CENPH

Summary

CENPH (centromere protein H, HGNC:17268) is a protein-coding gene on chromosome 5q13.2, encoding Centromere protein H (Q9H3R5). Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. It is a selective cancer dependency (DepMap: 76.3% of cell lines).

Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. It localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex.

Source: NCBI Gene 64946 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• Cancer dependency (DepMap): dependent in 76.3% of screened cell lines
• MANE Select transcript: NM_022909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17268
Approved symbol	CENPH
Name	centromere protein H
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153044
Ensembl biotype	protein_coding
OMIM	605607
Entrez	64946

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000283006, ENST00000502689, ENST00000510742, ENST00000513575, ENST00000514753, ENST00000515001, ENST00000935971, ENST00000935972, ENST00000935973, ENST00000952160

RefSeq mRNA: 1 — MANE Select: NM_022909 NM_022909

CCDS: CCDS3998

Canonical transcript exons

ENST00000283006 — 9 exons

Exon	Start	End
ENSE00001008501	69189583	69189768
ENSE00001008502	69202919	69202970
ENSE00001082754	69208196	69208359
ENSE00001082755	69209707	69210357
ENSE00003495355	69191795	69191850
ENSE00003590246	69195717	69195791
ENSE00003600749	69202506	69202569
ENSE00003656074	69194647	69194695
ENSE00003686738	69197053	69197109

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 95.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7034 / max 553.0513, expressed in 1730 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56836	18.5375	1715
56837	4.1659	1039

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.94	gold quality
ventricular zone	UBERON:0003053	94.89	gold quality
ganglionic eminence	UBERON:0004023	94.87	gold quality
oocyte	CL:0000023	89.89	gold quality
right testis	UBERON:0004534	89.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.69	gold quality
left testis	UBERON:0004533	88.26	gold quality
testis	UBERON:0000473	87.64	gold quality
cortical plate	UBERON:0005343	87.47	gold quality
secondary oocyte	CL:0000655	86.61	gold quality
bone marrow	UBERON:0002371	82.95	gold quality
calcaneal tendon	UBERON:0003701	81.66	gold quality
rectum	UBERON:0001052	80.42	gold quality
stromal cell of endometrium	CL:0002255	79.25	gold quality
vermiform appendix	UBERON:0001154	79.09	gold quality
esophagus mucosa	UBERON:0002469	78.09	gold quality
mucosa of transverse colon	UBERON:0004991	78.02	gold quality
gingival epithelium	UBERON:0001949	78.00	silver quality
buccal mucosa cell	CL:0002336	77.66	gold quality
lymph node	UBERON:0000029	77.39	gold quality
bone marrow cell	CL:0002092	77.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.05	gold quality
lower esophagus mucosa	UBERON:0035834	77.04	gold quality
upper arm skin	UBERON:0004263	76.78	gold quality
granulocyte	CL:0000094	76.00	gold quality
smooth muscle tissue	UBERON:0001135	75.38	gold quality
gingiva	UBERON:0001828	75.30	silver quality
skin of abdomen	UBERON:0001416	74.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.52	gold quality
muscle of leg	UBERON:0001383	74.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-99795	yes	97.67
E-HCAD-10	yes	36.19
E-GEOD-134144	yes	27.07
E-ANND-3	yes	7.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

32 targeting CENPH, 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-3613-3P	100.00	76.36	7965
HSA-MIR-196A-1-3P	99.99	72.15	2772
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-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-4791	96.51	67.76	659
HSA-MIR-4301	95.00	65.22	554

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 76.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• CENP-H is up-regulated and plays an important role in the aneuploidy frequently observed in colorectal cancers. (PMID:15930286)
• The CENP-H-I complex may function, in part, as a marker directing CENP-A deposition to centromeres. (PMID:16622420)
• has an important impact on the architecture and function of the human kinetochore complex (PMID:16875666)
• CENP-H has a role in preventing progression of nasopharyngeal carcinoma (PMID:17255272)
• CENP-C and CENP-H co-localize to the CENP-A chromatin domain. (PMID:17651496)
• the vertebrate KNL1 counterpart is essential for chromosome segregation and is required to localize a subset of outer kinetochore proteins. (PMID:18045986)
• CENP-H protein has a role in esophageal carcinoma progression (PMID:18700042)
• expression of CENPH was much higher in cancer cell lines & lung cancer tissue than normal cells & adjacent noncancerous lung tissues; results show that high CENPH protein expression was related to poor outcome in patients with nonsmall cell lung cancer (PMID:19170237)
• TRIM36 has a ubiquitin ligase activity and interacts with centromere protein-H. (PMID:19232519)
• Upregulation of CENP-H in tongue cancer is associated with disease progression. (PMID:19500341)
• CENP-H-containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1. (PMID:19625449)
• Breast cancer patients with high CENP-H expression had short overall survival. CENP-H expression was related with clinical stage. (PMID:21880184)
• CENP-H promotes the proliferation of human gastric cancer cells (PMID:22381774)
• upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in hypopharyngeal squamous cell carcinoma (HSSC); these factors may be predictors of a relapsing phenotype in HSSC cases (PMID:22631655)
• Sp1 and Sp3 bind to the CENPH minimal promoter and function as a regulator of the transcription of CENPH in nasopharyngeal carcinomas. (PMID:22682030)
• High expression of CENP-H in gastric cancer indicates poor prognosis and Survivin may mediate its procancer role. (PMID:22999412)
• CENP-H was overexpressed in HCC, and its level of upregulation was an independent prognostic indicator, suggesting that CENP-H may be an effective therapeutic strategy for the treatment of HCC. (PMID:23970101)
• Upregulation of centromere protein H is associated with progression of renal cell carcinoma (PMID:26248586)
• propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kinetochore microtubule dynamics for accurate chromosome segregation (PMID:26378239)
• In summary, CENP-H may be involved in cell proliferation and apoptosis of hepatocellular carcinoma (HCC)cells through the mitochondrial apoptotic pathway. Combined with previous studies, the data provide a new perspective on HCC development and progression. (PMID:28498417)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cenph	ENSDARG00000094892
mus_musculus	Cenph	ENSMUSG00000045273
rattus_norvegicus	Cenph	ENSRNOG00000018615

Protein

Protein identifiers

Centromere protein H — Q9H3R5 (reviewed: Q9H3R5)

Alternative names: Interphase centromere complex protein 35

All UniProt accessions (4): Q9H3R5, A0A0S2Z5T0, B3KVZ3, H0Y9E6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.

Subunit / interactions. Self-associates. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. Interacts directly with CENPK. Interacts with KIF2C and NDC80. Interacts with TRIM36.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Similarity. Belongs to the CENP-H/MCM16 family.

RefSeq proteins (1): NP_075060* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008426	CENP-H_C	Domain
IPR040034	CENP-H	Family

Pfam: PF05837

UniProt features (21 total): helix 6, turn 4, modified residue 3, compositionally biased region 2, chain 1, region of interest 1, coiled-coil region 1, strand 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

13 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
9TAX	ELECTRON MICROSCOPY	4.5
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-Q9H3R5-F1	82.95	0.49

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 (4): 1, 16, 68, 67

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: 191 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_CHROMOSOME_ORGANIZATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, KONG_E2F3_TARGETS, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, AFFAR_YY1_TARGETS_DN, KUNINGER_IGF1_VS_PDGFB_TARGETS_DN, FISCHER_DREAM_TARGETS, GOBP_KINETOCHORE_ORGANIZATION, REACTOME_CELL_CYCLE_CHECKPOINTS

GO Biological Process (4): mitotic spindle organization (GO:0007052), chromosome segregation (GO:0007059), kinetochore assembly (GO:0051382), kinetochore organization (GO:0051383)

GO Molecular Function (2): kinetochore binding (GO:0043515), protein binding (GO:0005515)

GO Cellular Component (8): kinetochore (GO:0000776), inner kinetochore (GO:0000939), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytosol (GO:0005829), chromosome, centromeric region (GO:0000775)

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
binding	2
nuclear lumen	2
cellular anatomical structure	2
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell cycle process	1
kinetochore organization	1
protein-containing complex assembly	1
membraneless organelle assembly	1
chromosome organization	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
cytoplasm	1
chromosomal region	1

Protein interactions and networks

STRING

1567 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPH	CENPM	Q9NSP4	999
CENPH	CENPI	Q92674	999
CENPH	CENPK	Q9BS16	999
CENPH	CENPC	Q03188	995
CENPH	CENPU	Q71F23	992
CENPH	CENPA	P49450	989
CENPH	CENPL	Q8N0S6	988
CENPH	CENPN	Q96H22	988
CENPH	CENPT	Q96BT3	986
CENPH	CENPO	Q9BU64	985
CENPH	CENPP	Q6IPU0	971
CENPH	CENPQ	Q7L2Z9	964
CENPH	CENPS	Q8N2Z9	939
CENPH	NUF2	Q9BZD4	932
CENPH	CENPB	P07199	931

IntAct

154 interactions, top by confidence:

A	B	Type	Score
CENPK	CENPH	psi-mi:“MI:0915”(physical association)	0.870
CENPH	CENPK	psi-mi:“MI:0915”(physical association)	0.870
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
CENPH	NDC80	psi-mi:“MI:0915”(physical association)	0.800
NDC80	CENPH	psi-mi:“MI:0915”(physical association)	0.800
CENPH	NDC80	psi-mi:“MI:0914”(association)	0.800
TEKT2	CEP170	psi-mi:“MI:0914”(association)	0.730
SPAG5	CENPH	psi-mi:“MI:0915”(physical association)	0.670
H2AP	CENPH	psi-mi:“MI:0915”(physical association)	0.670
RASSF7	SNAP29	psi-mi:“MI:0914”(association)	0.660
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
CENPH	MTAP	psi-mi:“MI:0915”(physical association)	0.560
MTAP	CENPH	psi-mi:“MI:0915”(physical association)	0.560
CENPH	ABI2	psi-mi:“MI:0915”(physical association)	0.560
LMNB1	CENPH	psi-mi:“MI:0915”(physical association)	0.560
DCTN2	CENPH	psi-mi:“MI:0915”(physical association)	0.560
ERH	CENPH	psi-mi:“MI:0915”(physical association)	0.560
NUP54	CENPH	psi-mi:“MI:0915”(physical association)	0.560
C1orf216	CENPH	psi-mi:“MI:0915”(physical association)	0.560
ZNF493	CENPH	psi-mi:“MI:0915”(physical association)	0.560
CCDC146	CENPH	psi-mi:“MI:0915”(physical association)	0.560
C8orf58	CENPH	psi-mi:“MI:0915”(physical association)	0.560
MESD	CENPH	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN12	CENPH	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (149): CENPH (Two-hybrid), CENPH (Two-hybrid), CENPH (Two-hybrid), CENPH (Affinity Capture-MS), CENPH (Affinity Capture-MS), CENPH (Affinity Capture-MS), CENPH (Affinity Capture-MS), CENPH (Affinity Capture-MS), CENPH (Proximity Label-MS), CENPH (Proximity Label-MS), CENPH (Proximity Label-MS), CENPH (Proximity Label-MS), CENPH (Affinity Capture-MS), CENPH (Affinity Capture-MS), CENPH (Affinity Capture-MS)

ESM2 similar proteins: A0JMY4, A2AJB1, A3KQH2, A7RNG8, B1H228, E9Q9F7, F1N2N9, F1RKB1, M1V4Y8, Q0VFX2, Q16VW9, Q17QH9, Q28G12, Q2TA00, Q2TAA8, Q3KPZ2, Q3SZX9, Q3T0L1, Q3USS3, Q3UX62, Q3UZ57, Q4R6I5, Q4R8Y5, Q4V7B0, Q502W7, Q5T1B0, Q5T5S1, Q5XIR6, Q5XIR8, Q66H60, Q68CZ6, Q6DCY9, Q6DHI2, Q6PA15, Q8BSN3, Q8C5T8, Q8CDN8, Q8CDV6, Q8IWF9, Q8NA47

Diamond homologs: Q3T0L1, Q90ZF9, Q9H3R5, Q9QYM8

SIGNOR signaling

1 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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	57.7×	2e-10
Chromosome Maintenance	8	25.6×	1e-07
Amplification of signal from the kinetochores	8	23.9×	2e-07
Deposition of new CENPA-containing nucleosomes at the centromere	8	19.2×	4e-07
Mitotic Spindle Checkpoint	8	19.2×	4e-07
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	9	15.9×	4e-07
Mitotic Metaphase and Anaphase	9	13.2×	1e-06
Mitotic Anaphase	9	13.2×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitotic sister chromatid segregation	5	23.4×	5e-04
chromosome segregation	10	16.9×	2e-07
mitotic spindle organization	5	13.2×	6e-03
cilium assembly	12	8.6×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1391 predictions. Top by Δscore:

Variant	Effect	Δscore
5:69191783:A:AG	acceptor_gain	1.0000
5:69191783:ATCT:A	acceptor_gain	1.0000
5:69191786:T:A	acceptor_gain	1.0000
5:69191789:TTTCA:T	acceptor_loss	1.0000
5:69191790:TTCA:T	acceptor_loss	1.0000
5:69191791:TCA:T	acceptor_loss	1.0000
5:69191792:CAG:C	acceptor_loss	1.0000
5:69191793:A:AG	acceptor_gain	1.0000
5:69191793:AG:A	acceptor_gain	1.0000
5:69191793:AGGCT:A	acceptor_gain	1.0000
5:69191794:G:GC	acceptor_gain	1.0000
5:69191794:GG:G	acceptor_gain	1.0000
5:69191794:GGC:G	acceptor_gain	1.0000
5:69191794:GGCT:G	acceptor_gain	1.0000
5:69191794:GGCTG:G	acceptor_gain	1.0000
5:69191847:GCAA:G	donor_gain	1.0000
5:69191848:CAA:C	donor_gain	1.0000
5:69191849:AA:A	donor_gain	1.0000
5:69191849:AAGT:A	donor_loss	1.0000
5:69191850:AG:A	donor_loss	1.0000
5:69191851:G:A	donor_loss	1.0000
5:69191851:G:GG	donor_gain	1.0000
5:69191852:TAA:T	donor_loss	1.0000
5:69191853:AA:A	donor_loss	1.0000
5:69194691:GAAGC:G	donor_gain	1.0000
5:69194693:AGC:A	donor_gain	1.0000
5:69194694:GC:G	donor_gain	1.0000
5:69194694:GCG:G	donor_gain	1.0000
5:69194696:G:GG	donor_gain	1.0000
5:69195715:A:AG	acceptor_gain	1.0000

AlphaMissense

1657 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:69209734:T:A	W227R	0.976
5:69209734:T:C	W227R	0.976
5:69209736:G:C	W227C	0.973
5:69209736:G:T	W227C	0.973
5:69209711:T:C	L219P	0.945
5:69208313:T:C	L202P	0.918
5:69191821:T:C	L54P	0.913
5:69202944:T:C	L154P	0.913
5:69209735:G:C	W227S	0.913
5:69209722:A:C	S223R	0.906
5:69209724:T:A	S223R	0.906
5:69209724:T:G	S223R	0.906
5:69209765:T:A	V237D	0.897
5:69191797:T:C	L46P	0.893
5:69209774:T:C	L240P	0.893
5:69208359:G:C	Q217H	0.892
5:69208359:G:T	Q217H	0.892
5:69209720:G:A	G222E	0.888
5:69209719:G:A	G222R	0.884
5:69209719:G:C	G222R	0.884
5:69202541:T:C	L136P	0.881
5:69208203:A:C	K165N	0.880
5:69208203:A:T	K165N	0.880
5:69197073:T:C	L112P	0.877
5:69209737:G:C	A228P	0.875
5:69209719:G:T	G222W	0.871
5:69202966:A:C	R161S	0.869
5:69202966:A:T	R161S	0.869
5:69209768:T:C	L238P	0.862
5:69208210:T:C	S168P	0.861

dbSNP variants (sampled 300 via entrez): RS1000100692 (5:69197994 C>T), RS1000265076 (5:69199844 G>A), RS1000318035 (5:69200053 C>G,T), RS1000455875 (5:69206565 T>C,G), RS1000534697 (5:69197797 TATA>T), RS1000623805 (5:69201785 G>A), RS1000785207 (5:69207694 A>G), RS1000923316 (5:69192172 T>A,G), RS1001017407 (5:69194730 T>A,C), RS1001162910 (5:69205344 C>T), RS1001196160 (5:69207912 C>T), RS1001275324 (5:69198311 T>G), RS1001306656 (5:69207154 T>C), RS1001377717 (5:69192610 C>G), RS1001407113 (5:69192308 T>A)

Disease associations

OMIM: gene MIM:605607 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, increases methylation	3
Valproic Acid	affects expression, decreases expression	3
Cyclosporine	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
trichostatin A	decreases expression, affects cotreatment	1
arsenite	increases reaction, affects binding	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
chromium hexavalent ion	decreases expression, increases abundance	1
azoxystrobin	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	decreases expression	1
Azathioprine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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