CENPI

Summary

CENPI (centromere protein I, HGNC:3968) is a protein-coding gene on chromosome Xq22.1, encoding Centromere protein I (Q92674). Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. It is a selective cancer dependency (DepMap: 64.3% of cell lines).

This gene encodes a centromere protein that is a component of the CENPA-NAC (nucleosome-associated) complex. This complex is critical for accurate chromosome alignment and segregation and it ensures proper mitotic progression. This protein regulates the recruitment of kinetochore-associated proteins that are required to generate the spindle checkpoint signal. The product of this gene is involved in the response of gonadal tissues to follicle-stimulating hormone. Mutations in this gene may be involved in human X-linked disorders of gonadal development and gametogenesis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 13.

Source: NCBI Gene 2491 — RefSeq curated summary.

At a glance

• Gene–disease (curated): idiopathic steroid-sensitive nephrotic syndrome (Limited, GenCC)
• Clinical variants (ClinVar): 167 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 64.3% of screened cell lines
• MANE Select transcript: NM_001386188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3968
Approved symbol	CENPI
Name	centromere protein I
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	LRPR1, CENP-I, Mis6
Ensembl gene	ENSG00000102384
Ensembl biotype	protein_coding
OMIM	300065
Entrez	2491

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000372926, ENST00000372927, ENST00000403304, ENST00000423383, ENST00000435570, ENST00000682095, ENST00000682304, ENST00000684367, ENST00000907101, ENST00000907102, ENST00000933782, ENST00000933783, ENST00000933784

RefSeq mRNA: 4 — MANE Select: NM_001386188 NM_001318521, NM_001318523, NM_001386188, NM_006733

CCDS: CCDS14479, CCDS83482, CCDS94639

Canonical transcript exons

ENST00000682095 — 22 exons

Exon	Start	End
ENSE00000673914	101161528	101161569
ENSE00001550567	101098444	101098539
ENSE00001597237	101109891	101109998
ENSE00001615691	101129982	101130073
ENSE00001619633	101101058	101101296
ENSE00001625012	101120402	101120450
ENSE00001626919	101128716	101128836
ENSE00001639390	101145064	101145199
ENSE00001666684	101120738	101120784
ENSE00001689878	101132392	101132456
ENSE00001691668	101147763	101147811
ENSE00001692344	101127138	101127266
ENSE00001717959	101147943	101148161
ENSE00001721477	101132190	101132307
ENSE00001732891	101127498	101127665
ENSE00001739846	101109473	101109591
ENSE00001766972	101102274	101102411
ENSE00001769955	101146153	101146277
ENSE00001783483	101126709	101126798
ENSE00002148330	101140666	101140760
ENSE00003916201	101098204	101098248
ENSE00003919764	101162833	101166126

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 90.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1802 / max 169.1686, expressed in 1411 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196941	8.1802	1411

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	90.01	gold quality
oocyte	CL:0000023	85.81	gold quality
ventricular zone	UBERON:0003053	84.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.45	gold quality
ganglionic eminence	UBERON:0004023	81.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.10	gold quality
embryo	UBERON:0000922	76.60	gold quality
stromal cell of endometrium	CL:0002255	76.53	gold quality
adrenal tissue	UBERON:0018303	73.93	gold quality
diaphragm	UBERON:0001103	73.75	gold quality
frontal pole	UBERON:0002795	71.98	gold quality
endometrium epithelium	UBERON:0004811	71.82	silver quality
paraflocculus	UBERON:0005351	71.65	gold quality
middle frontal gyrus	UBERON:0002702	71.34	gold quality
buccal mucosa cell	CL:0002336	71.04	gold quality
smooth muscle tissue	UBERON:0001135	70.55	gold quality
bone marrow	UBERON:0002371	70.27	gold quality
rectum	UBERON:0001052	69.91	gold quality
olfactory bulb	UBERON:0002264	69.72	gold quality
type B pancreatic cell	CL:0000169	69.56	gold quality
trabecular bone tissue	UBERON:0002483	68.15	gold quality
epithelial cell of pancreas	CL:0000083	67.75	gold quality
vermiform appendix	UBERON:0001154	67.39	gold quality
lymph node	UBERON:0000029	66.16	gold quality
mucosa of transverse colon	UBERON:0004991	65.92	gold quality
esophagus mucosa	UBERON:0002469	65.63	gold quality
caecum	UBERON:0001153	65.53	gold quality
tongue squamous epithelium	UBERON:0006919	65.52	gold quality
bone marrow cell	CL:0002092	65.46	silver quality
pancreatic ductal cell	CL:0002079	65.20	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting CENPI, 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-8485	100.00	77.57	4731
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6734-3P	99.15	66.27	1627

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• The CENP-H-I complex may function, in part, as a marker directing CENP-A deposition to centromeres. (PMID:16622420)
• the vertebrate KNL1 counterpart is essential for chromosome segregation and is required to localize a subset of outer kinetochore proteins. (PMID:18045986)
• demonstrates that CENPI, a centromere protein that localizes to the inner kinetochore structure, is a human autoantigen. The significance of anti-CENPI autoantibodies could be relevant in scleroderma patients as a marker for autoimmune liver disease (PMID:21888900)
• We conclude that the dual activities of Aurora B and CENP-I generate a molecular switch that maintains a robust spindle checkpoint signal at prometaphase kinetochores until they attain mature attachments to microtubules. (PMID:24862574)
• mutation in LRPAP1 is associated with high myopia. Further studies are expected to evaluate the pathogenicity of the variants in CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2. (PMID:25525168)
• CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. (PMID:26527398)
• CENPI is overexpressed in colorectal cancer (CRC) and functions as oncogene in modulating CRC cell migration, invasion and epithelial-mesenchymal transition process. (PMID:29936263)
• Centromere protein I (CENPI) is a candidate gene for X-linked steroid sensitive nephrotic syndrome. (PMID:31912435)
• Centromere Protein I (CENP-I) Is Upregulated in Gastric Cancer, Predicts Poor Prognosis, and Promotes Tumor Cell Proliferation and Migration. (PMID:34617858)
• Immune infiltration related CENPI associates with the malignant features and drug resistance of lung adenocarcinoma. (PMID:38232915)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cenpi	ENSDARG00000052565
mus_musculus	Cenpi	ENSMUSG00000031262
rattus_norvegicus	Cenpi	ENSRNOG00000033335

Protein

Protein identifiers

Centromere protein I — Q92674 (reviewed: Q92674)

Alternative names: FSH primary response protein 1, Follicle-stimulating hormone primary response protein, Interphase centromere complex protein 19, Leucine-rich primary response protein 1

All UniProt accessions (5): Q92674, A0A804HK71, A0A8C8KX99, Q5JX01, Q5JX02

UniProt curated annotations — full annotation on UniProt →

Function. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Required for the localization of CENPF, MAD1L1 and MAD2 (MAD2L1 or MAD2L2) to kinetochores. Involved in the response of gonadal tissues to follicle-stimulating hormone.

Subunit / interactions. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Interacts with SENP6.

Subcellular location. Nucleus. Chromosome. Centromere.

Post-translational modifications. Sumoylated. Sumoylated form can be polyubiquitinated by RNF4, leading to its degradation. Desumoylation by SENP6 prevents its degradation.

Induction. By follicle-stimulating hormone (FSH).

Similarity. Belongs to the CENP-I/CTF3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92674-1	1	yes
Q92674-2	2

RefSeq proteins (4): NP_001305450, NP_001305452, NP_001373117, NP_006724 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012485	CENP-I	Family

Pfam: PF07778

UniProt features (64 total): helix 37, sequence conflict 8, strand 8, turn 6, compositionally biased region 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7PB4	X-RAY DIFFRACTION	2.49
28OP	ELECTRON MICROSCOPY	2.7
7R5S	ELECTRON MICROSCOPY	2.83
7PKN	ELECTRON MICROSCOPY	3.2
7XHO	ELECTRON MICROSCOPY	3.29
9TAW	ELECTRON MICROSCOPY	3.54
7XHN	ELECTRON MICROSCOPY	3.71
7R5V	ELECTRON MICROSCOPY	4.55
7QOO	ELECTRON MICROSCOPY	4.6
7YYH	ELECTRON MICROSCOPY	8.9
7YWX	ELECTRON MICROSCOPY	12
9TAY	ELECTRON MICROSCOPY	15.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92674-F1	74.27	0.23

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73886	Chromosome Maintenance
R-HSA-774815	Nucleosome assembly
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 172 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, PUJANA_CHEK2_PCC_NETWORK, GCM_RING1, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_ORGANELLE_FISSION, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_ORGANELLE_ASSEMBLY, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GARY_CD5_TARGETS_DN, GOBP_MITOTIC_CELL_CYCLE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_SEX_DIFFERENTIATION, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (5): mitotic sister chromatid segregation (GO:0000070), chromosome segregation (GO:0007059), sex differentiation (GO:0007548), CENP-A containing chromatin assembly (GO:0034080), obsolete centromere complex assembly (GO:0034508)

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

GO Cellular Component (8): kinetochore (GO:0000776), inner kinetochore (GO:0000939), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear body (GO:0016604), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cell Cycle	3
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Nucleosome assembly	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Chromosome Maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
cellular anatomical structure	2
sister chromatid segregation	1
mitotic nuclear division	1
mitotic cell cycle process	1
cell cycle process	1
developmental process involved in reproduction	1
chromatin organization	1
kinetochore assembly	1
protein localization to CENP-A containing chromatin	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleoplasm	1
chromosomal region	1

Protein interactions and networks

STRING

3932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPI	CENPH	Q9H3R5	999
CENPI	CENPK	Q9BS16	999
CENPI	CENPM	Q9NSP4	995
CENPI	CENPU	Q71F23	993
CENPI	CENPA	P49450	988
CENPI	CENPO	Q9BU64	988
CENPI	CENPN	Q96H22	984
CENPI	CENPL	Q8N0S6	979
CENPI	CENPP	Q6IPU0	977
CENPI	CENPC	Q03188	966
CENPI	CENPQ	Q7L2Z9	963
CENPI	CENPT	Q96BT3	952
CENPI	CENPX	A8MT69	916
CENPI	ITGB3BP	Q13352	910
CENPI	CENPB	P07199	885

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CENPH	NDC80	psi-mi:“MI:0914”(association)	0.800
ITGB3BP	CENPU	psi-mi:“MI:0914”(association)	0.710
CENPK	CENPI	psi-mi:“MI:0915”(physical association)	0.670
CEP76	CENPI	psi-mi:“MI:0915”(physical association)	0.560
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
ZNF71	NVL	psi-mi:“MI:0914”(association)	0.530
CENPH	ITGB3BP	psi-mi:“MI:0914”(association)	0.530
CENPK	DHRS12	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
CENPI	NPM1	psi-mi:“MI:0915”(physical association)	0.400
Cenph	CENPX	psi-mi:“MI:0914”(association)	0.350
CENPO	CENPX	psi-mi:“MI:0914”(association)	0.350
CENPQ	CENPX	psi-mi:“MI:0914”(association)	0.350
ITGB3BP	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
CENPU	CENPX	psi-mi:“MI:0914”(association)	0.350
DGCR8	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
NIFK	RRP8	psi-mi:“MI:0914”(association)	0.350
CENPU	PLK1	psi-mi:“MI:0914”(association)	0.350
CENPM	CENPI	psi-mi:“MI:0914”(association)	0.350
SRP14	RPSA2	psi-mi:“MI:0914”(association)	0.350
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350
RPL36	GTPBP10	psi-mi:“MI:0914”(association)	0.350
RPL13		psi-mi:“MI:0914”(association)	0.350
ZNF346	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
RPLP0	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Affinity Capture-MS), CENPI (Proximity Label-MS), CENPI (Affinity Capture-RNA), CENPI (Two-hybrid), CENPI (Proximity Label-MS)

ESM2 similar proteins: A2RRP1, A4D1B5, E1BGH8, O43149, O88480, P53995, Q12769, Q13129, Q13315, Q3MHH2, Q3TCV3, Q3TUL7, Q3UHA3, Q3UPC7, Q3URV1, Q402B2, Q4R7B1, Q4R9E9, Q5H9S7, Q5RB52, Q5SSH7, Q5ZL79, Q5ZLS8, Q62388, Q63517, Q6P2C0, Q6TNU3, Q86VV8, Q8BJW5, Q8CE72, Q8IV33, Q8K1K4, Q8K2A7, Q8NB91, Q8NG48, Q8R4Y8, Q8TEL6, Q91VB4, Q920I9, Q92674

Diamond homologs: Q63517, Q8AYS7, Q8K1K4, Q92674

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CENPI	“form complex”	“CCAN complex”	binding

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
Nucleosome assembly	8	131.3×	1e-13
Chromosome Maintenance	8	58.3×	5e-11
Amplification of signal from the kinetochores	8	54.3×	6e-11
Deposition of new CENPA-containing nucleosomes at the centromere	9	49.2×	1e-11
Mitotic Spindle Checkpoint	8	43.8×	2e-10
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	9	36.2×	7e-11
EML4 and NUDC in mitotic spindle formation	9	28.8×	4e-10
Cell Cycle Checkpoints	9	27.5×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
chromosome segregation	10	47.0×	2e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	57
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
493606	GRCh37/hg19 Xq22.1(chrX:99742359-100759773)x3	Likely pathogenic

SpliceAI

3036 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101101292:GAAAG:G	donor_gain	1.0000
X:101101294:AAGG:A	donor_loss	1.0000
X:101101295:AGG:A	donor_loss	1.0000
X:101101296:GG:G	donor_loss	1.0000
X:101102270:TCA:T	acceptor_loss	1.0000
X:101102271:CA:C	acceptor_loss	1.0000
X:101102272:A:AG	acceptor_gain	1.0000
X:101102272:AGGTC:A	acceptor_loss	1.0000
X:101102273:G:GT	acceptor_gain	1.0000
X:101102273:GGT:G	acceptor_gain	1.0000
X:101102273:GGTCC:G	acceptor_gain	1.0000
X:101102412:G:GG	donor_gain	1.0000
X:101109885:CAATA:C	acceptor_loss	1.0000
X:101109887:ATAGG:A	acceptor_loss	1.0000
X:101109888:TAGG:T	acceptor_loss	1.0000
X:101109889:A:C	acceptor_loss	1.0000
X:101109890:G:GT	acceptor_loss	1.0000
X:101109995:ACTG:A	donor_gain	1.0000
X:101109995:ACTGG:A	donor_loss	1.0000
X:101109996:CTG:C	donor_gain	1.0000
X:101109996:CTGG:C	donor_loss	1.0000
X:101109997:TG:T	donor_gain	1.0000
X:101109997:TGGT:T	donor_loss	1.0000
X:101109998:GG:G	donor_gain	1.0000
X:101109999:G:GA	donor_loss	1.0000
X:101109999:G:GG	donor_gain	1.0000
X:101110000:T:TC	donor_loss	1.0000
X:101120736:A:AG	acceptor_gain	1.0000
X:101120737:G:GG	acceptor_gain	1.0000
X:101127136:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000095347 (X:101171489 G>T), RS1000113753 (X:101103254 A>G,T), RS1000123874 (X:101169092 A>G), RS1000143218 (X:101147881 T>G), RS1000146326 (X:101171739 T>C), RS1000264894 (X:101148500 C>T), RS1000309564 (X:101153282 T>A), RS1000331022 (X:101113175 T>C), RS1000338832 (X:101153692 A>G), RS1000625854 (X:101155246 G>A), RS1000656827 (X:101155481 C>T), RS1000666535 (X:101110680 T>G), RS1000722850 (X:101171778 A>G), RS1000789097 (X:101174397 G>A), RS1000889541 (X:101147182 A>G)

Disease associations

OMIM: gene MIM:300065 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
idiopathic steroid-sensitive nephrotic syndrome	Limited	X-linked

Mondo (2): premature menopause (MONDO:0001119), idiopathic steroid-sensitive nephrotic syndrome (MONDO:0019067)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
chromium hexavalent ion	increases abundance, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Folic Acid	affects cotreatment, decreases expression	2
Methotrexate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	decreases expression	1
N(4)-hydroxycytidine	increases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
phenethyl isothiocyanate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
incobotulinumtoxinA	decreases expression	1

Clinical trials (associated diseases)

82 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