)
• Progressive demyelinating neuropathy with bilateral striatal necrosis;Amish lethal microcephaly (2 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.

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				25	2	27
missense		3	50	3		56
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region			3	4		7
non coding			5	19	24	48
Total	1	3	56	47	26

Highest pathogenic variant AF is 0.0000197

Variants in SLC25A19

This is a list of pathogenic ClinVar variants found in the SLC25A19 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-75273014-A-C		Amish lethal microcephaly	Benign (Jan 12, 2018)
17-75273043-G-A		Amish lethal microcephaly	Uncertain significance (Jan 13, 2018)
17-75273067-G-A		Amish lethal microcephaly	Uncertain significance (Jan 13, 2018)
17-75273150-G-A		Amish lethal microcephaly	Likely benign (Jan 13, 2018)
17-75273159-T-C		Amish lethal microcephaly	Uncertain significance (Jan 13, 2018)
17-75273177-G-C		Amish lethal microcephaly	Benign (Jun 16, 2018)
17-75273251-C-T		Amish lethal microcephaly	Benign/Likely benign (Apr 16, 2019)
17-75273287-C-T		Amish lethal microcephaly	Benign (Mar 06, 2018)
17-75273338-C-G		Amish lethal microcephaly	Uncertain significance (Jan 13, 2018)
17-75273355-C-G		Amish lethal microcephaly	Likely benign (Sep 29, 2019)
17-75273447-G-A		SLC25A19-related disorder	Likely benign (Jan 22, 2024)
17-75273449-A-G		not specified • Amish lethal microcephaly • Progressive demyelinating neuropathy with bilateral striatal necrosis	Benign (Jul 15, 2021)
17-75273455-C-T			Uncertain significance (Aug 23, 2022)
17-75273475-C-A			Uncertain significance (Jun 24, 2022)
17-75273484-G-T		Amish lethal microcephaly	Uncertain significance (Jun 14, 2016)
17-75273496-G-A		not specified	Likely benign (Nov 08, 2022)
17-75273504-C-T		Progressive demyelinating neuropathy with bilateral striatal necrosis	Pathogenic (Jul 08, 2022)
17-75273508-C-T			Likely benign (Dec 20, 2023)
17-75273509-G-A		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
17-75273509-G-C		Inborn genetic diseases	Likely benign (Jun 25, 2021)
17-75273524-C-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
17-75273535-G-A			Likely benign (Jun 28, 2018)
17-75273545-A-T		Progressive demyelinating neuropathy with bilateral striatal necrosis	Pathogenic (Jul 08, 2022)
17-75273572-A-C		Amish lethal microcephaly • SLC25A19-related disorder	Conflicting classifications of pathogenicity (Feb 27, 2024)
17-75273576-C-T			Uncertain significance (Aug 01, 2022)

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