SLC25A21

protein-coding

solute carrier family 25 member 21, the group of Solute carrier family 25|MicroRNA protein coding host genes

Gene summary

SLC25A21 is a homolog of the S. cerevisiae ODC proteins, mitochondrial carriers that transport C5-C7 oxodicarboxylates across inner mitochondrial membranes. One of the species transported by ODC is 2-oxoadipate, a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine in mammals. Within mitochondria, 2-oxoadipate is converted into acetyl-CoA.[supplied by OMIM, Apr 2004]

MANE transcript

NM_030631.4

Inheritance

ClinVar variants

P:2U:84B:34

Top phenotype

Mitochondrial DNA depletion syndrome 18

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr14:36,677,921-37,172,606

External References & Databases

Ensembl (ENSG00000183032)

Transcript & Mutation Effects

hg38 • Region Span ~494.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial DNA depletion syndrome 18LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032932

Submitter: Ambry Genetics

mitochondrial DNA depletion syndrome 18LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032932

Submitter: Labcorp Genetics (formerly Invitae)

mitochondrial DNA depletion syndrome 18MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032932

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Mitochondrial DNA depletion syndrome 18AR

Manifestation: Biochemical; Neurologic

Intervention: General

Rationale: 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

Refs: 29517768

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC25A21 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 120

not specifiedTotal: 48

Mitochondrial DNA depletion syndrome 18Total: 3

SLC25A21-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030631.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	21 clinvar		22
missense	1 clinvar		73 clinvar	8 clinvar	4 clinvar	86
nonsense		1 clinvar	3 clinvar	1 clinvar		5
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	1	84	30	4	120

Highest pathogenic variant AF is 0.00003717707

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030631.4	RefSeq	NP_085134.1	10	MANE Select
ENST00000331299.6	Ensembl	ENSP00000329452.5	10	MANE Select
NM_001171170.2	RefSeq	NP_001164641.1	11	Standard
ENST00000555449.5	Ensembl	ENSP00000451873.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine catabolism
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism
Metabolism of amino acids and derivatives
Metabolism
Lysine metabolism

Biological Process

lysine catabolic process
alpha-ketoglutarate transport
transmembrane transport

Molecular Function

alpha-ketoglutarate transmembrane transporter activity

Cellular Component

mitochondrial inner membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331299
Coding exons: 10
Length: 494436
Individuals with no LoFs: 125602
Homozygous LoFs: 0
Heterozygous LoFs: 145
Defined: 125747
p: 0.000577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0246	149	150	0.994	0.00000681	1905
Missense (PolyPhen)		73	67.007	1.0894		903
Synonymous	-0.375	57	53.5	1.07	0.00000254	569
Loss of Function	0.120	17	17.5	0.969	9.04e-7	217

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.0018	0.0018	notable
East Asian	0.0025	0.0024	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00084	0.00082	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transports C5-C7 oxodicarboxylates across the inner membranes of mitochondria. Can transport 2-oxoadipate, 2- oxoglutarate, adipate, glutarate, and to a lesser extent, pimelate, 2-oxopimelate, 2-aminoadipate, oxaloacetate, and citrate.;

Recessive Scores

pRec: 0.267

Intolerance Scores

LoFtool: 0.617
RVIS EVS: 0.73
RVIS percentile EVS: 86.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.336

Gene Damage Prediction

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