CEP57

Summary

CEP57 (centrosomal protein 57, HGNC:30794) is a protein-coding gene on chromosome 11q21, encoding Centrosomal protein of 57 kDa (Q86XR8). Centrosomal protein which may be required for microtubule attachment to centrosomes.

This gene encodes a cytoplasmic protein called Translokin. This protein localizes to the centrosome and has a function in microtubular stabilization. The N-terminal half of this protein is required for its centrosome localization and for its multimerization, and the C-terminal half is required for nucleating, bundling and anchoring microtubules to the centrosomes. This protein specifically interacts with fibroblast growth factor 2 (FGF2), sorting nexin 6, Ran-binding protein M and the kinesins KIF3A and KIF3B, and thus mediates the nuclear translocation and mitogenic activity of the FGF2. It also interacts with cyclin D1 and controls nucleocytoplasmic distribution of the cyclin D1 in quiescent cells. This protein is crucial for maintaining correct chromosomal number during cell division. Mutations in this gene cause mosaic variegated aneuploidy syndrome, a rare autosomal recessive disorder. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 9702 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mosaic variegated aneuploidy syndrome 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 927 total — 15 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 93
• MANE Select transcript: NM_014679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30794
Approved symbol	CEP57
Name	centrosomal protein 57
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	Translokin, TSP57, KIAA0092
Ensembl gene	ENSG00000166037
Ensembl biotype	protein_coding
OMIM	607951
Entrez	9702

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 20 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000325486, ENST00000325542, ENST00000535224, ENST00000535497, ENST00000536587, ENST00000537093, ENST00000537677, ENST00000538095, ENST00000538158, ENST00000538658, ENST00000539855, ENST00000540830, ENST00000541150, ENST00000541365, ENST00000541768, ENST00000544522, ENST00000872215, ENST00000872216, ENST00000872217, ENST00000872218, ENST00000872219, ENST00000940390, ENST00000940391, ENST00000940392, ENST00000940393, ENST00000944617, ENST00000944618

RefSeq mRNA: 4 — MANE Select: NM_014679 NM_001243776, NM_001243777, NM_001363604, NM_014679

CCDS: CCDS58166, CCDS58167, CCDS8304, CCDS86240

Canonical transcript exons

ENST00000325542 — 11 exons

Exon	Start	End
ENSE00002261369	95831026	95832693
ENSE00002318837	95790498	95790743
ENSE00003461567	95821871	95821978
ENSE00003467967	95812932	95813111
ENSE00003540259	95799232	95799388
ENSE00003548316	95822499	95822576
ENSE00003597447	95829187	95829331
ENSE00003614619	95818827	95818904
ENSE00003662599	95813468	95813589
ENSE00003789629	95827786	95828027
ENSE00003791501	95817787	95817903

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.0636 / max 429.4280, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116320	34.7775	1820
116322	3.7246	1245
116321	0.7850	453
116323	0.5119	243
116319	0.2646	131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.98	gold quality
sperm	CL:0000019	95.67	gold quality
calcaneal tendon	UBERON:0003701	95.67	gold quality
ganglionic eminence	UBERON:0004023	95.02	gold quality
cortical plate	UBERON:0005343	94.51	gold quality
secondary oocyte	CL:0000655	94.17	gold quality
gall bladder	UBERON:0002110	93.86	gold quality
hair follicle	UBERON:0002073	93.85	gold quality
male germ cell	CL:0000015	93.83	gold quality
ventricular zone	UBERON:0003053	93.76	gold quality
choroid plexus epithelium	UBERON:0003911	93.18	gold quality
cartilage tissue	UBERON:0002418	92.71	gold quality
left testis	UBERON:0004533	92.69	gold quality
adrenal tissue	UBERON:0018303	92.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.53	gold quality
testis	UBERON:0000473	92.46	gold quality
embryo	UBERON:0000922	92.42	gold quality
right testis	UBERON:0004534	92.34	gold quality
sural nerve	UBERON:0015488	92.11	gold quality
tendon	UBERON:0000043	92.00	gold quality
cervix squamous epithelium	UBERON:0006922	91.92	silver quality
bone marrow cell	CL:0002092	91.87	gold quality
pancreatic ductal cell	CL:0002079	91.84	gold quality
right uterine tube	UBERON:0001302	91.40	gold quality
left ovary	UBERON:0002119	91.36	gold quality
body of pancreas	UBERON:0001150	91.21	gold quality
epithelium of nasopharynx	UBERON:0001951	91.07	gold quality
ovary	UBERON:0000992	90.93	gold quality
right lobe of liver	UBERON:0001114	90.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.90	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	1507.21
E-ANND-3	yes	8.08
E-MTAB-7303	no	654.27
E-MTAB-6142	no	205.71
E-GEOD-99795	no	129.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting CEP57, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-498-5P	99.76	69.64	1807

Literature-anchored findings (GeneRIF, showing 14)

• Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division. (PMID:21552266)
• Cep57 acts as a PCM component through binding to NEDD1 and is required for spindle microtubule organization and maintenance of spindle pole integrity. (PMID:22508265)
• Data suggest for therapeutic targeting of the FGF-2/FGFR1/CEP57 axis in prostate cancer. (PMID:23243019)
• Cep57, Cep63, and Cep152 are parts of a ring-like complex localizing around the proximal end of centrioles. (PMID:23333316)
• Cep57 is essential for cytokinesis via regulation of central spindle assembly and formation of the midbody (PMID:23569207)
• We identified copy number variation (CNV) deletion impacting the exon sequences of CEP57L1, present in the affected mother and her affected daughter (PMID:26561035)
• Cep57 is a mitotic kinetochore component that links the function of the KMN (KNL1/Mis12 complex/Ndc80 complex) network and spindle assembly checkpoint via Mis12 binding and Mad1-Mad2 interaction. (PMID:26743940)
• Depletion of Cep57 causes PCM disorganization and precocious centriole disengagement during mitosis. (PMID:30804344)
• Requirement of the Cep57-Cep63 Interaction for Proper Cep152 Recruitment and Centriole Duplication. (PMID:32152252)
• Follow-up of two adult brothers with homozygous CEP57 pathogenic variants expands the phenotype of Mosaic Variegated Aneuploidy Syndrome. (PMID:32861809)
• Cep57 and Cep57L1 maintain centriole engagement in interphase to ensure centriole duplication cycle. (PMID:33492359)
• Mosaic Variegated Aneuploidy syndrome 2 caused by biallelic variants in CEP57, two new cases and review of the phenotype. (PMID:34500087)
• Mosaic variegated aneuploidy syndrome 2 with biallelic novel CEP57 splice site variation in Indian siblings: Expanding the clinical and molecular spectrum. (PMID:36635612)
• Cep57 regulates human centrosomes through multivalent interactions. (PMID:38857398)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cep57	ENSMUSG00000031922
rattus_norvegicus	Cep57	ENSRNOG00000006792

Paralogs (1): CEP57L1 (ENSG00000183137)

Protein

Protein identifiers

Centrosomal protein of 57 kDa — Q86XR8 (reviewed: Q86XR8)

Alternative names: FGF2-interacting protein, Testis-specific protein 57, Translokin

All UniProt accessions (10): Q86XR8, F5GXS6, F5GYW0, F5GZ93, F5H0C6, F5H1B0, F5H6R3, F5H7J4, H0YFT8, H0YGT4

UniProt curated annotations — full annotation on UniProt →

Function. Centrosomal protein which may be required for microtubule attachment to centrosomes. May act by forming ring-like structures around microtubules. Mediates nuclear translocation and mitogenic activity of the internalized growth factor FGF2, but that of FGF1.

Subunit / interactions. Homodimer and homooligomer. Interacts with microtubules. Interacts with FGF2 and RAP80. Does not interact with FGF1 or FGF2 isoform 24 kDa.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Ubiquitous.

Disease relevance. Mosaic variegated aneuploidy syndrome 2 (MVA2) [MIM:614114] A severe developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal region mediates the interaction with microtubules and is able to nucleate and bundles microtubules in vitro. The centrosome localization domain (CLD) region mediates the localization to centrosomes and homooligomerization.

Similarity. Belongs to the translokin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q86XR8-1	1	yes
Q86XR8-2	2
Q86XR8-3	3
Q86XR8-4	4
Q86XR8-5	5

RefSeq proteins (4): NP_001230705, NP_001230706, NP_001350533, NP_055494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024957	Cep57_MT-bd_dom	Domain
IPR025913	Cep57_CLD	Domain
IPR051756	Centrosomal_MT-associated	Family

Pfam: PF06657, PF14073

UniProt features (27 total): region of interest 5, compositionally biased region 5, splice variant 5, sequence conflict 4, modified residue 2, helix 2, coiled-coil region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8IBH	X-RAY DIFFRACTION	2.1
4L0R	X-RAY DIFFRACTION	2.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XR8-F1	76.32	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 (2): 53, 55

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 402 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_MALE_GAMETE_GENERATION, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, GOCC_MICROTUBULE_ORGANIZING_CENTER, PUJANA_CHEK2_PCC_NETWORK, CREB_Q4, YGACNNYACAR_UNKNOWN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GNF2_ANP32B, GOBP_RESPONSE_TO_FIBROBLAST_GROWTH_FACTOR, GOCC_CENTROSOME, TGIF_01, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, DOUGLAS_BMI1_TARGETS_DN

GO Biological Process (3): spermatid development (GO:0007286), fibroblast growth factor receptor signaling pathway (GO:0008543), protein homooligomerization (GO:0051260)

GO Molecular Function (6): microtubule binding (GO:0008017), fibroblast growth factor binding (GO:0017134), protein homodimerization activity (GO:0042803), gamma-tubulin binding (GO:0043015), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (8): nucleus (GO:0005634), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), microtubule (GO:0005874), centriolar satellite (GO:0034451), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
tubulin binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
germ cell development	1
spermatid differentiation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
protein complex oligomerization	1
growth factor binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
protein binding	1
endomembrane system	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
centrosome	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP57	CEP63	Q96MT8	856
CEP57	TRIP13	Q15645	670
CEP57	BUB1B	O60566	663
CEP57	MYH11	P35749	647
CEP57	FGF1	P05230	631
CEP57	PLK4	O00444	623
CEP57	CEP152	O94986	622
CEP57	CEP135	Q66GS9	570
CEP57	FGF2	P09038	517
CEP57	CNTLN	Q9NXG0	507
CEP57	CEP192	Q8TEP8	491
CEP57	CEP290	O15078	487
CEP57	DEUP1	Q05D60	486
CEP57	TUBB6	Q9BUF5	479
CEP57	CEP164	Q9UPV0	478
CEP57	SASS6	Q6UVJ0	478

IntAct

74 interactions, top by confidence:

A	B	Type	Score
CEP57	GCC1	psi-mi:“MI:0915”(physical association)	0.740
CEP57	CEP63	psi-mi:“MI:0915”(physical association)	0.740
GCC1	CEP57	psi-mi:“MI:0915”(physical association)	0.740
CEP63	CEP57	psi-mi:“MI:0915”(physical association)	0.740
RALBP1	CEP57	psi-mi:“MI:0915”(physical association)	0.670
CEP57	TFIP11	psi-mi:“MI:0915”(physical association)	0.670
CEP57	RALBP1	psi-mi:“MI:0915”(physical association)	0.670
TFIP11	CEP57	psi-mi:“MI:0915”(physical association)	0.670
NAP1L5	IQGAP1	psi-mi:“MI:0914”(association)	0.640
CEP57	KRT13	psi-mi:“MI:0915”(physical association)	0.560
MIA2	CEP57	psi-mi:“MI:0915”(physical association)	0.560
CEP57	KRT15	psi-mi:“MI:0915”(physical association)	0.560
KRT31	CEP57	psi-mi:“MI:0915”(physical association)	0.560
CEP57	KRT40	psi-mi:“MI:0915”(physical association)	0.560
CEP57	MAGEA2B	psi-mi:“MI:0915”(physical association)	0.560
CEP57	MIA2	psi-mi:“MI:0915”(physical association)	0.560
KRT15	CEP57	psi-mi:“MI:0915”(physical association)	0.560
CEP57	KRT31	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (175): CEP57 (Two-hybrid), CEP57 (Two-hybrid), CEP57 (Two-hybrid), CEP57 (Two-hybrid), RALBP1 (Two-hybrid), TFIP11 (Two-hybrid), GCC1 (Two-hybrid), CEP63 (Two-hybrid), KRT40 (Two-hybrid), MAGEA2B (Two-hybrid), CEP57 (Affinity Capture-MS), CEP57 (Proximity Label-MS), CEP57 (Two-hybrid), CEP57 (Two-hybrid), CEP57 (Two-hybrid)

ESM2 similar proteins: A0JMQ7, A2BGP7, A4D2H0, A4FU28, B4F7A7, O75665, P0C219, P0CG41, Q05D60, Q15025, Q28BZ7, Q28C41, Q2T9X8, Q32LC2, Q499E4, Q4PJT6, Q4R7I4, Q5FWP9, Q5U3Z6, Q5U465, Q5XIA0, Q5XJA2, Q5ZJA3, Q6AXZ4, Q6NRH3, Q6P926, Q6PCG6, Q7M6Y5, Q80Z25, Q865V0, Q86UF2, Q86W54, Q86XR8, Q86YF9, Q86Z20, Q8BMD2, Q8CEE0, Q8IX94, Q8IYJ2, Q8IYX8

Diamond homologs: B4F7A7, Q28BZ7, Q5FWP9, Q6AXZ4, Q865V0, Q86XR8, Q8CEE0, Q8IYX8, Q8VDS7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	6
Uncertain significance	594
Likely benign	277
Benign	8

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1030345	NM_014679.5(CEP57):c.1015C>T (p.Arg339Ter)	Pathogenic
1421218	NM_014679.5(CEP57):c.523C>T (p.Arg175Ter)	Pathogenic
2169972	NM_014679.5(CEP57):c.20_21del (p.Ser7fs)	Pathogenic
2425964	NC_000011.9:g.(?95523863)(95564420_?)del	Pathogenic
2873280	NM_014679.5(CEP57):c.312_313del (p.Tyr104_Lys105delinsTer)	Pathogenic
30690	NM_014679.5(CEP57):c.520_521del (p.Glu174fs)	Pathogenic
30691	NM_014679.5(CEP57):c.915_925dup (p.Leu309fs)	Pathogenic
30692	NM_014679.5(CEP57):c.241C>T (p.Arg81Ter)	Pathogenic
3574131	NM_014679.5(CEP57):c.973C>T (p.Arg325Ter)	Pathogenic
431798	NM_014679.5(CEP57):c.724del (p.Arg242fs)	Pathogenic
4751150	NM_014679.5(CEP57):c.600del (p.Thr201fs)	Pathogenic
574305	NM_014679.5(CEP57):c.1117C>T (p.Gln373Ter)	Pathogenic
643769	NM_014679.5(CEP57):c.451C>T (p.Arg151Ter)	Pathogenic
936628	NM_014679.5(CEP57):c.778A>T (p.Lys260Ter)	Pathogenic
977798	NM_014679.5(CEP57):c.382+2T>C	Pathogenic
2161490	NM_014679.5(CEP57):c.46-2A>T	Likely pathogenic
2425963	NC_000011.9:g.(?95549619)(95562458_?)del	Likely pathogenic
2828215	NM_014679.5(CEP57):c.622-2A>G	Likely pathogenic
2884194	NM_014679.5(CEP57):c.699+1G>T	Likely pathogenic
3336980	NM_014679.5(CEP57):c.1388_1391del (p.Lys463fs)	Likely pathogenic
638495	NM_014679.5(CEP57):c.1402del (p.Lys467_Leu468insTer)	Likely pathogenic

SpliceAI

1836 predictions. Top by Δscore:

Variant	Effect	Δscore
11:95799230:A:AG	acceptor_gain	1.0000
11:95799231:G:GA	acceptor_gain	1.0000
11:95799231:GA:G	acceptor_gain	1.0000
11:95799231:GAAC:G	acceptor_gain	1.0000
11:95799231:GAACA:G	acceptor_gain	1.0000
11:95799350:G:GG	donor_gain	1.0000
11:95799386:GAG:G	donor_gain	1.0000
11:95812930:A:AG	acceptor_gain	1.0000
11:95812931:G:GG	acceptor_gain	1.0000
11:95812931:GCC:G	acceptor_gain	1.0000
11:95812931:GCCAT:G	acceptor_gain	1.0000
11:95813107:TCAAG:T	donor_loss	1.0000
11:95813108:CAAGG:C	donor_loss	1.0000
11:95813109:AAGGT:A	donor_loss	1.0000
11:95813110:AGGTT:A	donor_loss	1.0000
11:95813112:G:GA	donor_loss	1.0000
11:95813113:T:A	donor_loss	1.0000
11:95813466:A:AG	acceptor_gain	1.0000
11:95813467:G:GG	acceptor_gain	1.0000
11:95813467:GA:G	acceptor_gain	1.0000
11:95813585:AACAA:A	donor_gain	1.0000
11:95813586:ACAA:A	donor_gain	1.0000
11:95813586:ACAAG:A	donor_loss	1.0000
11:95813587:CAA:C	donor_gain	1.0000
11:95813588:AA:A	donor_gain	1.0000
11:95813589:AG:A	donor_loss	1.0000
11:95813590:G:A	donor_loss	1.0000
11:95813590:GTAA:G	donor_gain	1.0000
11:95813591:T:A	donor_loss	1.0000
11:95817864:G:GT	donor_gain	1.0000

AlphaMissense

3314 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:95812956:T:C	L76P	1.000
11:95812947:T:A	L73H	0.999
11:95812947:T:C	L73P	0.999
11:95812997:G:C	A90P	0.999
11:95812935:T:A	I69K	0.998
11:95812956:T:A	L76H	0.998
11:95812977:T:C	L83S	0.998
11:95813491:G:C	A136P	0.998
11:95822562:T:C	F291L	0.998
11:95822564:T:A	F291L	0.998
11:95822564:T:G	F291L	0.998
11:95812943:G:C	A72P	0.997
11:95812944:C:A	A72D	0.997
11:95812990:G:C	R87S	0.997
11:95812990:G:T	R87S	0.997
11:95827798:A:C	S300R	0.997
11:95827800:C:A	S300R	0.997
11:95827800:C:G	S300R	0.997
11:95813537:G:C	R151P	0.996
11:95813554:G:C	A157P	0.996
11:95812935:T:C	I69T	0.995
11:95812935:T:G	I69R	0.995
11:95812956:T:G	L76R	0.995
11:95812959:A:C	Q77P	0.995
11:95812966:G:C	K79N	0.995
11:95812966:G:T	K79N	0.995
11:95812968:T:C	I80T	0.995
11:95812971:G:C	R81P	0.995
11:95813513:T:C	L143S	0.995
11:95812977:T:G	L83W	0.994

dbSNP variants (sampled 300 via entrez): RS1000024905 (11:95801450 C>A), RS1000074732 (11:95828506 C>T), RS1000175218 (11:95807166 G>A), RS1000322965 (11:95806762 C>T), RS1000416925 (11:95789934 G>A,T), RS1000450662 (11:95801842 G>A), RS1000462208 (11:95832546 T>C), RS1000495282 (11:95817224 G>A), RS1000505841 (11:95790645 C>T), RS1000547593 (11:95819909 TG>T), RS1000593866 (11:95824161 A>C), RS1000810365 (11:95832910 A>G), RS1000860780 (11:95801439 A>G), RS1000868060 (11:95797447 C>A), RS1000878381 (11:95791091 G>A)

Disease associations

OMIM: gene MIM:607951 | disease phenotypes: MIM:614114, MIM:257300

GenCC curated gene-disease

Disease	Classification	Inheritance
mosaic variegated aneuploidy syndrome 2	Definitive	Autosomal recessive
mosaic variegated aneuploidy syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mosaic variegated aneuploidy syndrome 2	Definitive	AR

Mondo (3): mosaic variegated aneuploidy syndrome 2 (MONDO:0013582), mosaic variegated aneuploidy syndrome 1 (MONDO:0009759), mosaic variegated aneuploidy syndrome (MONDO:0000141)

Orphanet (1): Mosaic variegated aneuploidy syndrome (Orphanet:1052)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000062	Ambiguous genitalia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000445	Wide nose
HP:0000457	Depressed nasal ridge
HP:0000478	Abnormality of the eye
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000601	Hypotelorism
HP:0000821	Hypothyroidism
HP:0000824	Decreased response to growth hormone stimulation test

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002318_10	Rheumatoid arthritis	4.000000e-09
GCST002318_67	Rheumatoid arthritis	1.000000e-11
GCST005141_9	Cognitive ability (MTAG)	2.000000e-09
GCST005316_363	Intelligence (MTAG)	1.000000e-09
GCST006218_23	Erosive tooth wear (severe vs non-severe)	1.000000e-08
GCST006950_5	Feeling worry	2.000000e-08
GCST006959_101	Rheumatoid arthritis	3.000000e-08
GCST009615_13	Triglyceride levels x loop diuretics use interaction	1.000000e-06
GCST011534_2	Sun-seeking behavior	4.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009589	worry measurement
EFO:0004530	triglyceride measurement
EFO:0010729	sun exposure measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536987	Mosaic variegated aneuploidy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
Cyclosporine	increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	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	decreases expression, affects cotreatment	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	decreases methylation, affects cotreatment	1

Cellosaurus cell lines

4 cell lines: 3 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1NA	Abcam HeLa CEP57 KO	Cancer cell line	Female
CVCL_CZ81	GM21656	Transformed cell line	Female
CVCL_EG00	GM21654	Transformed cell line	Male
CVCL_EG01	GM21655	Transformed cell line	Female

Clinical trials (associated diseases)

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