C10orf90

Summary

C10orf90 (chromosome 10 open reading frame 90, HGNC:26563) is a protein-coding gene on chromosome 10q26.2, encoding (E2-independent) E3 ubiquitin-conjugating enzyme FATS (Q96M02). Tumor suppressor that is required to sustain G2/M checkpoint after DNA damage.

Predicted to enable histone deacetylase binding activity and ubiquitin protein ligase activity. Predicted to be involved in several processes, including protein stabilization; regulation of cell cycle process; and response to ionizing radiation. Located in cytoskeleton; cytosol; and nucleoplasm.

Source: NCBI Gene 118611 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• MANE Select transcript: NM_001350921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26563
Approved symbol	C10orf90
Name	chromosome 10 open reading frame 90
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32938, bA422P15.2, FATS
Ensembl gene	ENSG00000154493
Ensembl biotype	protein_coding
OMIM	617735
Entrez	118611

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000284694, ENST00000356858, ENST00000368674, ENST00000424927, ENST00000432642, ENST00000463082, ENST00000480379, ENST00000488181, ENST00000657225

RefSeq mRNA: 3 — MANE Select: NM_001350921 NM_001004298, NM_001350921, NM_001350922

CCDS: CCDS31310, CCDS91374

Canonical transcript exons

ENST00000488181 — 10 exons

Exon	Start	End
ENSE00001099957	126464696	126464986
ENSE00001378502	126424997	126425902
ENSE00001954214	126670241	126670693
ENSE00003531381	126461401	126461585
ENSE00003540374	126513848	126513939
ENSE00003614993	126646565	126646637
ENSE00003625141	126459040	126459217
ENSE00003657782	126429787	126429850
ENSE00003663137	126425991	126426090
ENSE00003682694	126503957	126505085

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 89.55.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0456 / max 2279.5144, expressed in 197 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111977	2.1832	107
111980	0.6046	94
111971	0.5821	114
111981	0.4850	73
111966	0.3095	97
111972	0.1391	79
111979	0.1293	49
111976	0.1205	78
111974	0.1035	59
111967	0.0826	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	89.55	gold quality
corpus callosum	UBERON:0002336	89.18	gold quality
spinal cord	UBERON:0002240	87.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.01	gold quality
substantia nigra	UBERON:0002038	82.19	gold quality
midbrain	UBERON:0001891	80.76	gold quality
putamen	UBERON:0001874	80.31	gold quality
amygdala	UBERON:0001876	79.63	gold quality
medial globus pallidus	UBERON:0002477	79.21	gold quality
globus pallidus	UBERON:0001875	78.57	gold quality
inferior vagus X ganglion	UBERON:0005363	78.48	gold quality
caudate nucleus	UBERON:0001873	77.32	gold quality
hypothalamus	UBERON:0001898	76.76	gold quality
Ammon’s horn	UBERON:0001954	76.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.52	gold quality
parotid gland	UBERON:0001831	75.45	gold quality
prefrontal cortex	UBERON:0000451	74.93	gold quality
lateral globus pallidus	UBERON:0002476	74.64	gold quality
nucleus accumbens	UBERON:0001882	74.50	gold quality
subthalamic nucleus	UBERON:0001906	74.08	gold quality
temporal lobe	UBERON:0001871	73.36	gold quality
left testis	UBERON:0004533	73.03	gold quality
right frontal lobe	UBERON:0002810	72.95	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.44	gold quality
frontal cortex	UBERON:0001870	72.22	gold quality
right testis	UBERON:0004534	72.20	gold quality
anterior cingulate cortex	UBERON:0009835	72.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.98	gold quality
testis	UBERON:0000473	71.64	gold quality
cerebral cortex	UBERON:0000956	71.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	84.42
E-HCAD-25	yes	55.54
E-ANND-3	yes	4.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

68 targeting C10orf90, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613

Literature-anchored findings (GeneRIF, showing 6)

• data suggest centrosomal functions for C10orf90 and KIAA1731 and new centriole-related functions for ALMS1 (PMID:20844083)
• FATS is involved in the carcinogenesis and development of breast cancer and could be a potential biomarker and prognostic factor for breast cancer therapy. (PMID:22040499)
• FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. (PMID:24240685)
• Data identified a genetic variant in the FATS gene (905C > T, 262D/N) that is associated with susceptibility to breast cancer in a parity-dependent manner. (PMID:26223354)
• FATS status is a biomarker in breast cancer to identify individuals likely to benefit from radiotherapy (PMID:28402275)
• The expression of FATS protein is associated with the development and is an independent prognostic factor of non-small cell lung cancer patients. (PMID:31770849)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	D7Ertd443e	ENSMUSG00000030994
rattus_norvegicus	C1h10orf90	ENSRNOG00000027542

Paralogs (3): ALMS1 (ENSG00000116127), CEP295 (ENSG00000166004), CEP295NL (ENSG00000178404)

Protein

Protein identifiers

(E2-independent) E3 ubiquitin-conjugating enzyme FATS — Q96M02 (reviewed: Q96M02)

Alternative names: Centrosomal protein C10orf90, E2/E3 hybrid ubiquitin-protein ligase FATS, Fragile-site associated tumor suppressor homolog

All UniProt accessions (7): Q96M02, A0A0A0MSX2, A0A0C4DGS3, H7C3F8, Q5T025, S4R3N7, S4R3Q7

UniProt curated annotations — full annotation on UniProt →

Function. Tumor suppressor that is required to sustain G2/M checkpoint after DNA damage. Acts as a p53/TP53 activator by inhibiting MDM2 binding to p53/TP53 and stimulating non-proteolytic polyubiquitination of p53/TP53. Exhibits ubiquitin ligase (E3) activity and assemble ubiquitin polymers through ‘Lys-11’- (K11-), ‘Lys-29’- (K29-) and ‘Lys-63’- (K63)-linkages, independently of the ubiquitin-conjugating enzyme (E2). Promotes p53/TP53-dependent transcription of CDKN1A/p21, leading to robust checkpoint response. Mediates CDKN1A/p21 protein stability in a ubiquitin-independent manner. Interacts with HDAC1 and prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21. May have a role in the assembly of primary cilia.

Subunit / interactions. Interacts with HDAC1; the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21. Interacts with p53/TP53; the interaction inhibits binding of p53/TP53 and MDM2.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96M02-1	1	yes
Q96M02-2	2

RefSeq proteins (3): NP_001004298, NP_001337850, NP_001337851 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029299	ALMS_motif	Domain
IPR041179	C10orf90_N	Domain

Pfam: PF15309, PF17730

UniProt features (16 total): region of interest 6, sequence variant 4, compositionally biased region 3, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96M02-F1	47.67	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_CENTRIOLE_REPLICATION, GOBP_CENTRIOLE_ASSEMBLY, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_REGULATION_OF_CENTROSOME_CYCLE, GOBP_ORGANELLE_ASSEMBLY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (4): protein polyubiquitination (GO:0000209), protein ubiquitination (GO:0016567), regulation of centriole replication (GO:0046599), protein stabilization (GO:0050821)

GO Molecular Function (2): ubiquitin protein ligase activity (GO:0061630), transferase activity (GO:0016740)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule organizing center	2
intracellular membraneless organelle	2
protein ubiquitination	1
protein modification by small protein conjugation	1
centriole replication	1
regulation of centrosome duplication	1
regulation of organelle assembly	1
regulation of protein stability	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
cytoplasm	1
cytoskeleton	1

Protein interactions and networks

STRING

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C10orf90	DOCK1	Q14185	838
C10orf90	CEP295	Q9C0D2	442
C10orf90	CALY	Q9NYX4	419
C10orf90	OR8B12	Q8NGG6	404
C10orf90	SMIM19	Q96E16	400
C10orf90	NEURL1	O76050	371
C10orf90	SLX4IP	Q5VYV7	370
C10orf90	OR8B3	Q8NGG8	370
C10orf90	GPR15LG	Q6UWK7	357
C10orf90	SH2D4B	Q5SQS7	348
C10orf90	CLRN2	A0PK11	320
C10orf90	MCRIP1	C9JLW8	308
C10orf90	BTBD16	Q32M84	290
C10orf90	DMBT1	Q9UGM3	285
C10orf90	ARL9	Q6T311	284

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MTNR1A	C10orf90	psi-mi:“MI:0915”(physical association)	0.370
GSK3B	C10orf90	psi-mi:“MI:0915”(physical association)	0.370
C10orf90	GPR150	psi-mi:“MI:0914”(association)	0.350
N		psi-mi:“MI:0914”(association)	0.350

BioGRID (16): C10orf90 (Affinity Capture-Western), TP53 (Biochemical Activity), C10orf90 (Two-hybrid), C10orf90 (Positive Genetic), C10orf90 (Two-hybrid), ESR2 (Affinity Capture-Western), C10orf90 (Affinity Capture-Western), GPR150 (Affinity Capture-MS), PDLIM7 (Affinity Capture-MS), C10orf90 (Cross-Linking-MS (XL-MS)), IGF2R (Cross-Linking-MS (XL-MS)), C10orf90 (Affinity Capture-MS), C10orf90 (Affinity Capture-MS), TP53 (Affinity Capture-Western), TP53 (Reconstituted Complex)

ESM2 similar proteins: A2ADZ8, A6NNH2, D2J0Y4, D3YU32, P0C2Y1, Q0VET5, Q12802, Q14676, Q149B8, Q283Q6, Q2TBI7, Q3KR64, Q3U0P1, Q4KMZ1, Q4R736, Q5QJ38, Q5R5G4, Q5T1N1, Q5TM68, Q5VWK0, Q5VYM1, Q5ZK13, Q68A65, Q6AZ54, Q6NXZ1, Q6PG16, Q6PIX9, Q7YR40, Q7Z572, Q86Y26, Q8BHP2, Q8BHW6, Q8C0D9, Q8C5V8, Q8C9M2, Q8CGM2, Q8N5Q1, Q8NCD3, Q8WP21, Q924C5

Diamond homologs: D2J0Y4, Q8K4E0, Q8TCU4, Q96M02

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
C10orf90	“up-regulates quantity by stabilization”	TP53	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1172570	GRCh37/hg19 10q26.12-26.3(chr10:122785023-135457222)x1	Pathogenic

SpliceAI

2071 predictions. Top by Δscore:

Variant	Effect	Δscore
10:126459033:AGCTT:A	donor_loss	1.0000
10:126459034:GCTTA:G	donor_loss	1.0000
10:126459036:TTACC:T	donor_loss	1.0000
10:126459038:ACCAC:A	donor_loss	1.0000
10:126459039:C:A	donor_loss	1.0000
10:126459039:CCA:C	donor_gain	1.0000
10:126459039:CCACT:C	donor_gain	1.0000
10:126459070:T:TA	donor_gain	1.0000
10:126459214:CTTC:C	acceptor_gain	1.0000
10:126459215:TTC:T	acceptor_gain	1.0000
10:126459216:TC:T	acceptor_gain	1.0000
10:126459216:TCCT:T	acceptor_loss	1.0000
10:126459217:CC:C	acceptor_gain	1.0000
10:126459218:C:CC	acceptor_gain	1.0000
10:126459218:CTATG:C	acceptor_loss	1.0000
10:126459219:T:G	acceptor_loss	1.0000
10:126459220:A:AC	acceptor_gain	1.0000
10:126459220:A:C	acceptor_gain	1.0000
10:126425985:CATTA:C	donor_loss	0.9900
10:126425986:ATTAC:A	donor_loss	0.9900
10:126425987:TTA:T	donor_loss	0.9900
10:126425989:A:AG	donor_loss	0.9900
10:126425990:CCT:C	donor_loss	0.9900
10:126426089:TT:T	acceptor_gain	0.9900
10:126429782:AGTAC:A	donor_loss	0.9900
10:126429783:GTA:G	donor_loss	0.9900
10:126429784:TA:T	donor_loss	0.9900
10:126429785:A:AT	donor_loss	0.9900
10:126429786:CC:C	donor_loss	0.9900
10:126429786:CCT:C	donor_gain	0.9900

AlphaMissense

5235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:126459188:G:C	F583L	0.995
10:126459188:G:T	F583L	0.995
10:126459190:A:G	F583L	0.995
10:126426076:A:G	L659S	0.994
10:126425997:G:C	F685L	0.992
10:126425997:G:T	F685L	0.992
10:126425999:A:G	F685L	0.992
10:126429840:G:C	F636L	0.992
10:126429840:G:T	F636L	0.992
10:126429842:A:G	F636L	0.992
10:126459214:C:G	A575P	0.992
10:126425994:T:A	K686N	0.991
10:126425994:T:G	K686N	0.991
10:126459189:A:G	F583S	0.991
10:126425995:T:A	K686I	0.990
10:126426090:T:A	R654S	0.989
10:126426090:T:G	R654S	0.989
10:126426088:A:G	I655T	0.988
10:126429794:A:G	S652P	0.988
10:126429796:C:G	R651P	0.988
10:126459168:C:G	R590P	0.988
10:126425998:A:G	F685S	0.987
10:126429789:C:A	K653N	0.987
10:126429789:C:G	K653N	0.987
10:126429837:T:A	K637N	0.987
10:126429837:T:G	K637N	0.987
10:126429805:A:G	M648T	0.986
10:126429804:C:A	M648I	0.985
10:126429804:C:G	M648I	0.985
10:126429804:C:T	M648I	0.985

dbSNP variants (sampled 300 via entrez): RS1000007496 (10:126599518 T>C), RS1000011280 (10:126635048 G>A), RS1000026826 (10:126482220 A>G,T), RS1000031490 (10:126434823 A>C), RS1000037192 (10:126489532 C>T), RS1000038449 (10:126625110 C>T), RS1000058294 (10:126429854 GA>G,GAA), RS1000066147 (10:126630121 C>A,T), RS1000080141 (10:126482462 C>A), RS1000086641 (10:126511563 G>A,T), RS1000088717 (10:126624887 C>A), RS1000098134 (10:126630314 A>G), RS1000107674 (10:126501253 C>T), RS1000130051 (10:126441575 A>G), RS1000132154 (10:126521000 C>G,T)

Disease associations

OMIM: gene MIM:617735 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001822_13	Metabolite levels (MHPG)	2.000000e-06
GCST002794_13	Airway wall thickness	9.000000e-06
GCST002794_15	Airway wall thickness	8.000000e-08
GCST002794_3	Airway wall thickness	8.000000e-06
GCST002843_25	Sitting height ratio	2.000000e-08
GCST006609_4	Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count)	7.000000e-08
GCST006610_1	Response to TNF inhibitor in rheumatoid arthritis (change in disease activity score)	5.000000e-06
GCST008176_6	Gestational age at birth (child effect)	5.000000e-07
GCST008178_9	Early spontaneous preterm birth	2.000000e-07
GCST011663_1	Resistance to Mycobacterium tuberculosis infection	1.000000e-09
GCST011664_1	Resistance to Mycobacterium tuberculosis infection	1.000000e-07
GCST012442_20	Age-related hearing impairment	4.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005133	MHPG measurement
EFO:0006898	airway wall thickness measurement
EFO:0007118	sitting height ratio
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0009435	arthritis disease activity score measurement
EFO:0005112	gestational age
EFO:0006917	spontaneous preterm birth
EFO:0008322	decreased susceptibility to bacterial infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression	1
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	increases expression	1
aflatoxin B2	decreases methylation, increases methylation	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Ivermectin	increases expression	1
Smoke	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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