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): 171 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 12 tissues, sQTL in 2 (q < 0.05)
• Cancer dependency (DepMap): dependent in 64.3% of screened cell lines
• MANE Select transcript: NM_001386188
• Interaction hub: 2,227 STRING partners (top 6% of genes corpus-wide)
• Notable: 171 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 16 — 16 protein_coding

MANE Select: ENST00000682095

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 3: 2, TSL 5: 3

ENST00000682095, ENST00000372926, ENST00000372927, ENST00000403304, ENST00000423383, ENST00000435570, ENST00000682304, ENST00000684367, ENST00000907101, ENST00000907102, ENST00000933782, ENST00000933783, ENST00000933784, ENST00001115760, ENST00001115761, ENST00001134351

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
ENSE00004784490	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.

Highest expression (Bgee): secondary oocyte, oocyte, ventricular zone, primordial germ cell in gonad, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CENPI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	sqtl	1.6e-13	+0.58	X:101099897:C:G
Cells Cultured fibroblasts	sqtl	5.6e-10	+0.40	X:101099897:C:G
Artery Tibial	eqtl	9.5e-04	+0.15	X:101138253:T:G
Esophagus Gastroesophageal Junction	eqtl	7.0e-03	+0.45	X:100123944:C:G
Skin Sun Exposed Lower leg	eqtl	7.3e-03	-0.07	X:100957536:T:C
Artery Aorta	eqtl	7.8e-03	+0.18	X:101182403:T:G
Bladder	eqtl	8.9e-03	+3.66	X:101158569:G:A
Nerve Tibial	eqtl	1.5e-02	+0.18	X:100867715:G:A
Cells Cultured fibroblasts	eqtl	1.9e-02	-0.05	X:101280831:A:C
Colon Sigmoid	eqtl	2.1e-02	+0.21	X:101152794:C:CTA
Esophagus Muscularis	eqtl	2.4e-02	+0.13	X:101202245:G:A
Vagina	eqtl	3.2e-02	+1.00	X:100445342:G:C
Stomach	eqtl	4.5e-02	-0.49	X:101616795:G:A
Brain Frontal Cortex BA9	eqtl	4.5e-02	-0.77	X:100737851:CCATT:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
196941	8.1802	1411

Top tissues by expression

showing 100 of 280 tissues 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
endothelial cell	CL:0000115	64.35	gold quality
endometrium	UBERON:0001295	63.84	gold quality
duodenum	UBERON:0002114	63.52	gold quality
thymus	UBERON:0002370	63.48	gold quality
colonic epithelium	UBERON:0000397	62.85	silver quality
placenta	UBERON:0001987	62.70	gold quality
amniotic fluid	UBERON:0000173	62.50	silver quality
islet of Langerhans	UBERON:0000006	62.41	gold quality
tonsil	UBERON:0002372	62.31	gold quality
gingival epithelium	UBERON:0001949	62.30	gold quality
tendon of biceps brachii	UBERON:0008188	62.26	gold quality
cartilage tissue	UBERON:0002418	62.17	silver quality
cortical plate	UBERON:0005343	62.12	gold quality
oral cavity	UBERON:0000167	61.98	silver quality
orbitofrontal cortex	UBERON:0004167	61.90	gold quality
left ovary	UBERON:0002119	61.78	gold quality
ovary	UBERON:0000992	61.49	gold quality
esophagus	UBERON:0001043	61.34	gold quality
right ovary	UBERON:0002118	61.34	gold quality
ectocervix	UBERON:0012249	61.26	gold quality
popliteal artery	UBERON:0002250	61.20	gold quality
tibial artery	UBERON:0007610	61.15	gold quality
transverse colon	UBERON:0001157	61.07	gold quality
cerebellar vermis	UBERON:0004720	60.95	gold quality
uterus	UBERON:0000995	60.56	gold quality
colon	UBERON:0001155	60.47	gold quality
large intestine	UBERON:0000059	60.40	gold quality
intestine	UBERON:0000160	60.38	gold quality
jejunal mucosa	UBERON:0000399	60.36	silver quality
calcaneal tendon	UBERON:0003701	60.29	gold quality
gingiva	UBERON:0001828	60.22	gold quality
female reproductive system	UBERON:0000474	60.19	gold quality
body of uterus	UBERON:0009853	60.08	gold quality
tibial nerve	UBERON:0001323	60.01	gold quality
squamous epithelium	UBERON:0006914	59.95	silver quality
epithelium of nasopharynx	UBERON:0001951	59.93	gold quality
tibia	UBERON:0000979	59.87	gold quality
aorta	UBERON:0000947	59.85	gold quality
tendon	UBERON:0000043	59.75	gold quality
esophagus squamous epithelium	UBERON:0006920	59.54	silver quality
Brodmann (1909) area 10	UBERON:0013541	59.54	gold quality
descending thoracic aorta	UBERON:0002345	59.47	gold quality
small intestine	UBERON:0002108	58.97	gold quality
sigmoid colon	UBERON:0001159	58.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.65	gold quality
colonic mucosa	UBERON:0000317	58.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	58.60	silver quality
vagina	UBERON:0000996	58.58	gold quality
epithelium of esophagus	UBERON:0001976	58.57	silver quality
small intestine Peyer’s patch	UBERON:0003454	58.44	gold quality
spleen	UBERON:0002106	58.35	gold quality
decidua	UBERON:0002450	58.28	gold quality
thoracic aorta	UBERON:0001515	58.26	gold quality
ascending aorta	UBERON:0001496	58.17	gold quality
left coronary artery	UBERON:0001626	58.11	gold quality
subcutaneous adipose tissue	UBERON:0002190	57.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	57.08	gold quality
lower esophagus mucosa	UBERON:0035834	56.97	gold quality
coronary artery	UBERON:0001621	56.93	gold quality
uterine cervix	UBERON:0000002	56.92	gold quality
myometrium	UBERON:0001296	56.88	gold quality
stomach	UBERON:0000945	56.66	gold quality
right adrenal gland	UBERON:0001233	56.42	gold quality
connective tissue	UBERON:0002384	56.36	gold quality
gall bladder	UBERON:0002110	56.27	gold quality
lower lobe of lung	UBERON:0008949	56.17	silver quality
omental fat pad	UBERON:0010414	56.12	gold quality
lower esophagus	UBERON:0013473	56.10	gold quality
peritoneum	UBERON:0002358	56.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	56.05	gold 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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	11.1
Nucleus accumbens	tissue	10.7
Hippocampus	tissue	10.6
Locus coeruleus	tissue	9.4
Postcentral gyrus	tissue	8.9
Corpus callosum	tissue	7.1
Bone marrow	tissue	5.2
Putamen	tissue	5.0
Thymus	tissue	4.9
Spinal cord	tissue	4.8
Cerebellum	tissue	4.7
Midbrain	tissue	4.5
Substantia nigra	tissue	4.5
Medulla oblongata	tissue	4.4
Tonsil	tissue	4.4
Olfactory bulb	tissue	4.3
Lymph node	tissue	4.1
Cerebral cortex	tissue	4.0
Amygdala	tissue	4.0
Thalamus	tissue	4.0
Superior colliculi	tissue	4.0
Periaqueductal gray	tissue	4.0
Retrosplenial cortex	tissue	4.0
Pons	tissue	3.9
Hippocampal formation	tissue	3.9
Entorhinal cortex	tissue	3.9
Ventral forebrain	tissue	3.9
Septum	tissue	3.8
Temporal cortex	tissue	3.8
Basal ganglia	tissue	3.7
Hypothalamus	tissue	3.6
Occipital cortex	tissue	3.6
Insular cortex	tissue	3.6
Motor cortex	tissue	3.5
Somatosensory cortex	tissue	3.5
Retrosplenial and cingulate cortex	tissue	3.4
Prefrontal cortex	tissue	3.2
Skin 1	tissue	3.1
Rectum	tissue	2.7
Appendix	tissue	2.6
Duodenum	tissue	2.3
Esophagus	tissue	2.0
Colon	tissue	2.0
Retina	tissue	1.9
Placenta	tissue	1.9
Smooth muscle	tissue	1.8
Small intestine	tissue	1.8
Epididymis	tissue	1.5
Spleen	tissue	1.5
Ovary	tissue	1.3
Endometrium 1	tissue	1.3
Stomach 1	tissue	1.2
Testis	tissue	1.0
Urinary bladder	tissue	1.0
Gallbladder	tissue	1.0
Breast	tissue	0.9
Prostate	tissue	0.8
Adipose tissue	tissue	0.7
Lung	tissue	0.7
Liver	tissue	0.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (15.0), Temporal white matter (15.0), Flocculonodular lobe (14.9), Corpus callosum, splenium (white matter) (13.1), Vermis (12.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CENPI by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 51 miRNAs:

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

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000682095 — one region, missense o/e 0.83. DepMap (CRISPR cell-line fitness): dependent in 64.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H1944 (-1.631), MPP 89 (-1.46), HSC-2 (-1.295), Caki-2 (-1.292), AML-193 (-1.259), KP-N-YN (-1.242), NIH:OVCAR-3 (-1.239), SK-N-BE(2) (-1.234), NCI-H647 (-1.221), SK-N-AS (-1.21), KYM-1 (-1.167), OAW28 (-1.166), IMR-32 (-1.156), TUHR10TKB (-1.103), TEN (-1.093).

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

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q8AYS7	58.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ARL13A	protein-coding	392509
XKRX	protein-coding	402415
TMEM35A	protein-coding	59353
TRMT2B	protein-coding	79979
TAF7L	protein-coding	54457
DRP2	protein-coding	1821

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): A0A804HK71, A0A8C8KX99, Q92674, 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 (70 total): helix 43, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7PB4	Cenp-HIK 3-protein complex	X-RAY DIFFRACTION	2.49
28OP	Structure of the human inner kinetochore CCAN and CENP-C bound to DNA	ELECTRON MICROSCOPY	2.7
7R5S	Structure of the human CCAN bound to alpha satellite DNA	ELECTRON MICROSCOPY	2.83
7PKN	Structure of the human CCAN deltaCT complex	ELECTRON MICROSCOPY	3.2
7XHO	Structure of human inner kinetochore CCAN complex	ELECTRON MICROSCOPY	3.29
9TAW	Structure of the human inner kinetochore CCAN bound to DNA	ELECTRON MICROSCOPY	3.54
7XHN	Structure of human inner kinetochore CCAN-DNA complex	ELECTRON MICROSCOPY	3.71
7R5V	Structure of the human CCAN CENP-A alpha-satellite complex	ELECTRON MICROSCOPY	4.55
7QOO	Structure of the human inner kinetochore CCAN complex	ELECTRON MICROSCOPY	4.6
7YYH	Structure of the human CCANdeltaT CENP-A alpha-satellite complex	ELECTRON MICROSCOPY	8.9
7YWX	Structure of the human CCAN CENP-A alpha-satellite complex	ELECTRON MICROSCOPY	12
9TAY	Structure of the human inner kinetochore CCAN bound to a di-CENP-A nucleosome	ELECTRON MICROSCOPY	15.5

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies; nucleoplasm

Antibody reliability (HPA): IF supported

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 21; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

21 pathways:

ID	Pathway	Evidence
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	curated
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere	curated
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	curated
R-HSA-68877	Mitotic Prometaphase	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-2500257	Resolution of Sister Chromatid Cohesion	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-141424	Amplification of signal from the kinetochores	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-73886	Chromosome Maintenance	—
R-HSA-68886	M Phase	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-69618	Mitotic Spindle Checkpoint	—
R-HSA-774815	Nucleosome assembly	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
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 (4): mitotic sister chromatid segregation (GO:0000070), chromosome segregation (GO:0007059), sex differentiation (GO:0007548), CENP-A containing chromatin assembly (GO:0034080)

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

GO Cellular Component (7): 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)

Reactome top-level categories

14 top-level categories:

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

20 GO namespaces:

Category	Terms
intracellular membraneless organelle	2
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
kinetochore	CC	direct assay
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 16 of 2,227 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPI	CENPH	Q9H3R5	965
CENPI	CENPK	Q9BS16	955
CENPI	CENPA	P49450	940
CENPI	CENPT	Q96BT3	939
CENPI	CENPP	Q6IPU0	936
CENPI	CENPO	Q9BU64	932
CENPI	CENPU	Q71F23	930
CENPI	CENPQ	Q7L2Z9	930
CENPI	CENPL	Q8N0S6	929
CENPI	CENPM	Q9NSP4	921
CENPI	CENPN	Q96H22	916
CENPI	CENPC	Q03188	899
CENPI	ITGB3BP	Q13352	853
CENPI	CENPB	P07199	798
CENPI	CENPS	Q8N2Z9	792
CENPI	CENPF	P49454	792

IntAct

Human interaction partners of CENPI in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
CENPK	physical association	0.670	1
CEP76	physical association	0.560	3
NPM1	physical association	0.400	1
CENPM	association	0.350	1
SF1	physical association	0.000	1

BioGRID (56 interactions; top human partners by supporting records): CENPU (Affinity Capture-MS; 5 records), CENPH (Affinity Capture-MS; 3 records), CENPM (Affinity Capture-MS; 3 records), CENPA (Proximity Label-MS; 2 records), CENPK (Affinity Capture-MS; 2 records), CENPN (Affinity Capture-MS; 2 records), CENPO (Affinity Capture-MS; 2 records), CENPQ (Affinity Capture-MS; 2 records), DGCR8 (Affinity Capture-MS; 2 records), RBM34 (Affinity Capture-MS; 2 records), ZNF71 (Affinity Capture-MS; 2 records), APP (Reconstituted Complex), BRCA1 (Proximity Label-MS), C12orf49 (Negative Genetic), CENPL (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

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

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
CEN complex	37	SUPT16H, BMI1, CENPC, CENPU, FBL, RNF2, COBLL1, CUL4A, DDB1, HSPA5, NUP93, KIF23, ZFP91, CENPI, CENPK, RACGAP1, SSRP1, ZC3H13, CENPH, CENPM, HSPA8, VIRMA, CBX3, CENPB, SMARCA5, SRRT, CBX8, CENPA, CENPO, PLPPR3, RSF1, WDR11, WTAP, CENPL, DHX38, RING1, SHCBP1
CENP-A nucleosomal complex	15	CENPA, CENPH, CENPT, RSF1, CENPB, CENPL, CENPN, H2AC1, HJURP, SSRP1, SUPT16H, CENPC, CENPI, H4C1, H2BC3
CENP-H-I complex	11	CENPH, CENPI, CENPK, CENPM, CENPP, CENPU, CENPL, CENPN, CENPO, CENPQ, ITGB3BP

Disease & clinical

Genetic variants

Variant evidence for CENPI: 171 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	61
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
493606	GRCh37/hg19 Xq22.1(chrX:99742359-100759773)x3	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CENPI’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,870):

Position(s)	Effect	Δscore	Sites
X:101101056–101101057	acceptor_loss	1.0000	5
X:101102272–101102273	acceptor_loss	1.0000	5
X:101109889–101109890	acceptor_loss	1.0000	5
X:101109999–101110000	donor_loss	1.0000	5
X:101128837–101128838	donor_loss	1.0000	5
X:101129980–101129981	acceptor_loss	1.0000	5
X:101098527	donor_gain	0.9900
X:101101051	acceptor_gain	0.9900
X:101101057	acceptor_loss	0.9900
X:101101297–101101298	donor_loss	0.9900	5

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	7.44e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	8.43e-06
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	1.95e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	0.000101
Lung Adenocarcinoma (validation)	unfavorable	0.000114

Disease associations

OMIM: gene MIM:300065 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

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

Mondo (1): idiopathic steroid-sensitive nephrotic syndrome (MONDO:0019067)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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	decreases expression, increases abundance	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	decreases methylation, affects expression	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 abundance, increases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 82 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	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
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects
NCT02696889	Not specified	COMPLETED	Rejuvenation of Premature Ovarian Failure With Stem Cells
NCT02779374	Not specified	TERMINATED	Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency
NCT03207412	Not specified	UNKNOWN	Human Amniotic Epithelial Cells Treatment for Ovarian Insufficiency
NCT03381300	Not specified	ACTIVE_NOT_RECRUITING	Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
NCT03412487	Not specified	UNKNOWN	Ovarian Histopathology and Laparoscopic Assessment of Premature Ovarian Failure
NCT03474120	Not specified	UNKNOWN	Prospective Genetic Study in Patients With Ovarian Insufficiency
NCT03480412	Not specified	UNKNOWN	Second Step Protocol in Poor Ovarian Responder (POR)
NCT03542708	Not specified	COMPLETED	Injections of Autologous PRP in Women With Primary Ovarian Insufficiency
NCT03692572	Not specified	COMPLETED	Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
NCT03840824	Not specified	COMPLETED	Blood Spot Self-administered Test and Assay
NCT03861715	Not specified	UNKNOWN	Single Follicular Dexarelix for LH Suppression During Ovarian Stimulation in Oocyte Donors.
NCT03924648	Not specified	COMPLETED	Endocan Levels in Women With Premature Ovarian Insufficiency