TCOF1 (treacle ribosome biogenesis factor 1)

Gene

• Entrez ID: 6949
• Gene name: Treacle ribosome biogenesis factor 1
• Gene symbol: TCOF1
• Synonyms (NCBI Gene): MFD1, TCS, TCS1, treacle
• Chromosome: 5
• Chromosome location: 5q32-q33.1
• Summary: This gene encodes a nucleolar protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins sy

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28941769	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs119470016	C>T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs119470017	C>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant, genic downstream transcript variant
rs148367422	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, genic downstream transcript variant
rs150637771	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs377241141	G>T	Likely-pathogenic	Intron variant, non coding transcript variant, coding sequence variant, stop gained
rs528897827	GATCTGAAAGTGAGGAGG>-	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant, non coding transcript variant, coding sequence variant, inframe deletion
rs587776580	->A	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs587776581	ATAC>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs587776582	AAGAA>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant
rs587776583	AGAG>-,AG	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs587776584	AAGGTGAGTGGGACTGCC>-	Pathogenic	Non coding transcript variant, coding sequence variant, splice donor variant, intron variant
rs587776585	AAAAA>-,AAA,AAAA,AAAAAA	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant
rs587777314	->G	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, genic downstream transcript variant
rs748805008	C>A,G,T	Pathogenic, likely-pathogenic	Intron variant, stop gained, missense variant, non coding transcript variant, synonymous variant, coding sequence variant
rs764314276	G>A	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs769931291	C>G,T	Pathogenic	Coding sequence variant, stop gained, missense variant, non coding transcript variant
rs786205575	C>T	Likely-pathogenic	Coding sequence variant, intron variant, non coding transcript variant, stop gained
rs797046037	CA>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs886041506	G>A	Pathogenic	Splice donor variant
rs886041672	TG>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs896979080	C>G,T	Pathogenic	Non coding transcript variant, missense variant, stop gained, coding sequence variant
rs1057517834	GCAG>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant, non coding transcript variant
rs1064794474	ACAG>-	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1064796606	TG>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant, non coding transcript variant
rs1064796835	AGAC>GCTGCCTTGGCT	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1266047546	->A	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant
rs1554077988	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained, genic downstream transcript variant
rs1554078461	->G	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs1554080460	->G	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs1554080589	GT>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs1554081108	AA>-	Pathogenic, likely-pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant
rs1554081112	GAAA>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant
rs1554081168	CT>-	Pathogenic	Coding sequence variant, stop gained, genic downstream transcript variant
rs1554133681	TG>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554136123	->C	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554137113	->CA	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554137419	AA>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554137531	CT>-	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1554138811	C>G	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1554138819	AG>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1561540623	->G	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs1562347303	AG>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1581064385	G>A	Likely-pathogenic	Splice donor variant
rs1581075356	CG>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1581114957	->C	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1581136492	G>-	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1581138487	AGTGAGAAAC>-	Pathogenic	Intron variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1581203344	C>T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs1581210464	A>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs1581223107	AA>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs1581224630	C>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs1581224984	->C	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs1581226008	AGCAA>-	Likely-pathogenic	Downstream transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022519	hsa-miR-124-3p	Proteomics;Microarray	18668037
MIRT025404	hsa-miR-34a-5p	Proteomics	21566225
MIRT025762	hsa-miR-7-5p	Microarray	19073608
MIRT032257	hsa-let-7b-5p	Proteomics	18668040
MIRT049104	hsa-miR-92a-3p	CLASH	23622248
MIRT048102	hsa-miR-197-3p	CLASH	23622248
MIRT046740	hsa-miR-222-3p	CLASH	23622248
MIRT043611	hsa-miR-151a-3p	CLASH	23622248
MIRT043143	hsa-miR-324-5p	CLASH	23622248
MIRT040570	hsa-miR-92b-3p	CLASH	23622248
MIRT040239	hsa-miR-615-3p	CLASH	23622248
MIRT038780	hsa-miR-93-3p	CLASH	23622248
MIRT037490	hsa-miR-744-5p	CLASH	23622248
MIRT458581	hsa-miR-6847-5p	PAR-CLIP	23592263
MIRT458580	hsa-miR-4257	PAR-CLIP	23592263
MIRT458579	hsa-miR-6786-5p	PAR-CLIP	23592263
MIRT458578	hsa-miR-4252	PAR-CLIP	23592263
MIRT458577	hsa-miR-3689d	PAR-CLIP	23592263
MIRT458576	hsa-miR-6851-5p	PAR-CLIP	23592263
MIRT458575	hsa-miR-3622b-5p	PAR-CLIP	23592263
MIRT458574	hsa-miR-4450	PAR-CLIP	23592263
MIRT458573	hsa-miR-6801-5p	PAR-CLIP	23592263
MIRT458572	hsa-miR-6880-5p	PAR-CLIP	23592263
MIRT458571	hsa-miR-7847-3p	PAR-CLIP	23592263
MIRT458570	hsa-miR-4701-5p	PAR-CLIP	23592263
MIRT458569	hsa-miR-588	PAR-CLIP	23592263
MIRT458568	hsa-miR-6857-5p	PAR-CLIP	23592263
MIRT439477	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT439477	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT458581	hsa-miR-6847-5p	PAR-CLIP	23592263
MIRT458580	hsa-miR-4257	PAR-CLIP	23592263
MIRT458579	hsa-miR-6786-5p	PAR-CLIP	23592263
MIRT458578	hsa-miR-4252	PAR-CLIP	23592263
MIRT458577	hsa-miR-3689d	PAR-CLIP	23592263
MIRT458576	hsa-miR-6851-5p	PAR-CLIP	23592263
MIRT458575	hsa-miR-3622b-5p	PAR-CLIP	23592263
MIRT458574	hsa-miR-4450	PAR-CLIP	23592263
MIRT458573	hsa-miR-6801-5p	PAR-CLIP	23592263
MIRT458572	hsa-miR-6880-5p	PAR-CLIP	23592263
MIRT458571	hsa-miR-7847-3p	PAR-CLIP	23592263
MIRT458570	hsa-miR-4701-5p	PAR-CLIP	23592263
MIRT458569	hsa-miR-588	PAR-CLIP	23592263
MIRT458568	hsa-miR-6857-5p	PAR-CLIP	23592263
MIRT1416629	hsa-miR-1273d	CLIP-seq
MIRT1416630	hsa-miR-1287	CLIP-seq
MIRT1416631	hsa-miR-132	CLIP-seq
MIRT1416632	hsa-miR-194	CLIP-seq
MIRT1416633	hsa-miR-212	CLIP-seq
MIRT1416634	hsa-miR-2467-3p	CLIP-seq
MIRT1416635	hsa-miR-3064-5p	CLIP-seq
MIRT1416636	hsa-miR-3182	CLIP-seq
MIRT1416637	hsa-miR-4659a-3p	CLIP-seq
MIRT1416638	hsa-miR-4659b-3p	CLIP-seq
MIRT1416639	hsa-miR-4687-3p	CLIP-seq
MIRT1416640	hsa-miR-4747-5p	CLIP-seq
MIRT1416641	hsa-miR-4761-5p	CLIP-seq
MIRT1416642	hsa-miR-4778-3p	CLIP-seq
MIRT1416643	hsa-miR-541	CLIP-seq
MIRT1416644	hsa-miR-548ag	CLIP-seq
MIRT1416645	hsa-miR-548ai	CLIP-seq
MIRT1416646	hsa-miR-626	CLIP-seq
MIRT1416647	hsa-miR-654-5p	CLIP-seq
MIRT1416648	hsa-miR-127-5p	CLIP-seq
MIRT1416631	hsa-miR-132	CLIP-seq
MIRT1416632	hsa-miR-194	CLIP-seq
MIRT1416633	hsa-miR-212	CLIP-seq
MIRT1416635	hsa-miR-3064-5p	CLIP-seq
MIRT1416636	hsa-miR-3182	CLIP-seq
MIRT1416649	hsa-miR-3190	CLIP-seq
MIRT1416650	hsa-miR-3202	CLIP-seq
MIRT1416651	hsa-miR-320e	CLIP-seq
MIRT1416652	hsa-miR-4428	CLIP-seq
MIRT1416653	hsa-miR-4533	CLIP-seq
MIRT1416637	hsa-miR-4659a-3p	CLIP-seq
MIRT1416638	hsa-miR-4659b-3p	CLIP-seq
MIRT1416639	hsa-miR-4687-3p	CLIP-seq
MIRT1416640	hsa-miR-4747-5p	CLIP-seq
MIRT1416642	hsa-miR-4778-3p	CLIP-seq
MIRT1416644	hsa-miR-548ag	CLIP-seq
MIRT1416645	hsa-miR-548ai	CLIP-seq
MIRT1416646	hsa-miR-626	CLIP-seq
MIRT2347421	hsa-miR-1183	CLIP-seq
MIRT2347422	hsa-miR-4300	CLIP-seq
MIRT2347423	hsa-miR-4643	CLIP-seq
MIRT2347424	hsa-miR-466	CLIP-seq
MIRT2347425	hsa-miR-4789-3p	CLIP-seq
MIRT2347426	hsa-miR-920	CLIP-seq
MIRT2395602	hsa-miR-3150b-3p	CLIP-seq
MIRT2395603	hsa-miR-4508	CLIP-seq
MIRT2395604	hsa-miR-4693-3p	CLIP-seq
MIRT2395605	hsa-miR-4768-3p	CLIP-seq
MIRT2395606	hsa-miR-4784	CLIP-seq
MIRT2395607	hsa-miR-486-3p	CLIP-seq
MIRT2395608	hsa-miR-665	CLIP-seq
MIRT2461263	hsa-miR-3662	CLIP-seq
MIRT2461264	hsa-miR-4270	CLIP-seq
MIRT2461265	hsa-miR-4441	CLIP-seq
MIRT2461266	hsa-miR-4653-3p	CLIP-seq
MIRT2461267	hsa-miR-580	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	TAS	9096354
GO:0001650	Component	Fibrillar center	IDA
GO:0003723	Function	RNA binding	HDA	22658674, 22681889
GO:0005515	Function	Protein binding	IPI	17620599, 23602568, 25064736, 26399832, 32707033, 32814053, 36411431
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005730	Component	Nucleolus	IBA
GO:0005730	Component	Nucleolus	IDA	15249688, 23203802
GO:0005730	Component	Nucleolus	IEA
GO:0005730	Component	Nucleolus	TAS	9096354
GO:0005829	Component	Cytosol	IDA
GO:0006417	Process	Regulation of translation	IMP	26399832
GO:0014029	Process	Neural crest formation	IMP	26399832
GO:0014032	Process	Neural crest cell development	IMP	26399832
GO:0030674	Function	Protein-macromolecule adaptor activity	IDA	26399832
GO:0042790	Process	Nucleolar large rRNA transcription by RNA polymerase I	IBA
GO:0046982	Function	Protein heterodimerization activity	IPI	26399832
GO:0097110	Function	Scaffold protein binding	IBA
GO:0097110	Function	Scaffold protein binding	IPI	23203802

Other IDs

• MIM: 606847
• HGNC: 11654
• e!Ensembl: ENSG00000070814

Protein

• UniProt ID: Q13428
• Protein name: Treacle protein (Treacher Collins syndrome protein)
• Protein function: Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: followi
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03546	Treacle	248 → 330	Treacher Collins syndrome protein Treacle	Family
  PF03546	Treacle	316 → 427	Treacher Collins syndrome protein Treacle	Family
  PF03546	Treacle	422 → 899	Treacher Collins syndrome protein Treacle	Family
  PF03546	Treacle	864 → 958	Treacher Collins syndrome protein Treacle	Family

• Sequence:

  MAEARKRRELLPLIYHHLLRAGYVRAAREVKEQSGQKCFLAQPVTLLDIYTHWQQTSELG
  RKRKAEEDAALQAKKTRVSDPISTSESSEEEEEAEAETAKATPRLASTNSSVLGADLPSS
  MKEKAKAETEKAGKTGNSMPHPATGKTVANLLSGKSPRKSAEPSANTTLVSETEEEGSVP
  AFGAAAKPGMVSAGQADSSSEDTSSSSDETDVEGKPSVKPAQVKASSVSTKESPARKAAP
  APGKVGDVTPQVKGGALPPAKRAKKPEEESESSEEGSESEEEAPAGTRSQVKASEKILQV
  RAASAPAKGTPGKGATPAPPGKAGAVASQTKAGKPEEDSESSSEESSDSEEETPAAKALL
  QAKASGKTSQVGAASAPAKESPRKGAAPAPPGKTGPAVAKAQAGKREEDSQSSSEESDSE
  EEAPAQAKPSGKAPQVRAASAPAKESPRKGAAPAPPRKTGPAAAQVQVGKQEEDSRSSSE
  ESDSDREALAAMNAAQVKPLGKSPQVKPASTMGMGPLGKGAGPVPPGKVGPATPSAQVGK
  WEEDSESSSEESSDSSDGEVPTAVAPAQEKSLGNILQAKPTSSPAKGPPQKAGPVAVQVK
  AEKPMDNSESSEESSDSADSEEAPAAMTAAQAKPALKIPQTKACPKKTNTTASAKVAPVR
  VGTQAPRKAGTATSPAGSSPAVAGGTQRPAEDSSSSEESDSEEEKTGLAVTVGQAKSVGK
  GLQVKAASVPVKGSLGQGTAPVLPGKTGPTVTQVKAEKQEDSESSEEESDSEEAAASPAQ
  VKTSVKKTQAKANPAAARAPSAKGTISAPGKVVTAAAQAKQRSPSKVKPPVRNPQNSTVL
  ARGPASVPSVGKAVATAAQAQTGPEEDSGSSEEESDSEEEAETLAQVKPSGKTHQIRAAL
  APAKESPRKGAAPTPPGKTGPSAAQAGKQDDSGSSSEESDSDGEAPAAVTSAQVIKPPLI
  FVDPNRSPAGPAATPAQAQAASTPRKARASESTARSSSSESEDEDVIPATQCLTPGIRTN
  VVTMPTAHPRIAPKASMAGASSSKESSRISDGKKQEGPATQVSKKNPASLPLTQAALKVL
  AQKASEAQPPVARTQPSSGVDSAVGTLPATSPQSTSVQAKGTNKLRKPKLPEVQQATKAP
  ESSDDSEDSSDSSSGSEEDGEGPQGAKSAHTLGPTPSRTETLVEETAAESSEDDVVAPSQ
  SLLSGYMTPGLTPANSQASKATPKLDSSPSVSSTLAAKDDPDGKQEAKPQQAAGMLSPKT
  GGKEAASGTTPQKSRKPKKGAGNPQASTLALQSNITQCLLGQPWPLNEAQVQASVVKVLT
  ELLEQERKKVVDTTKESSRKGWESRKRKLSGDQPAARTPRSKKKKKLGAGEGGEASVSPE
  KTSTTSKGKAKRDKASGDVKEKKGKGSLGSQGAKDEPEEELQKGMGTVEGGDQSNPKSKK
  EKKKSDKRKKDKEKKEKKKKAKKASTKDSESPSQKKKKKKKKTAEQTV

• Sequence length: 1488

Pathways

KEGG:

Ribosome biogenesis in eukaryotes

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
TCOF1-related disorder	Pathogenic; Likely pathogenic	rs2533519249, rs587776583, rs2532520874, rs1205557903, rs2532521575, rs2533510123, rs2534121996, rs2533393669, rs1581064385	RCV004729137 RCV003407273 RCV003402267 RCV003391474 RCV003983363 RCV003983384 RCV003983446 RCV003913911 RCV004723183	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Treacher Collins syndrome	Pathogenic	rs2150687333, rs2150623353, rs587776582, rs1763212034	RCV001777126 RCV001800168 RCV003319159 RCV003319224	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Treacher Collins syndrome 1	Likely pathogenic; Pathogenic	rs2150398853, rs2150704850, rs2150707502, rs2150713720, rs2150715791, rs2150736647, rs2150816107, rs1429628044, rs2151060146, rs2151105953, rs2151108281, rs2151102857, rs2150623353, rs2150732608, rs587776583, rs587777314, rs2150716827, rs2151108410, rs2150570748, rs2150398890, rs2150734334, rs2150726644, rs2150399547, rs2150695587, rs1195908562, rs2150555861, rs2150820128, rs2151101668, rs2151009927, rs1490116413, rs2150706662, rs2151099050, rs2151059839, rs2151100918, rs2151060309, rs2150816737, rs2534551107, rs2534300871, rs2533519249, rs2533085924, rs2533127084, rs2533648351, rs1183902447, rs2534305480, rs2534301072, rs2534642231, rs2533073814, rs2533419390, rs2533536617, rs2534523712, rs786205575, rs119470016, rs587776580, rs587776581, rs587776582, rs28941769, rs119470017, rs587776584, rs587776585, rs2533671671, rs2534527721, rs797046037, rs2534125699, rs2534528339, rs2534375369, rs2532820625, rs2533515258, rs2533516925, rs2533458182, rs2533700327, rs2533457151, rs2533455354, rs2534210632, rs2532677253, rs2533363651, rs886041506, rs1763212034, rs2533364391, rs2532678254, rs2534381580, rs2534215438, rs2534641075, rs2533487882, rs2532514925, rs2534537041, rs2533521583, rs2534378234, rs2533645355, rs2534526371, rs2533653403, rs2533691917, rs2533364557, rs2534522657, rs2534376553, rs1464183714, rs2534207979, rs2533129531, rs2533677472, rs2534375609, rs1057521108, rs1064794474, rs896979080, rs764314276, rs748805008, rs1554080589, rs1554081112, rs1554137531, rs1554138819, rs1554137419, rs1554081168, rs1554081108, rs1554136123, rs1554138811, rs1554078461, rs1562347303, rs1561540623, rs1581114957, rs1581136492, rs1581210464, rs1581223107, rs1581064385, rs1581203344, rs1581075356, rs1581224630, rs1767064064, rs35868965, rs1767850450, rs1768581035, rs1763331046, rs1761930554, rs1763559019, rs1764409337, rs1758946466, rs1763437825, rs1758963105, rs1769042136, rs1763415490, rs1766647259, rs1763794839, rs1764427494	RCV001378753 RCV001387452 RCV001385748 RCV001381083 RCV001383321 RCV001383031 RCV001380502 RCV001387620 RCV001389715 RCV001383032 RCV001383033 RCV001785055 RCV002544380 RCV001814673 RCV000114943 RCV000114944 RCV001945521 RCV001927382 RCV001953118 RCV001975163 RCV001949675 RCV002004648 RCV002007283 RCV002000132 RCV001970207 RCV001925483 RCV001912043 RCV002052099 RCV002246768 RCV002250989 RCV002251060 RCV002251103 RCV002260530 RCV002260531 RCV002269138 RCV002273095 RCV002283801 RCV002283857 RCV002283865 RCV002283923 RCV002283999 RCV002284049 RCV002471497 RCV002471820 RCV002474261 RCV002474265 RCV003060017 RCV003037129 RCV003037130 RCV003037131 RCV003987414 RCV000004166 RCV000004167 RCV000004168 RCV000004169 RCV000004170 RCV000004171 RCV000004172 RCV000004173 RCV000004174 RCV002796697 RCV002819375 RCV000192389 RCV002898715 RCV002871531 RCV002872494 RCV003015614 RCV003016312 RCV003037513 RCV003054079 RCV003039578 RCV003142496 RCV003153024 RCV003153036 RCV003153154 RCV003228232 RCV000821693 RCV003326683 RCV003988100 RCV003327320 RCV003405211 RCV003405212 RCV003448939 RCV003455888 RCV003530928 RCV003530929 RCV003531064 RCV003531332 RCV003529914 RCV003646283 RCV003646514 RCV003646541 RCV004554927 RCV003887827 RCV003988419 RCV003989921 RCV003991894 RCV004526430 RCV004547192 RCV004586472 RCV000809896 RCV000654875 RCV001387224 RCV000502683 RCV000500784 RCV000792512 RCV003444062 RCV000654879 RCV000553951 RCV000557664 RCV000543785 RCV000560133 RCV000703493 RCV000654878 RCV000654877 RCV000654876 RCV000697953 RCV000698090 RCV000799345 RCV000798536 RCV000809513 RCV000815237 RCV000818305 RCV000792464 RCV000856680 RCV000987620 RCV000987622 RCV001043546 RCV001037793 RCV001049095 RCV001270293 RCV001197777 RCV001219859 RCV001218624 RCV001216511 RCV001223862 RCV001208278 RCV001208485 RCV001233899 RCV001248111 RCV001253469 RCV001261246 RCV001263487 RCV001280837	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cleft lip/palate	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL ABNORMALITIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ehlers-Danlos syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MANDIBULOFACIAL DYSOSTOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Treacher Collins Syndrome, Dominant	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREACHER-COLLINS SYNDROME	—	ClinGen, Disgenet, Orphanet ClinGen, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Hypogammaglobulinemia	Common Variable Immunodeficiency	BEFREE	2136770		★☆☆☆☆ Found in Text Mining only
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	2523429		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma Of Esophagus	Esophageal Cancer	BEFREE	27600491		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	2523429		★☆☆☆☆ Found in Text Mining only
Aganglionosis, Colonic	Colonic Aganglionosis	BEFREE	23283078		★☆☆☆☆ Found in Text Mining only
Albinism	Albinism	BEFREE	30954000		★☆☆☆☆ Found in Text Mining only
Anophthalmos	Syndromic microphthalmia	BEFREE	10888597		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	30103703		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	30103703		★☆☆☆☆ Found in Text Mining only
Bilateral microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	BEFREE	12114479		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharospasm	Blepharospasm	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachycephaly	Brachycephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	BEFREE	26772999		★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	35093935	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36524514	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	2523429		★☆☆☆☆ Found in Text Mining only
Choanal Atresia	Choanal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cleft Palate	Cleft palate	Pubtator	18688869, 8037214	Associate	★☆☆☆☆ Found in Text Mining only
Cleft Soft Palate	Cleft Soft Palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Common Variable Immunodeficiency	Common Variable Immunodeficiency	BEFREE	2136770		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	BEFREE	20106873		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital cerebral hernia	Congenital Cerebral Hernia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital coloboma of iris	Congenital Coloboma Of Iris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	25790162		★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of thymus	Congenital Hypoplasia Of Thymus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus carinatum	Congenital Pectus Carinatum	BEFREE	24288143		★☆☆☆☆ Found in Text Mining only
Congenital small ears	Microtia	GENOMICS_ENGLAND_DG	9736782		★☆☆☆☆ Found in Text Mining only
Congenital small ears	Microtia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Craniofacial Abnormalities	Craniofacial abnormalities	Pubtator	12777385, 40390636	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Craniofacial dysostosis type 1	Craniofacial Dysostosis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	36656851	Associate	★☆☆☆☆ Found in Text Mining only
Dental Caries	Dental caries	Pubtator	33277566	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	27888722		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	39518953	Associate	★☆☆☆☆ Found in Text Mining only
Dysphasia	Dysphasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Enchondromatosis	Enchondromatosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	29285181		★☆☆☆☆ Found in Text Mining only
Fistula of branchial cleft	Fistula Of Branchial Cleft	HPO_DG			★☆☆☆☆ Found in Text Mining only
Franceschetti-Klein syndrome	Treacher Collins syndrome	CLINGEN_DG	20003452, 20106873, 25790162, 29230583, 30390570, 31307516, 8894686		★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glossoptosis	Glossoptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	36656851	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Conductive	Conductive hearing loss	Pubtator	8037214	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	25790162	Associate	★☆☆☆☆ Found in Text Mining only
Hirschsprung Disease	Hirschsprung Disease	BEFREE	23283078		★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin Disease	BEFREE	20106873		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	26103128		★☆☆☆☆ Found in Text Mining only
Hypopigmentation disorder	Hypopigmentation Disorder	BEFREE	30954000		★☆☆☆☆ Found in Text Mining only
Hypoplasia of the maxilla	Hypoplasia of the maxilla	HPO_DG			★☆☆☆☆ Found in Text Mining only
Idiopathic generalized epilepsy	Epilepsy	BEFREE	15101828		★☆☆☆☆ Found in Text Mining only
Infantile Spasm	Infantile Spasms	BEFREE	12177367		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	7923890		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	23695276		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	23695276, 39518953	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	25404284		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	25404284		★☆☆☆☆ Found in Text Mining only
Macrostomia	Macrostomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mandibulofacial Dysostosis	Mandibulofacial Dysostosis	BEFREE	10545604, 10888597, 10982400, 11013442, 12114479, 14598341, 15019983, 15039977, 15150774, 15214011, 15340364, 15759264, 15930015, 16102917, 16125876, 16465596, 16801042, 17431905, 17552945, 18246078, 19027870, 19572402, 20003452, 20106873, 21951868, 22295061, 22317976, 22415350, 22729243, 23401420, 23695276, 23838542, 24108658, 24603435, 24690222, 24994558, 26399832, 26772999, 26792133, 27711076, 28122066, 28921562, 29230583, 30186496, 30375284, 30849304, 30984975, 8838814, 8937767, 9096354, 9736782, 9811939		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mandibulofacial Dysostosis	Mandibulofacial dysostosis	Pubtator	10982400, 12777385, 16801042, 17431905, 19107148, 20003452, 20340163, 21951868, 22317976, 22415350, 23695276, 24603435, 25064736, 25512513, 25790162, 27526242, 28921562, 31307516, 32351010, 32537850, 32543076, 32909271, 33332773, 33719213, 34247110, 35595448, 39518953, 40240907, 40390636, 8037214, 8488840, 8681136, 9042910, 9074926, 9096354	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mandibulofacial Dysostosis	Mandibulofacial Dysostosis	CLINVAR_DG	11013442, 12114482, 20003452, 21951868, 22317976, 8894686, 9042910		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mandibulofacial Dysostosis	Mandibulofacial Dysostosis	GENOMICS_ENGLAND_DG	14598341, 8741923, 9736782		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mandibulofacial Dysostosis	Mandibulofacial Dysostosis	LHGDN	15039977, 15832313, 16102917		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mandibulofacial Dysostosis	Mandibulofacial Dysostosis	CTD_human_DG	16938878		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mandibulofacial Dysostosis	Mandibulofacial Dysostosis	UNIPROT_DG	9042910		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Depression	Mental Depression	BEFREE	27888722		★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microstomia	Microstomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myoclonic Epilepsy	Myoclonic Epilepsy	BEFREE	12177367		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	25404284, 27600491		★☆☆☆☆ Found in Text Mining only
Noonan Syndrome	Noonan syndrome	Pubtator	28921562	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Orofacial Cleft 1	Orofacial cleft	Pubtator	18688869	Associate	★☆☆☆☆ Found in Text Mining only
Osteochondrodysplasias	Osteochondrodysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	20692500, 30579060		★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral T-Cell Lymphoma	T-Cell Lymphoma	BEFREE	1991851		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	1826223, 1826936		★☆☆☆☆ Found in Text Mining only
Progressive supranuclear palsy	Progressive Supranuclear Palsy	BEFREE	31621617		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	BEFREE	12114479		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skeletal dysplasia	Skeletal Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Hypoplasia	Thyroid Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Treacher-Collins syndrome	Treacher Collins syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	19027870		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	39523372	Associate	★☆☆☆☆ Found in Text Mining only
Tuberous Sclerosis	Tuberous Sclerosis	BEFREE	20924998		★☆☆☆☆ Found in Text Mining only
Uranostaphyloschisis	Uranostaphyloschisis	BEFREE	18688869		★☆☆☆☆ Found in Text Mining only
West Syndrome	West Syndrome	BEFREE	12177367		★☆☆☆☆ Found in Text Mining only