Citrin deficiency

Summary

Citrin deficiency (MONDO:0016602) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 697
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	citrin deficiency
Mondo ID	MONDO:0016602
Orphanet	247582
ICD-11	348535193
SNOMED CT	429735007
UMLS	C1997910
MedGen	372684
GARD	0020661
Is cancer (heuristic)	no

Also known as: citrin deficiency

Data availability: 697 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › urea cycle disorder › citrullinemia › citrin deficiency

Related subtypes (1): citrullinemia type I

Subtypes (2): neonatal intrahepatic cholestasis due to citrin deficiency, citrullinemia type II

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

377 likely benign, 72 pathogenic, 58 uncertain significance, 27 pathogenic/likely pathogenic, 25 likely pathogenic, 25 conflicting classifications of pathogenicity, 12 benign, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
21510	NM_014251.3(SLC25A13):c.15G>A (p.Lys5=)	LOC129998833	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067978	NM_014251.3(SLC25A13):c.1231-1G>A	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068567	NM_014251.3(SLC25A13):c.420del (p.Glu141fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1069536	NM_014251.3(SLC25A13):c.1311C>A (p.Cys437Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069861	NC_000007.13:g.(?95906498)(95906660_?)del	SLC25A13	Pathogenic	criteria provided, single submitter
1069995	NM_014251.3(SLC25A13):c.66_67insC (p.Lys23fs)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070090	NM_014251.3(SLC25A13):c.475C>T (p.Gln159Ter)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
1070408	NM_014251.3(SLC25A13):c.1751-5_1751-4insGATTTCTCCATTTTTTTTTTTTTTTTTNNNNNNNNNNGTCCCCCCGCCCCCCGAGCCCGAACCCCTTTCCACTGCCAACACCTCACCTCGCCCCCGCCGCCATCTTCCTCCTCCCTTGGCAGCCCCGCCCCCC	SLC25A13	Pathogenic	criteria provided, single submitter
1071593	NM_014251.3(SLC25A13):c.1173dup (p.Arg392Ter)	SLC25A13	Pathogenic	criteria provided, single submitter
1071972	NC_000007.13:g.(?95838140)(95838299_?)del	SLC25A13	Pathogenic	criteria provided, single submitter
1071973	NC_000007.13:g.(?95761045)(95761203_?)dup	SLC25A13	Pathogenic	criteria provided, single submitter
1073569	NM_014251.3(SLC25A13):c.792del (p.Thr265fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1074032	NM_014251.3(SLC25A13):c.276del (p.Phe92fs)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074885	NM_014251.3(SLC25A13):c.1677C>G (p.Tyr559Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075398	NM_014251.3(SLC25A13):c.1063C>G (p.Arg355Gly)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
1075399	NM_014251.3(SLC25A13):c.173_174del (p.Val58fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1076508	NM_014251.3(SLC25A13):c.429_430del (p.Arg144fs)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323603	NM_014251.3(SLC25A13):c.1173T>G (p.Tyr391Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1351050	NM_014251.3(SLC25A13):c.1633_1637dup (p.Leu548fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1359671	NM_014251.3(SLC25A13):c.1603_1609dup (p.Leu537fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1361197	NM_014251.3(SLC25A13):c.1228dup (p.Thr410fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1361947	NM_014251.3(SLC25A13):c.127C>T (p.Arg43Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362972	NM_014251.3(SLC25A13):c.528dup (p.Arg177fs)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1366582	NM_014251.3(SLC25A13):c.132C>G (p.Tyr44Ter)	SLC25A13	Pathogenic	criteria provided, single submitter
1379532	NM_014251.3(SLC25A13):c.1610del (p.Ser536_Leu537insTer)	SLC25A13	Pathogenic	criteria provided, single submitter
1382583	NM_014251.3(SLC25A13):c.1486_1489del (p.Phe496fs)	SLC25A13	Pathogenic	criteria provided, single submitter
1385282	NM_014251.3(SLC25A13):c.1612del (p.Leu537_Val538insTer)	SLC25A13	Pathogenic	criteria provided, single submitter
1386444	NM_014251.3(SLC25A13):c.94G>T (p.Glu32Ter)	SLC25A13	Pathogenic	criteria provided, single submitter
1388183	NM_014251.3(SLC25A13):c.1453-2A>T	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
1401121	NM_014251.3(SLC25A13):c.848+1G>A	SLC25A13	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A13	Orphanet:247585	Citrullinemia type II
SLC25A13	Orphanet:247598	Neonatal intrahepatic cholestasis due to citrin deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC25A13	HGNC:10983	ENSG00000004864	Q9UJS0	Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A13	Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial	Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC25A13	Transporter	yes		EF_hand_dom, MCP, EF-hand-dom_pair

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right lobe of liver	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A13	283	ubiquitous	marker	right lobe of liver, liver, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A13	1,895

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC25A13	Q9UJS0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Malate-aspartate shuttle	1	1268.9×	0.004	SLC25A13
Aspartate and asparagine metabolism	1	1038.2×	0.004	SLC25A13
Protein localization	1	190.3×	0.012	SLC25A13
Mitochondrial protein import	1	167.9×	0.012	SLC25A13
Respiratory electron transport	1	95.2×	0.015	SLC25A13
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	SLC25A13
Metabolism of amino acids and derivatives	1	67.6×	0.017	SLC25A13
Metabolism	1	11.6×	0.086	SLC25A13

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
malate-aspartate shuttle	1	1872.4×	0.002	SLC25A13
aspartate transmembrane transport	1	1404.3×	0.002	SLC25A13
mitochondrial transport	1	1203.7×	0.002	SLC25A13
ATP biosynthetic process	1	991.3×	0.002	SLC25A13
L-glutamate transmembrane transport	1	802.5×	0.002	SLC25A13
cellular respiration	1	432.1×	0.003	SLC25A13
gluconeogenesis	1	324.1×	0.003	SLC25A13
response to calcium ion	1	318.0×	0.003	SLC25A13

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC25A13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC25A13	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	SLC25A13
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC25A13	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06895746	Not specified	ACTIVE_NOT_RECRUITING	Multi-omics Study in Citrin Deficiency
NCT07055269	Not specified	ACTIVE_NOT_RECRUITING	Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects