CYP11B1 (cytochrome P450 family 11 subfamily B member 1)

Gene

• Entrez ID: 1584
• Gene name: Cytochrome P450 family 11 subfamily B member 1
• Gene symbol: CYP11B1
• Synonyms (NCBI Gene): CPN1, CYP11B, FHI, P450C11
• Chromosome: 8
• Chromosome location: 8q24.3
• Summary: This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein local

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28934586	C>T	Likely-pathogenic, pathogenic	Intron variant, coding sequence variant, missense variant
rs61751149	G>A,C,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, missense variant
rs61752766	T>C	Benign, uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs61752786	G>A,C,T	Benign, likely-pathogenic, likely-benign, benign-likely-benign	Coding sequence variant, synonymous variant, missense variant
rs104894061	G>A,C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs104894062	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs104894066	C>T	Pathogenic	Coding sequence variant, stop gained
rs104894067	T>C,G	Pathogenic	Coding sequence variant, missense variant
rs104894068	G>A	Pathogenic	Coding sequence variant, missense variant
rs104894069	G>A	Not-provided, pathogenic	Coding sequence variant, missense variant
rs104894070	G>A,T	Not-provided, pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs104894071	G>T	Pathogenic	Coding sequence variant, missense variant
rs140336749	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs146124466	G>A	Pathogenic	Coding sequence variant, stop gained
rs193922538	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs193922539	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs193922540	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs193922541	A>G	Likely-pathogenic	Splice donor variant
rs267606755	A>C	Pathogenic-likely-pathogenic	Stop gained, intron variant, coding sequence variant
rs367634557	C>T	Likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs387907572	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs387907573	A>G,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs577022490	A>G,T	Likely-pathogenic	Splice donor variant, intron variant
rs748867146	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs753774484	C>A,G,T	Likely-pathogenic	Coding sequence variant, synonymous variant
rs760880418	G>A,T	Likely-pathogenic	Synonymous variant, coding sequence variant, stop gained
rs763195324	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant, stop gained
rs764418169	CCAGGCTCATCCTGTGGGGATGCAGGCT>-	Pathogenic	Frameshift variant, coding sequence variant
rs764598023	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs768007725	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs775128501	->GTGTACTGTTG	Pathogenic, likely-pathogenic	Frameshift variant, coding sequence variant
rs779103938	C>T	Pathogenic-likely-pathogenic, likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs866430018	C>T	Pathogenic	Stop gained, coding sequence variant
rs1131691992	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1249087390	G>-	Pathogenic	Frameshift variant, intron variant, coding sequence variant
rs1256580853	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1264073726	C>T	Pathogenic, likely-pathogenic	Splice donor variant
rs1326688256	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs1365173817	C>A,T	Pathogenic	Intron variant
rs1379392398	->T	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1383321200	C>G,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1456715954	C>T	Likely-pathogenic	Splice acceptor variant
rs1554652650	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant, intron variant
rs1554652990	C>G	Likely-pathogenic	Splice donor variant
rs1554652998	C>T	Pathogenic	Coding sequence variant, stop gained
rs1554652999	C>T	Pathogenic	Coding sequence variant, stop gained
rs1554653514	C>G	Likely-pathogenic	Splice donor variant
rs1554653520	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554653551	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1554653675	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1554653714	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1563867899	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant
rs1586557065	T>C	Pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT920376	hsa-miR-1915	CLIP-seq
MIRT920377	hsa-miR-2115	CLIP-seq
MIRT920378	hsa-miR-2355-5p	CLIP-seq
MIRT920379	hsa-miR-3177-3p	CLIP-seq
MIRT920380	hsa-miR-3183	CLIP-seq
MIRT920381	hsa-miR-3649	CLIP-seq
MIRT920382	hsa-miR-4287	CLIP-seq
MIRT920383	hsa-miR-4469	CLIP-seq
MIRT920384	hsa-miR-4685-3p	CLIP-seq
MIRT920385	hsa-miR-4723-3p	CLIP-seq
MIRT920386	hsa-miR-516a-3p	CLIP-seq
MIRT920387	hsa-miR-1225-5p	CLIP-seq
MIRT920388	hsa-miR-1226	CLIP-seq
MIRT920389	hsa-miR-1253	CLIP-seq
MIRT920390	hsa-miR-1299	CLIP-seq
MIRT920391	hsa-miR-1304	CLIP-seq
MIRT920392	hsa-miR-185	CLIP-seq
MIRT920393	hsa-miR-2682	CLIP-seq
MIRT920394	hsa-miR-299-3p	CLIP-seq
MIRT920395	hsa-miR-3074-5p	CLIP-seq
MIRT920396	hsa-miR-3124-3p	CLIP-seq
MIRT920397	hsa-miR-3184	CLIP-seq
MIRT920398	hsa-miR-3672	CLIP-seq
MIRT920399	hsa-miR-371-5p	CLIP-seq
MIRT920400	hsa-miR-371b-5p	CLIP-seq
MIRT920401	hsa-miR-3918	CLIP-seq
MIRT920402	hsa-miR-423-5p	CLIP-seq
MIRT920403	hsa-miR-4271	CLIP-seq
MIRT920404	hsa-miR-4279	CLIP-seq
MIRT920405	hsa-miR-4306	CLIP-seq
MIRT920406	hsa-miR-4475	CLIP-seq
MIRT920407	hsa-miR-4476	CLIP-seq
MIRT920408	hsa-miR-449c	CLIP-seq
MIRT920409	hsa-miR-4505	CLIP-seq
MIRT920410	hsa-miR-4639-3p	CLIP-seq
MIRT920411	hsa-miR-4644	CLIP-seq
MIRT920412	hsa-miR-4648	CLIP-seq
MIRT920413	hsa-miR-4654	CLIP-seq
MIRT920414	hsa-miR-4659a-3p	CLIP-seq
MIRT920415	hsa-miR-4659b-3p	CLIP-seq
MIRT920416	hsa-miR-4682	CLIP-seq
MIRT920417	hsa-miR-4725-3p	CLIP-seq
MIRT920418	hsa-miR-4733-3p	CLIP-seq
MIRT920419	hsa-miR-4769-5p	CLIP-seq
MIRT920420	hsa-miR-4778-3p	CLIP-seq
MIRT920421	hsa-miR-4782-5p	CLIP-seq
MIRT920422	hsa-miR-516b	CLIP-seq
MIRT920423	hsa-miR-548a-3p	CLIP-seq
MIRT920424	hsa-miR-548e	CLIP-seq
MIRT920425	hsa-miR-548f	CLIP-seq
MIRT920426	hsa-miR-625	CLIP-seq
MIRT920427	hsa-miR-940	CLIP-seq
MIRT1972754	hsa-miR-1197	CLIP-seq
MIRT1972755	hsa-miR-1224-5p	CLIP-seq
MIRT1972756	hsa-miR-1294	CLIP-seq
MIRT920390	hsa-miR-1299	CLIP-seq
MIRT1972757	hsa-miR-1321	CLIP-seq
MIRT1972758	hsa-miR-3120-3p	CLIP-seq
MIRT1972759	hsa-miR-3136-3p	CLIP-seq
MIRT1972760	hsa-miR-328	CLIP-seq
MIRT1972761	hsa-miR-3607-5p	CLIP-seq
MIRT1972762	hsa-miR-4269	CLIP-seq
MIRT1972763	hsa-miR-4316	CLIP-seq
MIRT1972764	hsa-miR-4514	CLIP-seq
MIRT1972765	hsa-miR-451b	CLIP-seq
MIRT920416	hsa-miR-4682	CLIP-seq
MIRT1972766	hsa-miR-4692	CLIP-seq
MIRT1972767	hsa-miR-4739	CLIP-seq
MIRT1972768	hsa-miR-4742-5p	CLIP-seq
MIRT1972769	hsa-miR-4751	CLIP-seq
MIRT1972770	hsa-miR-4756-5p	CLIP-seq
MIRT920421	hsa-miR-4782-5p	CLIP-seq
MIRT920422	hsa-miR-516b	CLIP-seq
MIRT1972771	hsa-miR-615-5p	CLIP-seq
MIRT1972772	hsa-miR-661	CLIP-seq
MIRT1972773	hsa-miR-875-3p	CLIP-seq
MIRT1972754	hsa-miR-1197	CLIP-seq
MIRT1972755	hsa-miR-1224-5p	CLIP-seq
MIRT1972756	hsa-miR-1294	CLIP-seq
MIRT1972758	hsa-miR-3120-3p	CLIP-seq
MIRT1972761	hsa-miR-3607-5p	CLIP-seq
MIRT2208427	hsa-miR-3692	CLIP-seq
MIRT1972763	hsa-miR-4316	CLIP-seq
MIRT1972765	hsa-miR-451b	CLIP-seq
MIRT1972769	hsa-miR-4751	CLIP-seq
MIRT2208428	hsa-miR-622	CLIP-seq
MIRT2208429	hsa-miR-938	CLIP-seq
MIRT2386633	hsa-miR-28-5p	CLIP-seq
MIRT2386634	hsa-miR-3139	CLIP-seq
MIRT2386635	hsa-miR-4283	CLIP-seq
MIRT2386636	hsa-miR-4489	CLIP-seq
MIRT2386637	hsa-miR-4492	CLIP-seq
MIRT2386638	hsa-miR-4498	CLIP-seq
MIRT2386639	hsa-miR-708	CLIP-seq
MIRT2386640	hsa-miR-762	CLIP-seq
MIRT2512288	hsa-miR-1254	CLIP-seq
MIRT2512289	hsa-miR-151-5p	CLIP-seq
MIRT2512290	hsa-miR-151b	CLIP-seq
MIRT2512291	hsa-miR-3116	CLIP-seq
MIRT2512292	hsa-miR-4254	CLIP-seq
MIRT2512288	hsa-miR-1254	CLIP-seq
MIRT2512289	hsa-miR-151-5p	CLIP-seq
MIRT2512290	hsa-miR-151b	CLIP-seq
MIRT2512291	hsa-miR-3116	CLIP-seq
MIRT2512292	hsa-miR-4254	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ATF1	Unknown	11014212;11196473
ATF2	Unknown	11014212;11196473
CREB1	Unknown	11196473
NR5A1	Unknown	11014212
NR5A2	Activation	11564608

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004497	Function	Monooxygenase activity	IEA
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IBA
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IDA	2256920, 8506298, 18215163
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IEA
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	IMP	2022736
GO:0004507	Function	Steroid 11-beta-monooxygenase activity	TAS
GO:0005506	Function	Iron ion binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	2256920
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IBA
GO:0005743	Component	Mitochondrial inner membrane	IC	8506298
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	ISS
GO:0005743	Component	Mitochondrial inner membrane	TAS	15026188
GO:0006066	Process	Alcohol metabolic process	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006694	Process	Steroid biosynthetic process	IEA
GO:0006700	Process	C21-steroid hormone biosynthetic process	IDA	2256920
GO:0006700	Process	C21-steroid hormone biosynthetic process	IEA
GO:0006704	Process	Glucocorticoid biosynthetic process	IBA
GO:0006704	Process	Glucocorticoid biosynthetic process	IEA
GO:0006704	Process	Glucocorticoid biosynthetic process	TAS
GO:0006955	Process	Immune response	TAS	12452430
GO:0008203	Process	Cholesterol metabolic process	IBA
GO:0008217	Process	Regulation of blood pressure	IMP	2022736
GO:0016020	Component	Membrane	IEA
GO:0016125	Process	Sterol metabolic process	IEA
GO:0016125	Process	Sterol metabolic process	TAS
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016705	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	IEA
GO:0020037	Function	Heme binding	IC	2256920
GO:0020037	Function	Heme binding	IEA
GO:0032342	Process	Aldosterone biosynthetic process	IBA
GO:0032342	Process	Aldosterone biosynthetic process	IDA	2256920
GO:0032342	Process	Aldosterone biosynthetic process	IMP	19342457
GO:0032870	Process	Cellular response to hormone stimulus	IEP	19342457
GO:0034650	Process	Cortisol metabolic process	IBA
GO:0034651	Process	Cortisol biosynthetic process	IDA	8506298, 18215163
GO:0034651	Process	Cortisol biosynthetic process	IMP	2022736, 19342457
GO:0035865	Process	Cellular response to potassium ion	IEP	19342457
GO:0042593	Process	Glucose homeostasis	TAS	16114325
GO:0046872	Function	Metal ion binding	IEA
GO:0047783	Function	Corticosterone 18-monooxygenase activity	IBA
GO:0071375	Process	Cellular response to peptide hormone stimulus	IBA

Other IDs

• MIM: 610613
• HGNC: 2591
• e!Ensembl: ENSG00000160882

Protein

• UniProt ID: P15538
• Protein name: Cytochrome P450 11B1, mitochondrial (CYP11B1) (CYPXIB1) (Cytochrome P-450c11) (Cytochrome P450C11) (Steroid 11-beta-hydroxylase, CYP11B1) (EC 1.14.15.4)
• Protein function: A cytochrome P450 monooxygenase involved in the biosynthesis of adrenal corticoids (PubMed:12530636, PubMed:1518866, PubMed:1775135, PubMed:18215163, PubMed:23322723). Catalyzes a variety of reactions that are essential for many species, includi
• PDB: 6M7X, 7E7F
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00067	p450	42 → 498	Cytochrome P450	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the zona fasciculata/reticularis of the adrenal cortex. {ECO:0000269|PubMed:20200334}.
• Sequence:

  MALRAKAEVCMAVPWLSLQRAQALGTRAARVPRTVLPFEAMPRRPGNRWLRLLQIWREQG
  YEDLHLEVHQTFQELGPIFRYDLGGAGMVCVMLPEDVEKLQQVDSLHPHRMSLEPWVAYR
  QHRGHKCGVFLLNGPEWRFNRLRLNPEVLSPNAVQRFLPMVDAVARDFSQALKKKVLQNA
  RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
  PRSLSRWTSPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFSRPQQYTSIVAELLLNAELS
  PDAIKANSMELTAGSVDTTVFPLLMTLFELARNPNVQQALRQESLAAAASISEHPQKATT
  ELPLLRAALKETLRLYPVGLFLERVASSDLVLQNYHIPAGTLVRVFLYSLGRNPALFPRP
  ERYNPQRWLDIRGSGRNFYHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHLQVETLTQED
  IKMVYSFILRPSMFPLLTFRAIN

• Sequence length: 503

Pathways

KEGG:

Steroid hormone biosynthesis
Metabolic pathways
Cortisol synthesis and secretion
Cushing syndrome

Reactome:

Glucocorticoid biosynthesis
Endogenous sterols
Defective CYP11B1 causes Adrenal hyperplasia 4 (AH4)

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
Congenital adrenal hyperplasia	Pathogenic; Likely pathogenic	rs780398462, rs1327055239, rs775479837, rs772003869, rs753774484, rs104894062, rs104894069, rs1365173817, rs104894070, rs2130266157, rs775946442, rs1307064483, rs1264073726, rs2488676492, rs193922538, rs193922539, rs193922541, rs1412048304, rs367634557, rs1489638195, rs1563867837, rs387907572, rs1447069098	RCV003331773 RCV001806163 RCV001779162 RCV004770317 RCV005432875 RCV005887159 RCV000029642 RCV004585979 RCV000029646 RCV002240087 RCV002282830 RCV003155793 RCV003230921 RCV004586335 RCV003387864 RCV000029643 RCV000029645 RCV000029648 RCV004702305 RCV004526748 RCV002271551 RCV003387915 RCV005406793 RCV002282447	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
CYP11B1-related disorder	Likely pathogenic; Pathogenic	rs28934586, rs267606755, rs1256580853, rs753774484, rs760880418, rs368944209, rs1554652528, rs375833424	RCV004751188 RCV003415613 RCV003403212 RCV004751577 RCV004751658 RCV003420186 RCV003420179 RCV004751955	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Deficiency of steroid 11-beta-monooxygenase	Pathogenic; Likely pathogenic	rs28934586, rs1327055239, rs1369163428, rs775479837, rs375892072, rs1437397442, rs2130267209, rs2130274854, rs769310764, rs142484434, rs775946442, rs758714890, rs2130273520, rs1221010438, rs104894061, rs104894062, rs104894066, rs104894067, rs104894068, rs104894069, rs1586557065, rs1365173817, rs267606755, rs104894070, rs104894071, rs2130266157, rs1421641874, rs2130273191, rs2130266809, rs2130266841, rs2488678124, rs2488677593, rs1360208732, rs2488678145, rs2488678032, rs2488678074, rs2488678148, rs2130277148, rs2488677362, rs2488677344, rs2488678202, rs141305721, rs777626314, rs1816968040, rs779103938, rs1307064483, rs370404312, rs2488675946, rs759939173, rs1816966972, rs2488674652, rs761488596, rs777844820, rs2488676544, rs778735553, rs2488677327, rs2488681079, rs2488681073, rs2488681030, rs267601810, rs2488678051, rs2488677617, rs750428278, rs2488676743, rs2488675856, rs2488681916, rs2488676492, rs1256580853, rs753774484, rs775128501, rs193922538, rs760880418, rs368944209, rs1326688256, rs1554652999, rs1554653514, rs764418169, rs763195324, rs1554652650, rs1412048304, rs1554653185, rs764251434, rs1554652528, rs1554653520, rs748867146, rs577022490, rs1554653714, rs367634557, rs764598023, rs1456715954, rs1554652990, rs1554652998, rs866430018, rs1379392398, rs1554653551, rs1489638195, rs1554653675, rs1383321200, rs1563867837, rs146124466, rs140336749, rs387907573, rs387907572, rs149881706, rs1447069098, rs1816901292, rs1816980417, rs1214983921, rs1816949224, rs5290, rs1479660166, rs1816889095, rs375833424, rs1816868757	RCV001332501 RCV002476727 RCV003463035 RCV003469726 RCV001535982 RCV001667863 RCV001667864 RCV003471042 RCV003471159 RCV003470993 RCV003464351 RCV002279773 RCV003471199 RCV003471195 RCV000001230 RCV000001232 RCV000001233 RCV000001235 RCV000001236 RCV000001237 RCV000001238 RCV000001240 RCV000001242 RCV000001244 RCV000001245 RCV000001246 RCV002496178 RCV005042757 RCV002251185 RCV002251187 RCV002269805 RCV002306490 RCV002309563 RCV002310011 RCV002308096 RCV002309163 RCV002309422 RCV002309467 RCV002306897 RCV002306928 RCV002307082 RCV002307203 RCV005045183 RCV005045352 RCV005045169 RCV000672120 RCV005636852 RCV003388670 RCV003468616 RCV003468617 RCV003468618 RCV003468619 RCV003468620 RCV003468622 RCV003468623 RCV003468624 RCV003468625 RCV003468626 RCV003459895 RCV003459896 RCV003459898 RCV003459899 RCV003459902 RCV003459906 RCV004575746 RCV004575747 RCV004575748 RCV005040709 RCV000668755 RCV000667365 RCV000668927 RCV002482915 RCV000671118 RCV000670290 RCV000667891 RCV000674543 RCV000673849 RCV000667039 RCV000667072 RCV000666356 RCV000673616 RCV000673116 RCV000668003 RCV000667414 RCV000667181 RCV000674573 RCV000674749 RCV000674379 RCV000672406 RCV000667465 RCV000666001 RCV000673530 RCV000670838 RCV000669979 RCV000667792 RCV000672570 RCV000670507 RCV000665385 RCV000674113 RCV000672260 RCV004569402 RCV000050222 RCV000050223 RCV000050224 RCV000050225 RCV000050227 RCV002497451 RCV003469377 RCV005040042 RCV005049788 RCV001264085 RCV001264086 RCV001264087 RCV002250741 RCV001290136 RCV001290137	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Differences in sex development	Likely pathogenic; Pathogenic	rs1489638195	RCV005865375	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Glucocorticoid-remediable aldosteronism	Pathogenic; Likely pathogenic	rs28934586, rs1327055239, rs375892072, rs758714890, rs104894061, rs104894068, rs104894069, rs1586557065, rs1365173817, rs267606755, rs104894070, rs2130266157, rs1421641874, rs141305721, rs777626314, rs1816968040, rs779103938, rs1816900835, rs2488676492, rs1256580853, rs193922538, rs760880418, rs1326688256, rs1554652999, rs764418169, rs763195324, rs1412048304, rs367634557, rs764598023, rs146124466, rs140336749, rs387907573, rs149881706, rs1447069098, rs1816980417, rs1214983921, rs375833424	RCV003989685 RCV002476727 RCV001535982 RCV005042487 RCV001199200 RCV002504733 RCV002247232 RCV002476907 RCV002496225 RCV005049306 RCV005041962 RCV002490289 RCV002496178 RCV002249852 RCV005045183 RCV005045352 RCV005045169 RCV002494612 RCV003984889 RCV005040709 RCV002481670 RCV002482915 RCV005046891 RCV005046876 RCV005049653 RCV005046866 RCV005049638 RCV005046906 RCV005046898 RCV000763177 RCV000763178 RCV005042164 RCV005042165 RCV005042166 RCV002497451 RCV005040042 RCV005049788 RCV005040131	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ADRENAL HYPERPLASIA DUE TO 11-BETA-HYDROXYLASE DEFICIENCY	—	CTD, Disgenet, GenCC, Orphanet CTD, Disgenet, GenCC, Orphanet CTD, Disgenet, GenCC, Orphanet CTD, Disgenet, GenCC, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CUSHING SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL HYPERALDOSTERONISM TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL HYPERALDOSTERONISM TYPE I	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERALDOSTERONISM	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERALDOSTERONISM, FAMILIAL, TYPE I	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
11-Beta-hydroxylase deficiency	11-beta-hydroxylase deficiency	BEFREE	1430088, 15324322, 15549155, 17726333, 18663314, 19567537, 20024693, 20089618, 2022736, 20331679, 20947076, 22210247, 22921894, 22964742, 23146819, 23345044, 24022297, 24536089, 25911436, 25913739, 26066897, 26476331, 26806323, 26956189, 27316665, 27928728, 28126912, 28514642, 29626607, 29703198, 29909741, 30223866, 30241518, 30242600, 7488170, 7889175, 7903314, 7988480, 8506298, 8530633, 9302260, 9329393, 9435454		★☆☆☆☆ Found in Text Mining only
11-Beta-hydroxylase deficiency	11-beta-hydroxylase deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	12457455, 20708777, 21848792, 28405879, 28422753, 29069700, 31351131, 7588406, 8008746		★☆☆☆☆ Found in Text Mining only
Adrenal Cortical Adenoma	Adrenocortical adenoma	BEFREE	27754862		★☆☆☆☆ Found in Text Mining only
Adrenal cortical hypofunction	Adrenal Cortical Hypofunction	BEFREE	23345044		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Neoplasms	Adrenal neoplasia	BEFREE	1775135		★☆☆☆☆ Found in Text Mining only
Adrenal hyperplasia	Adrenal hyperplasia	BEFREE	9302260		★☆☆☆☆ Found in Text Mining only
Adrenal hyperplasia	Adrenal hyperplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adrenal Hyperplasia Congenital	Congenital adrenal hyperplasia	Pubtator	24022297, 24621779, 27316665, 27376426, 28126912, 28228528, 30241518, 33708317, 34616364, 34823514, 36927563, 37486441, 38027139, 39402525, 39952853, 8506298	Associate	★☆☆☆☆ Found in Text Mining only
Adrenocortical carcinoma	Adrenocortical carcinoma	BEFREE	29734384		★☆☆☆☆ Found in Text Mining only
Adrenocortical Carcinoma	Adrenocortical carcinoma	Pubtator	34918636	Associate	★☆☆☆☆ Found in Text Mining only
Adrenogenital Syndrome	Adrenogenital Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	BEFREE	31332713		★☆☆☆☆ Found in Text Mining only
Ambiguous Genitalia	Ambiguous Genitalia	BEFREE	10487675		★☆☆☆☆ Found in Text Mining only
Ambiguous genitalia, female	Ambiguous Genitalia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aplasia Cutis Congenita	Aplasia Cutis Congenita	BEFREE	31332713		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	26690694		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	26690694		★☆☆☆☆ Found in Text Mining only
Bartter Disease	Bartter syndrome	BEFREE	23345044		★☆☆☆☆ Found in Text Mining only
Bilateral Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	30425102		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	30478747, 30769265		★☆☆☆☆ Found in Text Mining only
CCHS WITH HIRSCHSPRUNG DISEASE	Haddad syndrome	BEFREE	7903314		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic sinusitis	Sinusitis	BEFREE	24810847		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	BEFREE	10559665, 11196457, 11443188, 12428205, 1430088, 14682466, 15755848, 15807871, 16024935, 16030166, 16670167, 17124386, 18663314, 19029289, 19844114, 19931309, 20089618, 2022736, 20523022, 22210247, 22921894, 23345044, 23940125, 24621779, 25100385, 25911436, 26053152, 26066897, 26806323, 28126912, 29703198, 30241518, 8506298, 8952579, 9302260, 9435454		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	LHGDN	15699546, 15755848, 18294861, 18661760		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency	Congenital adrenal hyperplasia	CLINVAR_DG	10487675, 15751602, 15755848, 15807871, 16046588, 16670167, 17371482, 17726333, 18663314, 20089618, 2022736, 22964742, 23940125, 24022297, 24334966, 24536089, 24987415, 25911436, 26053152, 26066897, 26265915, 26280318, 26476331, 26956189, 28228528, 8506298, 8768848, 8964882, 9302260, 9435454		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency	Congenital adrenal hyperplasia	GENOMICS_ENGLAND_DG	11549691		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency	Congenital adrenal hyperplasia	BEFREE	1430088, 15324322, 15549155, 17726333, 18663314, 19567537, 20024693, 20089618, 2022736, 20331679, 20947076, 22210247, 22921894, 22964742, 23146819, 23345044, 24022297, 24536089, 25911436, 25913739, 26066897, 26476331, 26806323, 26956189, 27316665, 27928728, 28126912, 28514642, 29626607, 29703198, 29909741, 30223866, 30241518, 30242600, 7488170, 7889175, 7903314, 7988480, 8506298, 8530633, 8768848, 9302260, 9329393, 9435454		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency	Congenital adrenal hyperplasia	UNIPROT_DG	16046588, 20089618, 2022736, 20331679, 20947076, 23940125, 24022297, 24536089, 24987415, 26053152, 26476331, 9302260		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency	Congenital adrenal hyperplasia	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency	Congenital adrenal hyperplasia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency	Congenital adrenal hyperplasia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency	Congenital adrenal hyperplasia	BEFREE	24022297		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency	Congenital adrenal hyperplasia	Pubtator	24022297, 27376426	Associate	★☆☆☆☆ Found in Text Mining only
Congenital central hypoventilation syndrome	Congenital central hypoventilation syndrome	Pubtator	20947076, 24022297, 27316665, 30241518, 35685215, 38027139, 39402525	Associate	★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of adrenal gland	Congenital adrenal hypoplasia	BEFREE	16439455		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	11914098, 15134825		★☆☆☆☆ Found in Text Mining only
Conn Adenoma	Conn Adenoma	BEFREE	16715648, 23012392, 27751767, 27754862, 29436482, 7792812		★☆☆☆☆ Found in Text Mining only
Conn Syndrome	Conn Syndrome	BEFREE	10843166, 15579186, 22083159, 23443813, 24943299, 25555247		★☆☆☆☆ Found in Text Mining only
Conn Syndrome	Conn Syndrome	CTD_human_DG	11085685		★☆☆☆☆ Found in Text Mining only
Coronary Disease	Coronary artery disease	Pubtator	35831903	Associate	★☆☆☆☆ Found in Text Mining only
Corticosterone Methyl Oxidase Type I Deficiency	Corticosterone Methyl Oxidase Deficiency	BEFREE	7792802		★☆☆☆☆ Found in Text Mining only
Corticosterone Methyl Oxidase Type II Deficiency	Corticosterone Methyl Oxidase Deficiency	BEFREE	7792802		★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	BEFREE	24810847		★☆☆☆☆ Found in Text Mining only
Cushing Syndrome	Cushing`s Syndrome	BEFREE	12608705, 19564722, 21848792, 27454103, 29312923, 30572739, 30769265		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	33245660	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	35831903	Associate	★☆☆☆☆ Found in Text Mining only
Disorder of Sex Development 46 XY	46, xy disorder of sex development	Pubtator	39285472	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ectodermal Dysplasia	Ectodermal dysplasia	Pubtator	26772981	Associate	★☆☆☆☆ Found in Text Mining only
Ectopic adrenal gland	Ectopic adrenal gland	HPO_DG			★☆☆☆☆ Found in Text Mining only
Enlarged polycystic ovaries	Enlarged polycystic ovaries	HPO_DG			★☆☆☆☆ Found in Text Mining only
Essential Hypertension	Hypertension	BEFREE	23150505		★☆☆☆☆ Found in Text Mining only
Familial hyperaldosteronism type I	Hyperaldosteronism	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	BEFREE	16670167, 9329393		★☆☆☆☆ Found in Text Mining only
Female sexual dysfunction	Female sexual dysfunction	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glucocorticoid-remediable aldosteronism	Hyperaldosteronism	BEFREE	10843166, 11600544, 1303253, 1472060, 15062555, 1518866, 16110193, 1731223, 20808686, 21625068, 26066897, 31287546, 8070423, 9814482		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glucocorticoid-remediable aldosteronism	Hyperaldosteronism	GENOMICS_ENGLAND_DG	11549691		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glucocorticoid-remediable aldosteronism	Hyperaldosteronism	ORPHANET_DG	20634641, 24817817		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glucocorticoid-remediable aldosteronism	Hyperaldosteronism	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glucocorticoid-remediable aldosteronism	Hyperaldosteronism	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Gynecomastia	Gynecomastia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperaldosteronism	Hyperaldosteronism	BEFREE	10323392, 24943299		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperaldosteronism	Hyperaldosteronism	CTD_human_DG	11085685		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperaldosteronism	Hyperaldosteronism	LHGDN	11903322		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperaldosteronism	Hyperaldosteronism	Pubtator	1518866, 20808686, 24837548, 24866132, 25958045, 27681703, 27754862, 28405879, 31484828, 33796077, 35012455, 7593610	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperaldosteronism	Hyperaldosteronism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypernatriuria	Hypernatriuria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	30241518, 32854392, 33708317, 35831903, 8506298	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	11095433, 11196457, 11964027, 15134825, 17121536, 18663314, 20708777, 22921894, 23150505, 23345044, 28116713, 28272372, 29703198, 30242600, 30478747, 7593610, 8506298, 9719043		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertrophy of clitoris	Hypertrophy Of Clitoris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypokalemic alkalosis	Hypokalemia	BEFREE	23345044		★☆☆☆☆ Found in Text Mining only
Hypoplasia of vagina	Hypoplasia Of Vagina	HPO_DG			★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	29909741	Associate	★☆☆☆☆ Found in Text Mining only
Larsen syndrome dominant type	Larsen syndrome	Pubtator	39402525	Associate	★☆☆☆☆ Found in Text Mining only
Liddle Syndrome	Liddle Syndrome	BEFREE	11128865		★☆☆☆☆ Found in Text Mining only
Lipoid congenital adrenal hyperplasia	Congenital lipoid adrenal hyperplasia	Pubtator	34823514	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30425102		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of kidney	Kidney Cancer	BEFREE	12457455		★☆☆☆☆ Found in Text Mining only
Metabolic alkalosis	Metabolic alkalosis	BEFREE	30661045		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	29312923		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome	Metabolic syndrome	Pubtator	33708317	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	11422106, 1775135, 19564722, 23443813, 28405879		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	26976855, 33708317	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pervasive Development Disorder	Autism spectrum disorder	BEFREE	26690694		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	27376426	Associate	★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	3058471		★☆☆☆☆ Found in Text Mining only
Precocious Puberty	Precocious puberty	BEFREE	11964027		★☆☆☆☆ Found in Text Mining only
Premature adrenarche	Premature adrenarche	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal carcinoma	Renal Carcinoma	BEFREE	12457455		★☆☆☆☆ Found in Text Mining only
Secretory adrenocortical adenoma	Secretory adrenocortical adenoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	7473536		★☆☆☆☆ Found in Text Mining only
Trifunctional Protein Deficiency With Myopathy And Neuropathy	Trifunctional protein deficiency	Pubtator	39952853	Associate	★☆☆☆☆ Found in Text Mining only
X-linked Adrenal Hypoplasia	Adrenal Hypoplasia, X-Linked	BEFREE	16439455		★☆☆☆☆ Found in Text Mining only