CGNL1

Summary

CGNL1 (cingulin like 1, HGNC:25931) is a protein-coding gene on chromosome 15q21.3, encoding Cingulin-like protein 1 (Q0VF96). May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons.

This gene encodes a member of the cingulin family. The encoded protein localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1. Heterozygous chromosomal rearrangements resulting in association of the promoter for this gene with the aromatase gene are a cause of aromatase excess syndrome. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 84952 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 297 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_032866

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25931
Approved symbol	CGNL1
Name	cingulin like 1
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14957, JACOP, KIAA1749, PCING
Ensembl gene	ENSG00000128849
Ensembl biotype	protein_coding
OMIM	607856
Entrez	84952

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000281282, ENST00000557813, ENST00000559194, ENST00000860576, ENST00000860577, ENST00000860578, ENST00000860579, ENST00000860580, ENST00000860581, ENST00000860582, ENST00000860583, ENST00000926796, ENST00000926797, ENST00000955754, ENST00000955755, ENST00000955756, ENST00000955757, ENST00000955758, ENST00000955759

RefSeq mRNA: 2 — MANE Select: NM_032866 NM_001252335, NM_032866

CCDS: CCDS10161

Canonical transcript exons

ENST00000281282 — 19 exons

Exon	Start	End
ENSE00000884903	57546076	57546239
ENSE00000931462	57524581	57524751
ENSE00000931463	57528654	57528815
ENSE00000931465	57543696	57543779
ENSE00000941924	57453683	57453818
ENSE00001000491	57516780	57516986
ENSE00001000492	57461680	57461892
ENSE00001103542	57437985	57439601
ENSE00001103545	57547355	57550717
ENSE00001103547	57442373	57442478
ENSE00001103555	57440377	57440471
ENSE00001103557	57451500	57451601
ENSE00001103574	57452141	57452289
ENSE00001183207	57376505	57376567
ENSE00001221220	57545592	57545700
ENSE00001221228	57544473	57544597
ENSE00001221244	57531690	57531779
ENSE00001221269	57523489	57523641
ENSE00001221348	57518393	57518497

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3268 / max 176.3244, expressed in 926 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146845	5.2183	834
146843	0.5985	339
146844	0.3408	192
146847	0.1692	111

Top tissues by expression

258 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.59	gold quality
parotid gland	UBERON:0001831	98.61	gold quality
renal medulla	UBERON:0000362	97.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.47	gold quality
upper arm skin	UBERON:0004263	97.15	gold quality
adult mammalian kidney	UBERON:0000082	95.53	gold quality
kidney	UBERON:0002113	94.41	gold quality
adult organism	UBERON:0007023	94.00	gold quality
urethra	UBERON:0000057	93.41	gold quality
left ventricle myocardium	UBERON:0006566	92.74	gold quality
metanephros cortex	UBERON:0010533	92.64	gold quality
skin of hip	UBERON:0001554	92.07	gold quality
liver	UBERON:0002107	91.90	gold quality
upper leg skin	UBERON:0004262	91.55	gold quality
vena cava	UBERON:0004087	91.30	gold quality
seminal vesicle	UBERON:0000998	90.41	gold quality
visceral pleura	UBERON:0002401	90.40	gold quality
metanephros	UBERON:0000081	89.99	gold quality
synovial joint	UBERON:0002217	89.91	gold quality
lower lobe of lung	UBERON:0008949	89.61	gold quality
right lobe of liver	UBERON:0001114	89.40	gold quality
placenta	UBERON:0001987	89.08	gold quality
myocardium	UBERON:0002349	89.03	gold quality
cortex of kidney	UBERON:0001225	89.00	gold quality
prostate gland	UBERON:0002367	89.00	gold quality
oral cavity	UBERON:0000167	87.95	gold quality
germinal epithelium of ovary	UBERON:0001304	87.90	gold quality
uterine cervix	UBERON:0000002	87.67	gold quality
amniotic fluid	UBERON:0000173	87.52	gold quality
parietal pleura	UBERON:0002400	87.33	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	64.18
E-ANND-3	yes	18.84
E-HCAD-35	yes	18.32
E-CURD-11	no	159.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting CGNL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 6)

• This paper studied the mouse JACOP protein and found that the JACOP protein has structural and functional similarities to cingulin. (PMID:15292197)
• Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions (PMID:18653465)
• ZO-1 and PLEKHA7 are paracingulin-interacting proteins that are involved in its recruitment to epithelial tight and adherens junctions, respectively (PMID:21454477)
• Results indentify plausible candidates include non-recurrent deletions at the glutamate transporter gene SLC1A1, a CNV locus recently suggested to be involved in schizophrenia through linkage analysis, and duplications at 1p36.33 and CGNL1. (PMID:24163246)
• MgcRacGAP colocalizes with CGN and CGNL1 at TJs and forms a complex and interacts directly in vitro with CGN and CGNL1. (PMID:24807907)
• demonstrate in a postnatal retinal vascular development model in mice that Cgnl1 function is crucial for sustaining neovascular growth and stability (PMID:29016873)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cgnl1	ENSDARG00000015805
mus_musculus	Cgnl1	ENSMUSG00000032232
rattus_norvegicus	Cgnl1	ENSRNOG00000054080

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Cingulin-like protein 1 — Q0VF96 (reviewed: Q0VF96)

Alternative names: Junction-associated coiled-coil protein, Paracingulin

All UniProt accessions (1): Q0VF96

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons.

Subunit / interactions. Homodimer or oligomer. Interacts with CD2AP and SH3BP1; probably part of a complex at cell junctions.

Subcellular location. Cell junction. Tight junction.

Tissue specificity. Smooth muscle, spleen, testis, fetal brain, amygdala, corpus callosum, cerebellum, thalamus and subthalamic nucleus of adult brain.

Disease relevance. Aromatase excess syndrome (AEXS) [MIM:139300] An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration inv(15)(q21.2;q21.3) has been found in patients with aromatase excess syndrome. The inversion moves the promoter of the CGNL1 gene into a 5-prime position in relation to the aromatase coding region.

Domain organisation. The head region is responsible for both junction and actin filament-based distribution.

Similarity. Belongs to the cingulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q0VF96-1	1	yes
Q0VF96-2	2

RefSeq proteins (2): NP_001239264, NP_116255* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002928	Myosin_tail	Domain

Pfam: PF01576

UniProt features (47 total): sequence conflict 13, region of interest 9, modified residue 9, compositionally biased region 7, sequence variant 5, chain 1, coiled-coil region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0VF96-F1	64.25	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 112, 202, 283, 297, 298, 388, 391, 486, 708

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, ROZANOV_MMP14_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION

GO Biological Process (4): actin filament organization (GO:0007015), negative regulation of small GTPase mediated signal transduction (GO:0051058), negative regulation of stress fiber assembly (GO:0051497), protein localization to cell-cell junction (GO:0150105)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): bicellular tight junction (GO:0005923), myosin complex (GO:0016459), protein-containing complex (GO:0032991), actin cytoskeleton (GO:0015629), apical junction complex (GO:0043296), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton organization	1
supramolecular fiber organization	1
small GTPase-mediated signal transduction	1
regulation of small GTPase mediated signal transduction	1
negative regulation of intracellular signal transduction	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
protein localization to cell junction	1
binding	1
apical junction complex	1
tight junction	1
actin cytoskeleton	1
protein-containing complex	1
cellular_component	1
cytoskeleton	1
cell-cell junction	1
cell junction	1

Protein interactions and networks

STRING

1501 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CGNL1	ARHGEF2	Q92974	924
CGNL1	TMOD3	Q9NYL9	906
CGNL1	A0A087WZG4	A0A087WZG4	872
CGNL1	ARHGEF18	Q6ZSZ5	872
CGNL1	RACGAP1	Q9H0H5	839
CGNL1	PLEKHA7	Q6IQ23	826
CGNL1	CYP19A1	P11511	774
CGNL1	TMOD2	Q9NZR1	760
CGNL1	OCLN	Q16625	740
CGNL1	CAMSAP3	Q9P1Y5	662
CGNL1	TJP1	Q07157	647
CGNL1	MARVELD2	Q8N4S9	626
CGNL1	TIAM1	Q13009	603
CGNL1	ARHGEF11	O15085	554
CGNL1	TRPM7	Q96QT4	549

IntAct

44 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
LURAP1	TRIM24	psi-mi:“MI:0914”(association)	0.530
CGNL1	RCN2	psi-mi:“MI:0915”(physical association)	0.400
CGNL1	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
PDIA5	CGNL1	psi-mi:“MI:0915”(physical association)	0.400
CGNL1	EEF1G	psi-mi:“MI:0915”(physical association)	0.400
CGNL1		psi-mi:“MI:0915”(physical association)	0.370
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
BCAR1	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
BCAR1	CEP290	psi-mi:“MI:0914”(association)	0.350
CGNL1	HMMR	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SLC30A3	WWP2	psi-mi:“MI:0914”(association)	0.350
SLC35G3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SLC39A13	SCO1	psi-mi:“MI:0914”(association)	0.350
HOOK2	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (72): TRAF7 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), HMMR (Affinity Capture-MS), GRIPAP1 (Affinity Capture-MS), CGNL1 (Affinity Capture-RNA), CGNL1 (Proximity Label-MS), CGNL1 (Proximity Label-MS), CGNL1 (Proximity Label-MS), CGNL1 (Proximity Label-MS), RCN2 (Proximity Label-MS), PDIA5 (Proximity Label-MS), CGNL1 (Proximity Label-MS), CGNL1 (Proximity Label-MS), CGNL1 (Affinity Capture-RNA), CGNL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GUX5, A0A1L8GXY6, A0A1W2P884, A2CE83, B8A5S6, E7F5E1, F7DP49, H2MTR9, O08970, O35711, O60296, P27628, P53564, P60853, Q0VF96, Q28GJ0, Q2KJD6, Q3UIJ9, Q4V7D3, Q5BIX7, Q5R923, Q5SXA9, Q5SZL2, Q5U2Y9, Q5U4W1, Q5ZLT3, Q6AW69, Q6DIS8, Q6DJR2, Q6NRW2, Q6NXJ0, Q6P402, Q6PCQ0, Q6PD31, Q7TQE6, Q80ST9, Q86W92, Q8BMK0, Q8C8U0, Q8CFC9

Diamond homologs: A7YH32, A9X1A5, B0KWC9, B1MTG4, B1WB65, B3EX63, P14105, P59242, Q0VF96, Q1L8T5, Q6AW69, Q99105, Q9P2M7, Q9PTD7, P35579, Q258K2, P10587, P35580, P35749, A2AQP0, A7E2Y1, F1PT61, G3UW82, O96064, P02562, P02563, P02564, P02565, P02566, P02567, P04462, P05661, P06198, P10567, P11055, P11778, P12844, P12845, P12847, P12882

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	177.6×	3e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	156.8×	5e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	156.8×	5e-13
Activation of BH3-only proteins	7	115.9×	5e-12
RHO GTPases activate PKNs	7	74.0×	1e-10
Intrinsic Pathway for Apoptosis	7	68.3×	2e-10
FOXO-mediated transcription	5	56.0×	3e-07
Apoptosis	8	44.8×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	53.9×	4e-06
substantia nigra development	5	53.9×	4e-06
intracellular protein localization	7	21.6×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

297 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	238
Likely benign	28
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1340208	GRCh37/hg19 15q21.3(chr15:55772371-57880518)x1	Pathogenic
2427772	NC_000015.9:g.(?56961021)(57839688_?)del	Pathogenic
100883	NM_032866.5(CGNL1):c.2322T>C (p.His774=)	Likely pathogenic

SpliceAI

4476 predictions. Top by Δscore:

Variant	Effect	Δscore
15:57437979:T:TA	acceptor_gain	1.0000
15:57440438:C:G	donor_gain	1.0000
15:57440467:GAAGG:G	donor_gain	1.0000
15:57440470:GG:G	donor_gain	1.0000
15:57440471:GG:G	donor_gain	1.0000
15:57442468:G:GT	donor_gain	1.0000
15:57442469:A:T	donor_gain	1.0000
15:57442479:G:GG	donor_gain	1.0000
15:57442486:G:GT	donor_gain	1.0000
15:57442486:G:T	donor_gain	1.0000
15:57451492:A:AG	acceptor_gain	1.0000
15:57451493:A:G	acceptor_gain	1.0000
15:57451497:TAGGC:T	acceptor_loss	1.0000
15:57451498:A:AG	acceptor_gain	1.0000
15:57451498:AG:A	acceptor_gain	1.0000
15:57451498:AGGCT:A	acceptor_loss	1.0000
15:57451499:G:GA	acceptor_gain	1.0000
15:57451499:G:GT	acceptor_loss	1.0000
15:57451499:GG:G	acceptor_gain	1.0000
15:57451499:GGC:G	acceptor_gain	1.0000
15:57451499:GGCT:G	acceptor_gain	1.0000
15:57451499:GGCTT:G	acceptor_gain	1.0000
15:57451593:G:GT	donor_gain	1.0000
15:57451597:TCA:T	donor_gain	1.0000
15:57451599:AAG:A	donor_gain	1.0000
15:57451600:AGGT:A	donor_loss	1.0000
15:57451602:G:C	donor_loss	1.0000
15:57451602:G:GG	donor_gain	1.0000
15:57452135:TGTTA:T	acceptor_loss	1.0000
15:57452136:GTTA:G	acceptor_loss	1.0000

AlphaMissense

8608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:57546118:G:C	A1218P	1.000
15:57440462:T:C	L563P	0.999
15:57453736:T:C	L703P	0.999
15:57453748:T:C	L707P	0.999
15:57461768:T:C	L760P	0.999
15:57546077:T:C	L1204P	0.999
15:57546104:G:C	R1213P	0.999
15:57438166:T:A	V56D	0.998
15:57440450:T:A	L559H	0.998
15:57440450:T:C	L559P	0.998
15:57442417:T:A	V581D	0.998
15:57442429:T:C	I585T	0.998
15:57442438:T:C	L588S	0.998
15:57453769:T:C	L714P	0.998
15:57545633:G:C	R1181P	0.998
15:57545648:T:C	L1186P	0.998
15:57546086:G:C	R1207P	0.998
15:57546140:T:C	L1225P	0.998
15:57438130:T:A	I44N	0.997
15:57438130:T:C	I44T	0.997
15:57439008:T:C	F337L	0.997
15:57439010:C:A	F337L	0.997
15:57439010:C:G	F337L	0.997
15:57439066:T:C	L356S	0.997
15:57439077:T:C	F360L	0.997
15:57439079:T:A	F360L	0.997
15:57439079:T:G	F360L	0.997
15:57440442:G:C	K556N	0.997
15:57440442:G:T	K556N	0.997
15:57440462:T:A	L563H	0.997

dbSNP variants (sampled 300 via entrez): RS1000007593 (15:57435287 G>A,C,T), RS1000011608 (15:57402074 G>T), RS1000036848 (15:57435079 G>A), RS1000053863 (15:57517940 G>A,T), RS1000054283 (15:57471113 A>G), RS1000071012 (15:57465728 C>T), RS1000107671 (15:57407532 G>C,T), RS1000177376 (15:57525633 C>T), RS1000192889 (15:57547134 T>A), RS1000235596 (15:57415053 A>G), RS1000236254 (15:57486175 A>C), RS1000257883 (15:57451525 A>G), RS1000267021 (15:57486378 G>A,C), RS1000280765 (15:57520108 T>A), RS1000289409 (15:57510488 G>T)

Disease associations

OMIM: gene MIM:607856 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000969_1	Bipolar disorder (age of onset and psychotic symptoms)	1.000000e-06
GCST004297_9	Atrial fibrillation	3.000000e-08
GCST006976_93	Macular thickness	7.000000e-09
GCST007022_3	Type 2 diabetes nephropathy including microalbuminuria	2.000000e-07
GCST007673_16	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST007876_121	Estimated glomerular filtration rate	3.000000e-08
GCST008058_285	Estimated glomerular filtration rate	1.000000e-11
GCST008059_178	Estimated glomerular filtration rate	5.000000e-13
GCST012319_1	LDL levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	9.000000e-09
GCST90002383_269	Hematocrit	3.000000e-11
GCST90002384_380	Hemoglobin	9.000000e-11
GCST90002403_482	Red blood cell count	2.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0009603	stroke outcome severity measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	9
Benzo(a)pyrene	affects methylation, decreases expression	6
Aflatoxin B1	affects expression, decreases expression, decreases methylation	5
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	increases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1

Clinical trials (associated diseases)

75 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists