CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase)

Gene

• Entrez ID: 790
• Gene name: Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
• Gene symbol: CAD
• Synonyms (NCBI Gene): CDG1Z, DEE50, EIEE50, GATD4
• Chromosome: 2
• Chromosome location: 2p23.3
• Summary: The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynth

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs62130681	C>A,T	Pathogenic	Coding sequence variant, stop gained, synonymous variant
rs139332887	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs202227357	A>G	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs751610198	T>G	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs763410987	G>A	Pathogenic	Coding sequence variant, missense variant
rs769567624	G>A	Pathogenic	Intron variant, splice acceptor variant
rs1019263242	TTCTCCAAGGCCC>-	Pathogenic	Frameshift variant, coding sequence variant
rs1057519262	C>T	Likely-pathogenic	Intron variant
rs1085307810	GACA>-	Pathogenic	Coding sequence variant, frameshift variant
rs1572423883	C>T	Pathogenic	Coding sequence variant, genic upstream transcript variant, stop gained
rs1572426165	TG>-	Likely-pathogenic	Coding sequence variant, upstream transcript variant, frameshift variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023598	hsa-miR-1-3p	Proteomics	18668040
MIRT025309	hsa-miR-34a-5p	Proteomics	21566225
MIRT028960	hsa-miR-26b-5p	Microarray	19088304
MIRT049353	hsa-miR-92a-3p	CLASH	23622248
MIRT045293	hsa-miR-186-5p	CLASH	23622248
MIRT044218	hsa-miR-301a-3p	CLASH	23622248
MIRT043489	hsa-miR-331-3p	CLASH	23622248
MIRT040681	hsa-miR-92b-3p	CLASH	23622248
MIRT037941	hsa-miR-505-5p	CLASH	23622248
MIRT037941	hsa-miR-505-5p	CLASH	23622248
MIRT037845	hsa-miR-455-3p	CLASH	23622248
MIRT052821	hsa-miR-3200-3p	CLASH	23622248
MIRT484459	hsa-miR-3200-5p	PAR-CLIP	23592263
MIRT484458	hsa-miR-6872-3p	PAR-CLIP	23592263
MIRT484457	hsa-miR-4649-3p	PAR-CLIP	23592263
MIRT484456	hsa-miR-7162-3p	PAR-CLIP	23592263
MIRT484454	hsa-miR-5008-5p	PAR-CLIP	23592263
MIRT484455	hsa-miR-6089	PAR-CLIP	23592263
MIRT484453	hsa-miR-4758-3p	PAR-CLIP	23592263
MIRT484452	hsa-miR-874-5p	PAR-CLIP	23592263
MIRT480212	hsa-miR-4426	PAR-CLIP	23592263
MIRT480211	hsa-miR-4647	PAR-CLIP	23592263
MIRT480210	hsa-miR-4662b	PAR-CLIP	23592263
MIRT480209	hsa-miR-18a-5p	PAR-CLIP	23592263
MIRT480208	hsa-miR-18b-5p	PAR-CLIP	23592263
MIRT480207	hsa-miR-4735-3p	PAR-CLIP	23592263
MIRT480206	hsa-miR-552-3p	PAR-CLIP	23592263
MIRT480204	hsa-miR-4463	PAR-CLIP	23592263
MIRT480205	hsa-miR-3675-5p	PAR-CLIP	23592263
MIRT480203	hsa-miR-4494	PAR-CLIP	23592263
MIRT480202	hsa-miR-4699-5p	PAR-CLIP	23592263
MIRT480201	hsa-miR-4771	PAR-CLIP	23592263
MIRT480200	hsa-miR-873-5p	PAR-CLIP	23592263
MIRT480199	hsa-miR-1286	PAR-CLIP	23592263
MIRT480198	hsa-miR-4722-5p	PAR-CLIP	23592263
MIRT480197	hsa-miR-486-3p	PAR-CLIP	23592263
MIRT480196	hsa-miR-943	PAR-CLIP	23592263
MIRT480195	hsa-let-7a-2-3p	PAR-CLIP	23592263
MIRT480194	hsa-let-7g-3p	PAR-CLIP	23592263
MIRT480193	hsa-miR-4477b	PAR-CLIP	23592263
MIRT480192	hsa-miR-7856-5p	PAR-CLIP	23592263
MIRT037845	hsa-miR-455-3p	PAR-CLIP	27292025
MIRT049353	hsa-miR-92a-3p	PAR-CLIP	27292025
MIRT040681	hsa-miR-92b-3p	PAR-CLIP	27292025
MIRT484459	hsa-miR-3200-5p	PAR-CLIP	23592263
MIRT484458	hsa-miR-6872-3p	PAR-CLIP	23592263
MIRT484457	hsa-miR-4649-3p	PAR-CLIP	23592263
MIRT484456	hsa-miR-7162-3p	PAR-CLIP	23592263
MIRT484454	hsa-miR-5008-5p	PAR-CLIP	23592263
MIRT484455	hsa-miR-6089	PAR-CLIP	23592263
MIRT484453	hsa-miR-4758-3p	PAR-CLIP	23592263
MIRT484452	hsa-miR-874-5p	PAR-CLIP	23592263
MIRT480212	hsa-miR-4426	PAR-CLIP	23592263
MIRT480211	hsa-miR-4647	PAR-CLIP	23592263
MIRT480210	hsa-miR-4662b	PAR-CLIP	23592263
MIRT480209	hsa-miR-18a-5p	PAR-CLIP	23592263
MIRT480208	hsa-miR-18b-5p	PAR-CLIP	23592263
MIRT480207	hsa-miR-4735-3p	PAR-CLIP	23592263
MIRT480206	hsa-miR-552-3p	PAR-CLIP	23592263
MIRT480204	hsa-miR-4463	PAR-CLIP	23592263
MIRT480205	hsa-miR-3675-5p	PAR-CLIP	23592263
MIRT480203	hsa-miR-4494	PAR-CLIP	23592263
MIRT480202	hsa-miR-4699-5p	PAR-CLIP	23592263
MIRT480201	hsa-miR-4771	PAR-CLIP	23592263
MIRT480200	hsa-miR-873-5p	PAR-CLIP	23592263
MIRT480199	hsa-miR-1286	PAR-CLIP	23592263
MIRT480198	hsa-miR-4722-5p	PAR-CLIP	23592263
MIRT480197	hsa-miR-486-3p	PAR-CLIP	23592263
MIRT480196	hsa-miR-943	PAR-CLIP	23592263
MIRT480195	hsa-let-7a-2-3p	PAR-CLIP	23592263
MIRT480194	hsa-let-7g-3p	PAR-CLIP	23592263
MIRT480193	hsa-miR-4477b	PAR-CLIP	23592263
MIRT480192	hsa-miR-7856-5p	PAR-CLIP	23592263
MIRT858432	hsa-miR-1207-3p	CLIP-seq
MIRT858433	hsa-miR-18a	CLIP-seq
MIRT858434	hsa-miR-18b	CLIP-seq
MIRT858435	hsa-miR-1913	CLIP-seq
MIRT858436	hsa-miR-2861	CLIP-seq
MIRT858437	hsa-miR-296-5p	CLIP-seq
MIRT858438	hsa-miR-324-3p	CLIP-seq
MIRT858439	hsa-miR-338-3p	CLIP-seq
MIRT858440	hsa-miR-3612	CLIP-seq
MIRT858441	hsa-miR-4266	CLIP-seq
MIRT858442	hsa-miR-4313	CLIP-seq
MIRT858443	hsa-miR-4530	CLIP-seq
MIRT858444	hsa-miR-4695-5p	CLIP-seq
MIRT858445	hsa-miR-4779	CLIP-seq
MIRT858446	hsa-miR-502-5p	CLIP-seq
MIRT858447	hsa-miR-552	CLIP-seq
MIRT858448	hsa-miR-595	CLIP-seq
MIRT858449	hsa-miR-646	CLIP-seq
MIRT858450	hsa-miR-648	CLIP-seq
MIRT858451	hsa-miR-650	CLIP-seq
MIRT1954935	hsa-miR-198	CLIP-seq
MIRT858439	hsa-miR-338-3p	CLIP-seq
MIRT1954936	hsa-miR-3616-5p	CLIP-seq
MIRT1954937	hsa-miR-3647-5p	CLIP-seq
MIRT1954938	hsa-miR-3662	CLIP-seq
MIRT1954939	hsa-miR-3925-3p	CLIP-seq
MIRT1954940	hsa-miR-4293	CLIP-seq
MIRT1954941	hsa-miR-4795-5p	CLIP-seq
MIRT1954942	hsa-miR-520a-5p	CLIP-seq
MIRT1954943	hsa-miR-525-5p	CLIP-seq
MIRT1954944	hsa-miR-573	CLIP-seq
MIRT858448	hsa-miR-595	CLIP-seq
MIRT2192528	hsa-miR-3065-3p	CLIP-seq
MIRT2192529	hsa-miR-3126-3p	CLIP-seq
MIRT2192530	hsa-miR-3607-5p	CLIP-seq
MIRT1954936	hsa-miR-3616-5p	CLIP-seq
MIRT1954937	hsa-miR-3647-5p	CLIP-seq
MIRT1954941	hsa-miR-4795-5p	CLIP-seq
MIRT1954944	hsa-miR-573	CLIP-seq
MIRT858448	hsa-miR-595	CLIP-seq
MIRT2192531	hsa-miR-610	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HDAC2	Unknown	14559996
MYC	Unknown	10931841;17706770
SMARCA4	Unknown	14559996

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001889	Process	Liver development	IEA
GO:0003824	Function	Catalytic activity	IEA
GO:0004070	Function	Aspartate carbamoyltransferase activity	IBA
GO:0004070	Function	Aspartate carbamoyltransferase activity	IEA
GO:0004070	Function	Aspartate carbamoyltransferase activity	ISS
GO:0004087	Function	Carbamoyl-phosphate synthase (ammonia) activity	IEA
GO:0004088	Function	Carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	IBA
GO:0004088	Function	Carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	IEA
GO:0004088	Function	Carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	ISS
GO:0004151	Function	Dihydroorotase activity	IBA
GO:0004151	Function	Dihydroorotase activity	IDA	24332717
GO:0004151	Function	Dihydroorotase activity	IEA
GO:0004151	Function	Dihydroorotase activity	ISS
GO:0004359	Function	Glutaminase activity	IEA
GO:0004672	Function	Protein kinase activity	ISS
GO:0005515	Function	Protein binding	IPI	15161933, 35271311, 35709258
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	ISS
GO:0005634	Component	Nucleus	IDA	15890648
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA	15890648
GO:0005829	Component	Cytosol	TAS
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	IBA
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	IDA	24332717
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	IEA
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	ISS
GO:0006221	Process	Pyrimidine nucleotide biosynthetic process	IEA
GO:0006225	Process	UDP biosynthetic process	IDA	25678555
GO:0006228	Process	UTP biosynthetic process	IEA
GO:0006520	Process	Amino acid metabolic process	IEA
GO:0006541	Process	Glutamine metabolic process	IBA
GO:0006541	Process	Glutamine metabolic process	IEA
GO:0006541	Process	Glutamine metabolic process	ISS
GO:0006796	Process	Phosphate-containing compound metabolic process	IEA
GO:0006805	Process	Xenobiotic metabolic process	IEA
GO:0007507	Process	Heart development	IEA
GO:0007565	Process	Female pregnancy	IEA
GO:0007595	Process	Lactation	IEA
GO:0008270	Function	Zinc ion binding	IDA	24332717
GO:0014075	Process	Response to amine	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016363	Component	Nuclear matrix	IDA	9525610
GO:0016597	Function	Amino acid binding	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016743	Function	Carboxyl- or carbamoyltransferase activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016810	Function	Hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	IEA
GO:0016812	Function	Hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0019240	Process	Citrulline biosynthetic process	IEA
GO:0019899	Function	Enzyme binding	IPI	15326225
GO:0031000	Process	Response to caffeine	IEA
GO:0031100	Process	Animal organ regeneration	IEA
GO:0032868	Process	Response to insulin	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0033574	Process	Response to testosterone	IEA
GO:0042594	Process	Response to starvation	IEA
GO:0042802	Function	Identical protein binding	IEA
GO:0042802	Function	Identical protein binding	IPI	24332717
GO:0042802	Function	Identical protein binding	ISS
GO:0042995	Component	Cell projection	IEA
GO:0042995	Component	Cell projection	ISS
GO:0043025	Component	Neuronal cell body	IEA
GO:0043025	Component	Neuronal cell body	ISS
GO:0043195	Component	Terminal bouton	IEA
GO:0043195	Component	Terminal bouton	ISS
GO:0044205	Process	'de novo' UMP biosynthetic process	IDA	25678555
GO:0044205	Process	'de novo' UMP biosynthetic process	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051414	Process	Response to cortisol	IEA
GO:0055086	Process	Nucleobase-containing small molecule metabolic process	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0070335	Function	Aspartate binding	ISS
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IEA
GO:0071466	Process	Cellular response to xenobiotic stimulus	IEA
GO:0072528	Process	Pyrimidine-containing compound biosynthetic process	IEA

Other IDs

• MIM: 114010
• HGNC: 1424
• e!Ensembl: ENSG00000084774

Protein

• UniProt ID: P27708
• Protein name: Multifunctional protein CAD (Carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase) [Includes: Glutamine-dependent carbamoyl phosphate synthase (EC 6.3.5.5); Glutamine amidotransferase (GATase) (GLNase) (EC 3.5.1.2); Ammonium-dependen
• Protein function: Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3).
• PDB: 4BY3, 4C6B, 4C6C, 4C6D, 4C6E, 4C6F, 4C6I, 4C6J, 4C6K, 4C6L, 4C6M, 4C6N, 4C6O, 4C6P, 4C6Q, 5G1N, 5G1O, 5G1P, 5YNZ, 6HFD, 6HFE, 6HFF, 6HFH, 6HFI, 6HFJ, 6HFK, 6HFL, 6HFN, 6HFP, 6HFQ, 6HFR, 6HFS, 6HFU, 6HG1, 8GVZ, 8GW0, 8PBE, 8PBG, 8PBH, 8PBI, 8PBJ, 8PBK, 8PBM, 8PBN, 8PBP, 8PBQ, 8PBR, 8PBS, 8PBT, 8PBU, 9FS1
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00988	CPSase_sm_chain	1 → 138	Carbamoyl-phosphate synthase small chain, CPSase domain	Domain
  PF00117	GATase	179 → 356	Glutamine amidotransferase class-I	Domain
  PF02786	CPSase_L_D2	514 → 718	Carbamoyl-phosphate synthase L chain, ATP binding domain	Domain
  PF02787	CPSase_L_D3	800 → 881	Carbamoyl-phosphate synthetase large chain, oligomerisation domain	Domain
  PF02786	CPSase_L_D2	1047 → 1250	Carbamoyl-phosphate synthase L chain, ATP binding domain	Domain
  PF02142	MGS	1327 → 1428	MGS-like domain	Domain
  PF01979	Amidohydro_1	1462 → 1745	Amidohydrolase family	Domain
  PF02729	OTCace_N	1924 → 2065	Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain	Domain
  PF00185	OTCace	2071 → 2221	Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain	Domain

• Sequence:

  MAALVLEDGSVLRGQPFGAAVSTAGEVVFQTGMVGYPEALTDPSYKAQILVLTYPLIGNY
  GIPPDEMDEFGLCKWFESSGIHVAALVVGECCPTPSHWSATRTLHEWLQQHGIPGLQGVD
  TRELTKKLREQGSLLGKLVQNGTEPSSLPFLDPNARPLVPEVSIKTPRVFNTGGAPRILA
  LDCGLKYNQIRCLCQRGAEVTVVPWDHALDSQEYEGLFLSNGPGDPASYPSVVSTLSRVL
  SEPNPRPVFGICLGHQLLALAIGAKTYKMRYGNRGHNQPCLLVGSGRCFLTSQNHGFAVE
  TDSLPADWAPLFTNANDGSNEGIVHNSLPFFSVQFHPEHQAGPSDMELLFDIFLETVKEA
  TAGNPGGQTVRERLTERLCPPGIPTPGSGLPPPRKVLILGSGGLSIGQAGEFDYSGSQAI
  KALKEENIQTLLINPNIATVQTSQGLADKVYFLPITPHYVTQVIRNERPDGVLLTFGGQT
  ALNCGVELTKAGVLARYGVRVLGTPVETIELTEDRRAFAARMAEIGEHVAPSEAANSLEQ
  AQAAAERLGYPVLVRAAFALGGLGSGFASNREELSALVAPAFAHTSQVLVDKSLKGWKEI
  EYEVVRDAYGNCVTVCNMENLDPLGIHTGESIVVAPSQTLNDREYQLLRQTAIKVTQHLG
  IVGECNVQYALNPESEQYYIIEVNARLSRSSALASKATGYPLAYVAAKLALGIPLPELRN
  SVTGGTAAFEPSVDYCVVKIPRWDLSKFLRVSTKIGSCMKSVGEVMGIGRSFEEAFQKAL
  RMVDENCVGFDHTVKPVSDMELETPTDKRIFVVAAALWAGYSVDRLYELTRIDRWFLHRM
  KRIIAHAQLLEQHRGQPLPPDLLQQAKCLGFSDKQIALAVLSTELAVRKLRQELGICPAV
  KQIDTVAAEWPAQTNYLYLTYWGTTHDLTFRTPHVLVLGSGVYRIGSSVEFDWCAVGCIQ
  QLRKMGYKTIMVNYNPETVSTDYDMCDRLYFDEISFEVVMDIYELENPEGVILSMGGQLP
  NNMAMALHRQQCRVLGTSPEAIDSAENRFKFSRLLDTIGISQPQWRELSDLESARQFCQT
  VGYPCVVRPSYVLSGAAMNVAYTDGDLERFLSSAAAVSKEHPVVISKFIQEAKEIDVDAV
  ASDGVVAAIAISEHVENAGVHSGDATLVTPPQDITAKTLERIKAIVHAVGQELQVTGPFN
  LQLIAKDDQLKVIECNVRVSRSFPFVSKTLGVDLVALATRVIMGEEVEPVGLMTGSGVVG
  VKVPQFSFSRLAGADVVLGVEMTSTGEVAGFGESRCEAYLKAMLSTGFKIPKKNILLTIG
  SYKNKSELLPTVRLLESLGYSLYASLGTADFYTEHGVKVTAVDWHFEEAVDGECPPQRSI
  LEQLAEKNFELVINLSMRGAGGRRLSSFVTKGYRTRRLAADFSVPLIIDIKCTKLFVEAL
  GQIGPAPPLKVHVDCMTSQKLVRLPGLIDVHVHLREPGGTHKEDFASGTAAALAGGITMV
  CAMPNTRPPIIDAPALALAQKLAEAGARCDFALFLGASSENAGTLGTVAGSAAGLKLYLN
  ETFSELRLDSVVQWMEHFETWPSHLPIVAHAEQQTVAAVLMVAQLTQRSVHICHVARKEE
  ILLIKAAKARGLPVTCEVAPHHLFLSHDDLERLGPGKGEVRPELGSRQDVEALWENMAVI
  DCFASDHAPHTLEEKCGSRPPPGFPGLETMLPLLLTAVSEGRLSLDDLLQRLHHNPRRIF
  HLPPQEDTYVEVDLEHEWTIPSHMPFSKAHWTPFEGQKVKGTVRRVVLRGEVAYIDGQVL
  VPPGYGQDVRKWPQGAVPQLPPSAPATSEMTTTPERPRRGIPGLPDGRFHLPPRIHRASD
  PGLPAEEPKEKSSRKVAEPELMGTPDGTCYPPPPVPRQASPQNLGTPGLLHPQTSPLLHS
  LVGQHILSVQQFTKDQMSHLFNVAHTLRMMVQKERSLDILKGKVMASMFYEVSTRTSSSF
  AAAMARLGGAVLSFSEATSSVQKGESLADSVQTMSCYADVVVLRHPQPGAVELAAKHCRR
  PVINAGDGVGEHPTQALLDIFTIREELGTVNGMTITMVGDLKHGRTVHSLACLLTQYRVS
  LRYVAPPSLRMPPTVRAFVASRGTKQEEFESIEEALPDTDVLYMTRIQKERFGSTQEYEA
  CFGQFILTPHIMTRAKKKMVVMHPMPRVNEISVEVDSDPRAAYFRQAENGMYIRMALLAT
  VLGRF

• Sequence length: 2225

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
Developmental and epileptic encephalopathy, 50	Likely pathogenic; Pathogenic	rs2148080342, rs1475014505, rs1159635090, rs769567624, rs2465293335, rs751610198, rs1057519262, rs62130681, rs139332887, rs1572423883, rs1676249686, rs1676113645	RCV001420666 RCV002279765 RCV005023404 RCV000185620 RCV004594904 RCV000415540 RCV000415584 RCV000415514 RCV000986606 RCV000986604 RCV001196647 RCV005029846	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile epileptic dyskinetic encephalopathy	Likely pathogenic; Pathogenic	rs2465322898, rs139332887	RCV002302513 RCV001778976	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian serous cystadenocarcinoma	Likely pathogenic	rs757585784	RCV005930230	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pancreatic adenocarcinoma	Likely pathogenic	rs2465306442	RCV005930648	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA, HYPOPLASTIC, CONGENITAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA, SICKLE CELL	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BETA THALASSEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BETA-THALASSEMIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CAD-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARBAMOYL-PHOSPHATE SYNTHETASE 2, ASPARTATE TRANSCARBAMYLASE, AND DIHYDROOROTASE CONGENITAL DISORDER OF GLYCOSYLATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital anomaly of face	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CONGENITAL HYPOPLASTIC ANEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONSTITUTIONAL APLASTIC ANEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary artery disease, autosomal dominant 2	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 50	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Familial cancer of breast	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Meniere disease	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Nonpapillary renal cell carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPHEROCYTOSIS, HEREDITARY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations