SLC25A13 (solute carrier family 25 member 13)

Gene

• Entrez ID: 10165
• Gene name: Solute carrier family 25 member 13
• Gene symbol: SLC25A13
• Synonyms (NCBI Gene): ARALAR2, CITRIN, CTLN2, NICCD
• Chromosome: 7
• Chromosome location: 7q21.3
• Summary: This gene is a member of the mitochondrial carrier family. The encoded protein contains four EF-hand Ca(2+) binding motifs in the N-terminal domain, and localizes to mitochondria. The protein catalyzes the exchange of aspartate for glutamate and a proton

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs80338715	C>T	Pathogenic	Synonymous variant, non coding transcript variant, genic upstream transcript variant, coding sequence variant, 5 prime UTR variant
rs80338716	G>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant, 5 prime UTR variant
rs80338717	C>T	Pathogenic, likely-pathogenic	Intron variant
rs80338718	C>G	Pathogenic	Splice donor variant
rs80338719	G>A,T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant, stop gained
rs80338720	ATAC>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant, 5 prime UTR variant, initiator codon variant
rs80338721	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs80338722	C>T	Pathogenic	Splice donor variant
rs80338723	C>A,G,T	Pathogenic	Splice donor variant
rs80338724	C>T	Pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs80338725	->CCCGGGCAGCCACCTGTAATCTC	Pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, frameshift variant
rs80338726	->T,TTT	Pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, stop gained
rs80338727	C>A,T	Pathogenic	Missense variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant, stop gained
rs80338729	G>A	Pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, stop gained
rs121908532	C>T	Uncertain-significance, pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs138094550	A>G	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, synonymous variant, coding sequence variant
rs139149160	G>A	Uncertain-significance, likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs141152495	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, non coding transcript variant, intron variant, coding sequence variant
rs143877538	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	3 prime UTR variant, non coding transcript variant, coding sequence variant, missense variant
rs144494809	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs148962110	A>C,G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, missense variant, genic downstream transcript variant
rs150021522	T>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, synonymous variant
rs180844972	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant
rs199735534	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs200237622	T>G	Likely-pathogenic	3 prime UTR variant, coding sequence variant, non coding transcript variant, missense variant
rs201395793	C>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs376416252	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Synonymous variant, non coding transcript variant, coding sequence variant
rs746155190	G>A,C	Pathogenic	Coding sequence variant, intron variant, non coding transcript variant, stop gained, missense variant
rs747257110	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, non coding transcript variant, synonymous variant
rs758827458	G>A,C	Uncertain-significance, pathogenic	Non coding transcript variant, coding sequence variant, missense variant, stop gained
rs761370420	C>A	Pathogenic	Splice donor variant, intron variant
rs763191789	G>A,C	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant, stop gained
rs764401478	CT>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs765358773	T>C	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, synonymous variant
rs768922690	C>A,T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs879255504	T>-	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, frameshift variant
rs962082210	C>T	Pathogenic	Splice acceptor variant
rs1060499612	C>G	Likely-pathogenic	Splice donor variant
rs1178306013	C>-	Pathogenic	Non coding transcript variant, coding sequence variant, 3 prime UTR variant, frameshift variant
rs1261058897	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained, genic downstream transcript variant
rs1554335461	C>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1554353948	C>T	Likely-pathogenic	Intron variant
rs1562774655	->CCGGGCAGCCACCTGTAATCTCC	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1562774778	A>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1562831765	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, stop gained
rs1584422832	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1584433525	A>-	Likely-pathogenic	5 prime UTR variant, frameshift variant, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001594	hsa-let-7b-5p	pSILAC	18668040
MIRT027664	hsa-miR-98-5p	Microarray	19088304
MIRT001594	hsa-let-7b-5p	Proteomics;Other	18668040
MIRT001594	hsa-let-7b-5p	CLASH	23622248
MIRT047732	hsa-miR-10a-5p	CLASH	23622248
MIRT045193	hsa-miR-186-5p	CLASH	23622248
MIRT442464	hsa-miR-605-5p	PAR-CLIP	22100165
MIRT442463	hsa-miR-4255	PAR-CLIP	22100165
MIRT442462	hsa-miR-96-3p	PAR-CLIP	22100165
MIRT442461	hsa-miR-142-3p	PAR-CLIP	22100165
MIRT442460	hsa-miR-3591-5p	PAR-CLIP	22100165
MIRT442464	hsa-miR-605-5p	PAR-CLIP	22100165
MIRT442463	hsa-miR-4255	PAR-CLIP	22100165
MIRT442462	hsa-miR-96-3p	PAR-CLIP	22100165
MIRT442461	hsa-miR-142-3p	PAR-CLIP	22100165
MIRT442460	hsa-miR-3591-5p	PAR-CLIP	22100165
MIRT1355282	hsa-miR-1254	CLIP-seq
MIRT1355283	hsa-miR-1305	CLIP-seq
MIRT1355284	hsa-miR-1912	CLIP-seq
MIRT1355285	hsa-miR-2113	CLIP-seq
MIRT1355286	hsa-miR-221	CLIP-seq
MIRT1355287	hsa-miR-222	CLIP-seq
MIRT1355288	hsa-miR-23a	CLIP-seq
MIRT1355289	hsa-miR-23b	CLIP-seq
MIRT1355290	hsa-miR-23c	CLIP-seq
MIRT1355291	hsa-miR-3116	CLIP-seq
MIRT1355292	hsa-miR-3173-3p	CLIP-seq
MIRT1355293	hsa-miR-3184	CLIP-seq
MIRT1355294	hsa-miR-335	CLIP-seq
MIRT1355295	hsa-miR-3646	CLIP-seq
MIRT1355296	hsa-miR-3653	CLIP-seq
MIRT1355297	hsa-miR-3658	CLIP-seq
MIRT1355298	hsa-miR-3659	CLIP-seq
MIRT1355299	hsa-miR-3662	CLIP-seq
MIRT1355300	hsa-miR-3690	CLIP-seq
MIRT1355301	hsa-miR-378	CLIP-seq
MIRT1355302	hsa-miR-378b	CLIP-seq
MIRT1355303	hsa-miR-378c	CLIP-seq
MIRT1355304	hsa-miR-378d	CLIP-seq
MIRT1355305	hsa-miR-378e	CLIP-seq
MIRT1355306	hsa-miR-378f	CLIP-seq
MIRT1355307	hsa-miR-378h	CLIP-seq
MIRT1355308	hsa-miR-378i	CLIP-seq
MIRT1355309	hsa-miR-422a	CLIP-seq
MIRT1355310	hsa-miR-423-5p	CLIP-seq
MIRT1355311	hsa-miR-4452	CLIP-seq
MIRT1355312	hsa-miR-4477a	CLIP-seq
MIRT1355313	hsa-miR-4489	CLIP-seq
MIRT1355314	hsa-miR-4717-3p	CLIP-seq
MIRT1355315	hsa-miR-4735-5p	CLIP-seq
MIRT1355316	hsa-miR-4768-3p	CLIP-seq
MIRT1355317	hsa-miR-4779	CLIP-seq
MIRT1355318	hsa-miR-498	CLIP-seq
MIRT1355319	hsa-miR-570	CLIP-seq
MIRT1355320	hsa-miR-665	CLIP-seq
MIRT1355321	hsa-miR-1298	CLIP-seq
MIRT1355322	hsa-miR-1915	CLIP-seq
MIRT1355323	hsa-miR-2116	CLIP-seq
MIRT1355324	hsa-miR-217	CLIP-seq
MIRT1355325	hsa-miR-4418	CLIP-seq
MIRT1355326	hsa-miR-4459	CLIP-seq
MIRT1355327	hsa-miR-4677-5p	CLIP-seq
MIRT1355328	hsa-miR-4726-3p	CLIP-seq
MIRT1355329	hsa-miR-4733-5p	CLIP-seq
MIRT1355317	hsa-miR-4779	CLIP-seq
MIRT1355330	hsa-miR-509-3-5p	CLIP-seq
MIRT1355331	hsa-miR-509-5p	CLIP-seq
MIRT1355320	hsa-miR-665	CLIP-seq
MIRT2329799	hsa-miR-101	CLIP-seq
MIRT2329800	hsa-miR-1244	CLIP-seq
MIRT2329801	hsa-miR-1263	CLIP-seq
MIRT2329802	hsa-miR-127-5p	CLIP-seq
MIRT2329803	hsa-miR-141	CLIP-seq
MIRT2329804	hsa-miR-144	CLIP-seq
MIRT2329805	hsa-miR-200a	CLIP-seq
MIRT1355286	hsa-miR-221	CLIP-seq
MIRT1355287	hsa-miR-222	CLIP-seq
MIRT2329806	hsa-miR-29a	CLIP-seq
MIRT2329807	hsa-miR-29b	CLIP-seq
MIRT2329808	hsa-miR-29c	CLIP-seq
MIRT1355293	hsa-miR-3184	CLIP-seq
MIRT2329809	hsa-miR-3194-3p	CLIP-seq
MIRT2329810	hsa-miR-325	CLIP-seq
MIRT2329811	hsa-miR-338-5p	CLIP-seq
MIRT2329812	hsa-miR-3663-3p	CLIP-seq
MIRT2329813	hsa-miR-3692	CLIP-seq
MIRT2329814	hsa-miR-3921	CLIP-seq
MIRT2329815	hsa-miR-3929	CLIP-seq
MIRT1355310	hsa-miR-423-5p	CLIP-seq
MIRT2329816	hsa-miR-4303	CLIP-seq
MIRT2329817	hsa-miR-4419b	CLIP-seq
MIRT2329818	hsa-miR-4427	CLIP-seq
MIRT2329819	hsa-miR-4478	CLIP-seq
MIRT1355313	hsa-miR-4489	CLIP-seq
MIRT2329820	hsa-miR-4517	CLIP-seq
MIRT2329821	hsa-miR-4653-5p	CLIP-seq
MIRT2329822	hsa-miR-4719	CLIP-seq
MIRT2329823	hsa-miR-4755-3p	CLIP-seq
MIRT1355316	hsa-miR-4768-3p	CLIP-seq
MIRT2329824	hsa-miR-4786-3p	CLIP-seq
MIRT2329825	hsa-miR-513b	CLIP-seq
MIRT2329826	hsa-miR-520d-5p	CLIP-seq
MIRT2329827	hsa-miR-524-5p	CLIP-seq
MIRT2329828	hsa-miR-582-5p	CLIP-seq
MIRT2329829	hsa-miR-600	CLIP-seq
MIRT1355320	hsa-miR-665	CLIP-seq
MIRT2329830	hsa-miR-767-5p	CLIP-seq
MIRT2329831	hsa-miR-802	CLIP-seq
MIRT1355329	hsa-miR-4733-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000514	Function	3-sulfino-L-alanine: proton, glutamate antiporter activity	IDA	11566871
GO:0000514	Function	3-sulfino-L-alanine: proton, glutamate antiporter activity	IEA
GO:0000515	Function	Aspartate:glutamate, proton antiporter activity	IDA	11566871
GO:0000515	Function	Aspartate:glutamate, proton antiporter activity	IEA
GO:0005313	Function	L-glutamate transmembrane transporter activity	IBA
GO:0005313	Function	L-glutamate transmembrane transporter activity	IEA
GO:0005509	Function	Calcium ion binding	IDA	10642534, 25410934
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	28514442, 33961781
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	10642534, 11566871
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IDA	11566871
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	ISS
GO:0005743	Component	Mitochondrial inner membrane	TAS
GO:0005886	Component	Plasma membrane	NAS	10642534
GO:0006094	Process	Gluconeogenesis	IEA
GO:0006754	Process	ATP biosynthetic process	IDA	12851387
GO:0006839	Process	Mitochondrial transport	NAS	10642534
GO:0015172	Function	Acidic amino acid transmembrane transporter activity	IEA
GO:0015183	Function	L-aspartate transmembrane transporter activity	IBA
GO:0015804	Process	Neutral amino acid transport	IEA
GO:0015810	Process	Aspartate transmembrane transport	IBA
GO:0015810	Process	Aspartate transmembrane transport	IDA	11566871
GO:0015810	Process	Aspartate transmembrane transport	IEA
GO:0015810	Process	Aspartate transmembrane transport	IEA
GO:0015813	Process	L-glutamate transmembrane transport	IBA
GO:0015813	Process	L-glutamate transmembrane transport	IDA	11566871
GO:0015813	Process	L-glutamate transmembrane transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0042802	Function	Identical protein binding	IDA	25410934
GO:0043490	Process	Malate-aspartate shuttle	IBA
GO:0043490	Process	Malate-aspartate shuttle	IDA	11566871
GO:0043490	Process	Malate-aspartate shuttle	IEA
GO:0043490	Process	Malate-aspartate shuttle	IEA
GO:0043490	Process	Malate-aspartate shuttle	IGI	37647199
GO:0045333	Process	Cellular respiration	IDA	12851387
GO:0046872	Function	Metal ion binding	IEA
GO:0051592	Process	Response to calcium ion	IDA	11566871
GO:0051592	Process	Response to calcium ion	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0070778	Process	L-aspartate transmembrane transport	IEA
GO:1902600	Process	Proton transmembrane transport	IEA

Other IDs

• MIM: 603859
• HGNC: 10983
• e!Ensembl: ENSG00000004864

Protein

• UniProt ID: Q9UJS0
• Protein name: Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial (Calcium-binding mitochondrial carrier protein Aralar2) (ARALAR-related gene 2) (ARALAR2) (Citrin) (Mitochondrial aspartate glutamate carrier 2) (Solute carrier family 25 member 13)
• Protein function: 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 (PubMed:11566871, PubMed:38945283). Also mediates the upt
• PDB: 4P5W
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00153	Mito_carr	325 → 423	Mitochondrial carrier protein	Family
  PF00153	Mito_carr	424 → 515	Mitochondrial carrier protein	Family
  PF00153	Mito_carr	516 → 611	Mitochondrial carrier protein	Family

• Tissue specificity: TISSUE SPECIFICITY: High levels in liver and low levels in kidney, pancreas, placenta, heart and brain. {ECO:0000269|PubMed:10369257, ECO:0000269|PubMed:10642534}.
• Sequence:

  MAAAKVALTKRADPAELRTIFLKYASIEKNGEFFMSPNDFVTRYLNIFGESQPNPKTVEL
  LSGVVDQTKDGLISFQEFVAFESVLCAPDALFMVAFQLFDKAGKGEVTFEDVKQVFGQTT
  IHQHIPFNWDSEFVQLHFGKERKRHLTYAEFTQFLLEIQLEHAKQAFVQRDNARTGRVTA
  IDFRDIMVTIRPHVLTPFVEECLVAAAGGTTSHQVSFSYFNGFNSLLNNMELIRKIYSTL
  AGTRKDVEVTKEEFVLAAQKFGQVTPMEVDILFQLADLYEPRGRMTLADIERIAPLEEGT
  LPFNLAEAQRQKASGDSARPVLLQVAESAYRFGLGSVAGAVGATAVYPIDLVKTRMQNQR
  STGSFVGELMYKNSFDCFKKVLRYEGFFGLYRGLLPQLLGVAPEKAIKLTVNDFVRDKFM
  HKDGSVPLAAEILAGGCAGGSQVIFTNPLEIVKIRLQVAGEITTGPRVSALSVVRDLGFF
  GIYKGAKACFLRDIPFSAIYFPCYAHVKASFANEDGQVSPGSLLLAGAIAGMPAASLVTP
  ADVIKTRLQVAARAGQTTYSGVIDCFRKILREEGPKALWKGAGARVFRSSPQFGVTLLTY
  ELLQRWFYIDFGGVKPMGSEPVPKSRINLPAPNPDHVGGYKLAVATFAGIENKFGLYLPL
  FKPSVSTSKAIGGGP

• Sequence length: 675

Pathways

Reactome:

Gluconeogenesis
Aspartate and asparagine metabolism

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Adult-onset citrullinemia type I	Pathogenic; Likely pathogenic	rs80338722, rs80338723, rs80338720, rs80338721, rs80338717	RCV006449350 RCV006449351 RCV006449362 RCV006449354 RCV006449355	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrin deficiency	Likely pathogenic; Pathogenic	rs771583670, rs781452100, rs1794574986, rs201168119, rs879255502, rs1794536022, rs758827458, rs2116650029, rs2116663520, rs2116717319, rs1562844289, rs2116815571, rs1798487766, rs1255908000, rs762925301, rs1794001446, rs2116939424, rs748094224, rs962082210, rs2116384695, rs1791532136, rs2116426311, rs780525233, rs761370420, rs1286193203, rs1794924933, rs773624358, rs1794541339, rs2116384200, rs2116939192, rs2116939236, rs2116939333, rs1799374421, rs2116481274, rs1012084121, rs1794540164, rs973986984, rs2116717136, rs762941850, rs2116482158, rs750225643, rs1254503252, rs2116656505, rs2116384455, rs756182703, rs534585904, rs2485541368, rs1323174734, rs1309471492, rs2485974254, rs2485894223, rs2485796243, rs2485829669, rs2485838622, rs572198981, rs80338722, rs80338725, rs80338719, rs80338723, rs80338726, rs2485894793, rs2485819162, rs2485839244, rs2485894532, rs2486089519, rs80338720, rs746155190, rs2485543139, rs1792048079, rs765919667, rs1562897434, rs758135569, rs1792814581, rs2485736833, rs1362890886, rs80338718, rs2486153684, rs2485729829, rs2486088642, rs2485894796, rs2485543530, rs59507540, rs2116648196, rs1396885141, rs571127452, rs2485542562, rs2485838385, rs80338721, rs80338724, rs80338715, rs80338727, rs80338729, rs80338716, rs80338717, rs763191789, rs1554335461, rs1562831765, rs1261058897, rs1178306013, rs764401478, rs768922690, rs1004549438, rs1312396424, rs1482630982, rs1796684525, rs1794918929, rs548769905, rs540149539, rs1269555090, rs1792801432, rs398122839	RCV001379885 RCV001379390 RCV001378096 RCV001388329 RCV001381428 RCV001384102 RCV001388981 RCV001386601 RCV001382118 RCV001390452 RCV001380173 RCV001387206 RCV001388982 RCV001381994 RCV002544257 RCV001990703 RCV001875306 RCV001991872 RCV001991665 RCV001902844 RCV001864775 RCV001908312 RCV001932041 RCV001911648 RCV001865130 RCV001902012 RCV001914350 RCV001958904 RCV001975186 RCV001944743 RCV001909497 RCV001926856 RCV001993119 RCV001978515 RCV002014726 RCV002007457 RCV002007458 RCV001960532 RCV001956177 RCV001906644 RCV001883822 RCV001963086 RCV001949548 RCV002051468 RCV001922242 RCV002643901 RCV003112193 RCV002635333 RCV002710448 RCV002802010 RCV002810747 RCV002861572 RCV002876391 RCV002876643 RCV002894722 RCV002895164 RCV000808307 RCV000822371 RCV001247797 RCV000796573 RCV001060497 RCV002932236 RCV002968018 RCV003012037 RCV003043693 RCV003040081 RCV003047000 RCV000344746 RCV001854929 RCV003581940 RCV005100226 RCV005100227 RCV003741356 RCV003741357 RCV003581987 RCV003581440 RCV003581441 RCV003581442 RCV003583075 RCV003582070 RCV003741529 RCV003741709 RCV003741735 RCV003741720 RCV003741988 RCV003742098 RCV003740882 RCV003741070 RCV003740920 RCV003842918 RCV003858810 RCV003879239 RCV001058684 RCV001378585 RCV001851978 RCV001217432 RCV002513147 RCV000815004 RCV000811639 RCV000556924 RCV000806593 RCV000543573 RCV003581706 RCV001221001 RCV000823111 RCV000791562 RCV000796684 RCV001044508 RCV003581770 RCV001067356 RCV001061179 RCV001040084 RCV001054372 RCV001041184 RCV001220237 RCV001203153 RCV001208433 RCV001202155 RCV001232042 RCV001854367	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
CITRIN DEFICIENCY, NEONATAL ONSET	Pathogenic; Likely pathogenic	rs80338722, rs80338726, rs80338720	RCV005234780 RCV005234781 RCV005235125	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Citrullinemia	Likely pathogenic; Pathogenic	rs1794574986, rs201168119, rs80338719, rs80338726, rs1311945646, rs80338724, rs80338716, rs763191789, rs758827458, rs962082210, rs1312396424, rs548769905, rs540149539, rs1269555090	RCV005606816 RCV005606823 RCV001826423 RCV001831516 RCV005610691 RCV001826486 RCV001831590 RCV001828382 RCV001834681 RCV001830599 RCV001832548 RCV001833784 RCV001833833 RCV001833772	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrullinemia type I	Likely pathogenic; Pathogenic	rs761370420	RCV000987930	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Citrullinemia type II	Pathogenic; Likely pathogenic	rs1794540164, rs973986984, rs1793999476, rs80338722, rs80338725, rs80338719, rs80338723, rs80338726, rs80338720, rs2485729429, rs534452813, rs80338721, rs80338729, rs80338717, rs1060499612, rs1312396424, rs548769905, rs398122839	RCV003331247 RCV003388066 RCV002266455 RCV000006369 RCV000006371 RCV000006372 RCV000006373 RCV000006374 RCV000239614 RCV003231042 RCV003324175 RCV001262833 RCV003230369 RCV000779548 RCV000477873 RCV003226430 RCV003155369 RCV000404137	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrullinemia, type II, adult-onset	Likely pathogenic; Pathogenic	rs771583670, rs781452100, rs201168119, rs879255502, rs758827458, rs2116717319, rs2116815571, rs762925301, rs1794001446, rs748094224, rs2116426311, rs780525233, rs1794924933, rs2116384200, rs1012084121, rs1794540164, rs973986984, rs762941850, rs1254503252, rs1793999476, rs534585904, rs1323174734, rs80338722, rs80338725, rs80338719, rs80338723, rs80338726, rs80338720, rs2485543774, rs746155190, rs2485729429, rs534452813, rs2485543139, rs779220022, rs2485792804, rs143181462, rs2485974086, rs2485543587, rs766044536, rs2485577175, rs1792048079, rs1794834161, rs2485543807, rs2485894614, rs2485792452, rs765919667, rs1477219779, rs2485542638, rs1562897434, rs2485791673, rs2485541466, rs1794000888, rs1431951130, rs2485577477, rs2485974252, rs2485792717, rs758135569, rs2485894721, rs2485837844, rs1562811734, rs2485791702, rs2485821259, rs1562831563, rs1363947528, rs2485819209, rs371781535, rs80338718, rs2485974231, rs1311945646, rs2116382630, rs1794774221, rs2486226043, rs2485973971, rs80338721, rs80338724, rs80338715, rs80338727, rs80338729, rs80338716, rs80338717, rs1060499612, rs1562831765, rs962082210, rs1261058897, rs761370420, rs768922690, rs1004549438, rs1312396424, rs1482630982, rs548769905, rs540149539, rs398122839	RCV003473920 RCV003473918 RCV004570967 RCV004570941 RCV003469750 RCV003469774 RCV005038200 RCV003475087 RCV003471206 RCV004571933 RCV002503498 RCV002503416 RCV003470969 RCV003475253 RCV003471113 RCV003475207 RCV003471124 RCV004571742 RCV003475256 RCV005032207 RCV003465985 RCV003475406 RCV002259301 RCV002259302 RCV003472982 RCV003472983 RCV003472984 RCV005045128 RCV002259321 RCV003466020 RCV004567798 RCV005047477 RCV005036739 RCV003472800 RCV003472801 RCV003472802 RCV003466384 RCV003466385 RCV003466386 RCV003466387 RCV003466388 RCV003466389 RCV003466390 RCV003466391 RCV003466392 RCV003466393 RCV003466394 RCV003466395 RCV003466396 RCV003466398 RCV003472803 RCV003472804 RCV003472805 RCV003472806 RCV003472807 RCV003472808 RCV003472809 RCV003472810 RCV003472811 RCV003472812 RCV003472813 RCV003472814 RCV003472815 RCV003472817 RCV003472818 RCV003472819 RCV003472820 RCV003472821 RCV004574098 RCV005038614 RCV004573607 RCV004573608 RCV004573609 RCV004573610 RCV004573611 RCV004573612 RCV002259307 RCV003473112 RCV003473113 RCV003473114 RCV002496427 RCV002496428 RCV002259308 RCV004568140 RCV005034068 RCV004569412 RCV003465657 RCV003467515 RCV003473532 RCV003473552 RCV005047282 RCV003473677 RCV003467721 RCV003473738 RCV003469344 RCV003474671	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Malignant lymphoma, large B-cell, diffuse	Pathogenic	rs80338720	RCV005868120	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Melanoma	Likely pathogenic; Pathogenic	rs761370420	RCV005912160	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neonatal intrahepatic cholestasis due to citrin deficiency	Likely pathogenic; Pathogenic	rs2116815571, rs2116426311, rs780525233, rs1012084121, rs973986984, rs762941850, rs2486089007, rs2485541958, rs1793999476, rs763272772, rs80338722, rs80338725, rs80338719, rs80338723, rs80338726, rs80338720, rs746155190, rs879255504, rs2485729429, rs534452813, rs143181462, rs2485543807, rs1794001446, rs80338721, rs80338724, rs80338715, rs80338727, rs80338729, rs80338716, rs80338717, rs1060499612, rs758827458, rs1562774655, rs1562831765, rs962082210, rs768922690, rs1584422832, rs1584433525, rs1004549438, rs1312396424, rs1792048079, rs540149539, rs1319034578, rs398122839	RCV005038200 RCV002503498 RCV002503416 RCV005031985 RCV002479573 RCV005032016 RCV002508347 RCV002509767 RCV005032207 RCV002285225 RCV000006370 RCV001004526 RCV001004531 RCV004786241 RCV000006375 RCV005045128 RCV000006368 RCV000239387 RCV000239388 RCV005047477 RCV005036739 RCV005047616 RCV005036822 RCV005038614 RCV005031445 RCV000020699 RCV000020700 RCV000020703 RCV000020704 RCV000020705 RCV000020707 RCV000477873 RCV005034068 RCV000721963 RCV000721964 RCV005036048 RCV001004528 RCV001004529 RCV001004530 RCV005047282 RCV004584421 RCV001376648 RCV002508296 RCV001376647 RCV000077782	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Short-rib thoracic dysplasia 6 with or without polydactyly	Likely pathogenic	rs748094224	RCV005645353	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SLC25A13-related disorder	Likely pathogenic; Pathogenic	rs780525233, rs1794541339, rs80338722, rs80338725, rs80338726, rs80338720, rs80338717, rs761370420, rs1792048079	RCV004743606 RCV003401975 RCV004742216 RCV004742217 RCV004742218 RCV003417766 RCV003924850 RCV003936241 RCV003405262	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRIN DEFICIENCY, ADOLESCENT OR ADULT ONSET	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRIN DEFICIENCY, NEONATAL OR INFANTILE ONSET	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRULLINEMIA TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRULLINEMIA, TYPE II, NEONATAL-ONSET	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult-onset citrullinemia type 2	Citrullinemia	CLINVAR_DG	10369257, 11281457, 12424587, 14680984, 15050970, 17880783, 18392553, 19036621, 19470249, 21134364, 21424115, 21507300, 24161253, 24586645		★☆☆☆☆ Found in Text Mining only
Adult-onset citrullinemia type 2	Citrullinemia	BEFREE	11153906, 11281457, 11793471, 12111366, 12424587, 12512993, 12602510, 12692712, 14680976, 14680984, 14701727, 15050970, 15295082, 15542392, 16059747, 16311094, 16449956, 17000460, 17092749, 17982687, 18162705, 18392553, 18487280, 18620775, 19413723, 20927635, 21134364, 21161389, 21424115, 21470889, 21914561, 22095253, 22277121, 23053473, 23067347, 24161253, 24586645, 25110155, 25216257, 25533124, 26109823, 27405544, 27829683, 29787821, 30181955, 30591617, 30708027, 30862943, 30887117, 31255436, 31462712, 31809266		★☆☆☆☆ Found in Text Mining only
Adult-onset citrullinemia type 2	Citrullinemia	GENOMICS_ENGLAND_DG	12424587, 27604308		★☆☆☆☆ Found in Text Mining only
Adult-onset citrullinemia type 2	Citrullinemia	CTD_human_DG	16449956		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Blood coagulation disorder	Pubtator	37146272	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	12512993, 14606711, 17000460, 21767414, 30995827	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cholestasis	Cholestasis	BEFREE	11793471		★☆☆☆☆ Found in Text Mining only
Cholestasis Intrahepatic	Intrahepatic cholestasis	Pubtator	18162705, 20458766, 22892490, 23067347, 23901231, 27706244, 33497767, 37146272	Associate	★☆☆☆☆ Found in Text Mining only
Cholestasis, progressive familial intrahepatic 1	Intrahepatic cholestasis	BEFREE	18487280		★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Citrin deficiency	Citrin Deficiency	CLINVAR_DG	10369257, 12512993, 14680984, 19036621, 21134364, 21507300, 22710133, 23022256, 24586645, 27405544, 27577219		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrin deficiency	Citrin Deficiency	BEFREE	11793471, 12111366, 12692712, 14680984, 15295082, 16059747, 17000460, 17092749, 17982687, 18392553, 18487280, 19413723, 20927635, 21161389, 21424115, 22095253, 22277121, 24161253, 24586645, 25110155, 25216257, 26109823, 27405544, 27829683, 29787821, 30181955, 30591617, 30708027, 30862943, 30887117, 31255436, 31809266		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrullinemia	Citrullinemia	LHGDN	12111366, 16278034, 16928234, 17000460		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrullinemia	Citrullinemia	BEFREE	12692712, 17000460, 19413723, 21161389, 24508627		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrullinemia	Citrullinemia	Pubtator	17000460, 22892490	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Citrullinemia Type 1	Citrullinemia	BEFREE	12692712		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Citrullinemia type II	Citrullinemia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
CITRULLINEMIA, TYPE II, NEONATAL-ONSET	Citrullinemia	BEFREE	11793471, 14680984, 15295082, 15542392, 16059747, 16737877, 17982687, 18162705, 18392553, 19185551, 20200759, 20927635, 21134364, 21914561, 22277121, 22710133, 23053473, 23067347, 27127784, 27405544, 27779681, 28516797, 31607264, 31809266		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRULLINEMIA, TYPE II, NEONATAL-ONSET	Citrullinemia	UNIPROT_DG	11793471		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRULLINEMIA, TYPE II, NEONATAL-ONSET	Citrullinemia	GENOMICS_ENGLAND_DG	12424587, 27604308		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRULLINEMIA, TYPE II, NEONATAL-ONSET	Citrullinemia	CLINVAR_DG	21507300, 24327139		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CITRULLINEMIA, TYPE II, NEONATAL-ONSET	Citrullinemia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cleft Lip with or without Cleft Palate	Cleft Lip With Or Without Cleft Palate	BEFREE	20739017		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	27924922		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	27924922	Associate	★☆☆☆☆ Found in Text Mining only
Conjugated hyperbilirubinemia	Conjugated hyperbilirubinemia	BEFREE	25381944		★☆☆☆☆ Found in Text Mining only
Delayed menarche	Delayed menarche	HPO_DG			★☆☆☆☆ Found in Text Mining only
Delirium	Delirium	BEFREE	29787821		★☆☆☆☆ Found in Text Mining only
Delirium	Delirium	HPO_DG			★☆☆☆☆ Found in Text Mining only
Delusions	Delusions	HPO_DG			★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	16449956		★☆☆☆☆ Found in Text Mining only
Esophageal Atresia	Esophageal atresia	Pubtator	25216257	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	16737877, 18620775		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty liver	Pubtator	17000460, 22892490, 23067347, 34684069	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	37047726	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	37047726	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hallucinations	Hallucinations	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hepatic Encephalopathy	Hepatic encephalopathy	Pubtator	21908947	Associate	★☆☆☆☆ Found in Text Mining only
Hepatic Encephalopathy	Hepatic Encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperammonemia	Hyperammonemia	Pubtator	12512993, 25533124	Associate	★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia	Hyperbilirubinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperferritinemia	Hyperferritinemia	Pubtator	22892490	Associate	★☆☆☆☆ Found in Text Mining only
Hyperlysinemias	Hyperlysinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoalbuminemia	Hypoalbuminemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	Pubtator	28516797, 37146272	Associate	★☆☆☆☆ Found in Text Mining only
Hypoproteinemia	Hypoproteinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inborn Errors of Metabolism	Inborn Errors Of Metabolism	BEFREE	19185551		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	12512993	Associate	★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholestasis	Intrahepatic Cholestasis	BEFREE	12692712, 15295082, 15542392, 16059747, 16311094, 20458766, 20927635, 21161389, 21914561, 23901231		★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholestasis	Intrahepatic Cholestasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Jaundice, Obstructive	Jaundice	BEFREE	23067347		★☆☆☆☆ Found in Text Mining only
Ketonuria	Ketonuria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	17000460, 21134364, 21470889		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	Pubtator	22095253, 37146272	Associate	★☆☆☆☆ Found in Text Mining only
Manic	Manic Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	35607442	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	28516797		★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia	Methylmalonic acidemia	Pubtator	33514801	Associate	★☆☆☆☆ Found in Text Mining only
Neonatal intrahepatic cholestasis due to citrin deficiency	Intrahepatic Cholestasis	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neoplasms	Neoplasms	BEFREE	21470889, 27924922		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	18620775		★☆☆☆☆ Found in Text Mining only
Pancreatic Diseases	Pancreatic Diseases	BEFREE	19036621		★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive intrahepatic cholestasis (disorder)	Intrahepatic Cholestasis	BEFREE	18487280		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	16737877, 17000460, 18620775		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	37047726	Associate	★☆☆☆☆ Found in Text Mining only
Tyrosinemias	Tyrosinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only