CUTA

Summary

CUTA (cutA divalent cation tolerance homolog, HGNC:21101) is a protein-coding gene on chromosome 6p21.32, encoding Protein CutA (O60888). May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE).

Enables enzyme binding activity. Involved in protein localization. Located in membrane and mitochondrion.

Source: NCBI Gene 51596 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 46 total
• Druggable target: yes
• MANE Select transcript: NM_001014840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21101
Approved symbol	CUTA
Name	cutA divalent cation tolerance homolog
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112514
Ensembl biotype	protein_coding
OMIM	616953
Entrez	51596

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000374484, ENST00000374496, ENST00000374500, ENST00000440279, ENST00000462802, ENST00000465956, ENST00000479249, ENST00000482684, ENST00000487637, ENST00000488034, ENST00000488478, ENST00000492510, ENST00000494751, ENST00000607266, ENST00000879000

RefSeq mRNA: 5 — MANE Select: NM_001014840 NM_001014433, NM_001014837, NM_001014838, NM_001014840, NM_015921

CCDS: CCDS34433, CCDS4779

Canonical transcript exons

ENST00000440930 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 207.7535 / max 754.7523, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73161	84.1255	1825
73164	51.9452	1824
73165	41.8743	1818
73162	21.1667	1781
73163	7.2983	1734
73159	0.9390	522
73160	0.4045	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	99.40	gold quality
adenohypophysis	UBERON:0002196	99.40	gold quality
right adrenal gland cortex	UBERON:0035827	99.09	gold quality
right adrenal gland	UBERON:0001233	99.08	gold quality
left adrenal gland	UBERON:0001234	99.08	gold quality
left adrenal gland cortex	UBERON:0035825	99.08	gold quality
putamen	UBERON:0001874	98.93	gold quality
left lobe of thyroid gland	UBERON:0001120	98.90	gold quality
nucleus accumbens	UBERON:0001882	98.90	gold quality
right lobe of thyroid gland	UBERON:0001119	98.89	gold quality
caudate nucleus	UBERON:0001873	98.84	gold quality
stromal cell of endometrium	CL:0002255	98.81	gold quality
thyroid gland	UBERON:0002046	98.78	gold quality
right uterine tube	UBERON:0001302	98.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.73	gold quality
fundus of stomach	UBERON:0001160	98.71	gold quality
prefrontal cortex	UBERON:0000451	98.70	gold quality
endocervix	UBERON:0000458	98.70	gold quality
hypothalamus	UBERON:0001898	98.70	gold quality
primary visual cortex	UBERON:0002436	98.70	gold quality
substantia nigra	UBERON:0002038	98.67	gold quality
left ovary	UBERON:0002119	98.67	gold quality
right frontal lobe	UBERON:0002810	98.67	gold quality
brain	UBERON:0000955	98.64	gold quality
cortex of kidney	UBERON:0001225	98.64	gold quality
body of stomach	UBERON:0001161	98.63	gold quality
Ammon’s horn	UBERON:0001954	98.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.63	gold quality
frontal cortex	UBERON:0001870	98.62	gold quality
amygdala	UBERON:0001876	98.62	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	562.88
E-GEOD-81547	no	10.56
E-HCAD-31	no	2.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting CUTA, 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-186-3P	99.51	66.24	1685
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-483-5P	93.53	65.81	111

Literature-anchored findings (GeneRIF, showing 6)

• Fluorescence in situ hybridization localizes the gene to chromosome 6p21.32-p21.2. (PMID:10800960)
• expression profile of CUTA gene in tissues was examined & revealed CUTA gene was constitutively expressed in the 18 tissues tested; CUTA isoform2 was mainly located in mitochondria as a new potential mitochondrial protein (PMID:17924204)
• H component of CUTA as a novel BACE1-interacting protein that mediates the intracellular trafficking of BACE1 and the processing of APP to Abeta (PMID:22351782)
• Human CutA1 exhibits remarkably high thermodynamic stability at body temperature should be important for its protein catabolism in the human cells. (PMID:25344844)
• It mediates APP processing and Abeta generation. (PMID:25557959)
• Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease. (PMID:37962983)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cuta	ENSMUSG00000024194
rattus_norvegicus	Cuta	ENSRNOG00000000481
drosophila_melanogaster	CG11590	FBGN0030545
caenorhabditis_elegans		WBGENE00009443

Protein

Protein identifiers

Protein CutA — O60888 (reviewed: O60888)

Alternative names: Acetylcholinesterase-associated protein, Brain acetylcholinesterase putative membrane anchor

All UniProt accessions (5): O60888, C9IZG4, C9IZQ5, F2Z2Q5, H0YDR4

UniProt curated annotations — full annotation on UniProt →

Function. May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE).

Subunit / interactions. Homotrimer.

Tissue specificity. Ubiquitous. Widely expressed in brain.

Post-translational modifications. O-glycosylated.

Similarity. Belongs to the CutA family.

Isoforms (3)

UniProt ID	Names	Canonical?
O60888-1	B	yes
O60888-2	A
O60888-3	C

RefSeq proteins (5): NP_001014433, NP_001014837, NP_001014838, NP_001014840, NP_057005 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004323	Ion_tolerance_CutA	Family
IPR011322	N-reg_PII-like_a/b	Homologous_superfamily
IPR015867	N-reg_PII/ATP_PRibTrfase_C	Homologous_superfamily

Pfam: PF03091

UniProt features (14 total): strand 5, helix 4, splice variant 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2ZFH	X-RAY DIFFRACTION	2.05
1XK8	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60888-F1	80.16	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): CGGAARNGGCNG_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, AACWWCAANK_UNKNOWN, COUP_01, GOBP_RESPONSE_TO_METAL_ION, PATIL_LIVER_CANCER, TCF4_Q5, ATF1_Q6, USF_01, TCF11_01, HNF4_DR1_Q3, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, HNF4_01

GO Biological Process (2): intracellular protein localization (GO:0008104), response to metal ion (GO:0010038)

GO Molecular Function (3): copper ion binding (GO:0005507), enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), membrane (GO:0016020), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	1
response to chemical	1
transition metal ion binding	1
protein binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

971 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUTA	CUTC	Q9NTM9	736
CUTA	HSPE1	P61604	727
CUTA	SYNGAP1	Q96PV0	578
CUTA	TAX1BP3	O14907	547
CUTA	BACE1	P56817	507
CUTA	HSPD1	P10809	474
CUTA	PHF1	O43189	474
CUTA	WASHC4	Q2M389	435
CUTA	GABRB1	P18505	410
CUTA	UBAC1	Q9BSL1	410
CUTA	WDR46	O15213	405
CUTA	PFDN6	O15212	373
CUTA	APEH	P13798	368
CUTA	A0A1W2PPA2	A0A1W2PPA2	368
CUTA	NXN	Q6DKJ4	365

IntAct

22 interactions, top by confidence:

A	B	Type	Score
FBLIM1	CUTA	psi-mi:“MI:0915”(physical association)	0.740
CUTA	FBLIM1	psi-mi:“MI:0915”(physical association)	0.740
CUTA	PRKAG1	psi-mi:“MI:0914”(association)	0.530
NR4A1	CUTA	psi-mi:“MI:0915”(physical association)	0.520
CPLX3	CUTA	psi-mi:“MI:0915”(physical association)	0.400
CUTA	MLH1	psi-mi:“MI:0915”(physical association)	0.370
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
CUTA	UBB	psi-mi:“MI:0914”(association)	0.350
FBLIM1	ILVBL	psi-mi:“MI:0914”(association)	0.350
CUTA	ERI3	psi-mi:“MI:0914”(association)	0.350
VHL	CUTA	psi-mi:“MI:0915”(physical association)	0.000
PINX1	CUTA	psi-mi:“MI:0915”(physical association)	0.000
MCC	CUTA	psi-mi:“MI:0915”(physical association)	0.000
GRB2	CUTA	psi-mi:“MI:0915”(physical association)	0.000
CUTA	NR4A1	psi-mi:“MI:0915”(physical association)	0.000
tolC	CUTA	psi-mi:“MI:0915”(physical association)	0.000
	CUTA	psi-mi:“MI:0915”(physical association)	0.000
CUTA	map	psi-mi:“MI:0915”(physical association)	0.000
aguA	CUTA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (65): FBLIM1 (Two-hybrid), CUTA (Co-fractionation), PXDNL (Co-fractionation), CUTA (Affinity Capture-MS), CUTA (Affinity Capture-MS), UPP1 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), UBB (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), GID4 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), PRKAG1 (Affinity Capture-MS), PDIA5 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A4D126, D2GU20, E1BCH6, E9PYK3, O35465, O60888, O75425, O75808, P43896, P47823, P69678, P97812, Q0VC80, Q13144, Q14318, Q27J81, Q2VPK5, Q3B7U9, Q3TX08, Q3U269, Q496Y0, Q499R4, Q5ND52, Q5RJG7, Q5S6T3, Q64350, Q66KY3, Q6MGD0, Q6ZT62, Q7T0X7, Q7T3C3, Q86U90, Q8BGG6, Q8BYH7, Q8CHW4, Q8HXH0, Q8IYL2, Q91YR5, Q96EN8

Diamond homologs: A4TRR5, A7FN06, A7ZV06, A8A7N3, A8AMR3, A9QYQ6, B1ITR1, B1JMR6, B1LQF8, B1XD17, B2K1X9, B2TY12, B4T2N5, B4TF74, B4TSC0, B5BKE7, B5F2K4, B5FRJ6, B5QZZ9, B5R985, B5Z2E7, B6I609, B7LBZ6, B7M8P8, B7MKU2, B7MSF8, B7NG75, B7NTJ6, C5A1C9, O28301, O58720, O60888, P69488, P69489, P69678, P93009, Q0SXE2, Q0T9Q4, Q109R6, Q1C0X5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

874 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33416772:CAGAA:C	acceptor_gain	1.0000
6:33417249:A:AC	donor_gain	1.0000
6:33417250:C:CC	donor_gain	1.0000
6:33417250:CATGG:C	donor_gain	1.0000
6:33416773:AGAA:A	acceptor_gain	0.9900
6:33416774:GAA:G	acceptor_gain	0.9900
6:33416777:C:CC	acceptor_gain	0.9900
6:33417091:TCTCA:T	donor_loss	0.9900
6:33417093:TCA:T	donor_loss	0.9900
6:33417096:C:CT	donor_loss	0.9900
6:33417138:CATAG:C	acceptor_gain	0.9900
6:33417140:TAG:T	acceptor_gain	0.9900
6:33417143:C:CA	acceptor_loss	0.9900
6:33417143:C:CC	acceptor_gain	0.9900
6:33417244:GAC:G	donor_loss	0.9900
6:33417245:ACT:A	donor_loss	0.9900
6:33417246:CT:C	donor_loss	0.9900
6:33417247:TCAC:T	donor_loss	0.9900
6:33417248:CACAT:C	donor_loss	0.9900
6:33417249:A:AG	donor_loss	0.9900
6:33417250:C:T	donor_loss	0.9900
6:33417250:CA:C	donor_gain	0.9900
6:33417250:CATG:C	donor_gain	0.9900
6:33417306:CGGCC:C	acceptor_gain	0.9900
6:33417670:C:CT	acceptor_gain	0.9900
6:33417670:C:T	acceptor_gain	0.9900
6:33417671:A:T	acceptor_gain	0.9900
6:33416775:AACTA:A	acceptor_loss	0.9800
6:33416777:C:T	acceptor_loss	0.9800
6:33416778:T:A	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001093191 (6:33419095 G>C), RS1002716361 (6:33418485 G>T), RS1004492886 (6:33416085 G>A), RS1004624786 (6:33420017 C>CTCG), RS1006019701 (6:33418392 G>T), RS1007878051 (6:33417692 A>G), RS1009250484 (6:33418436 G>T), RS1010489520 (6:33417317 T>A), RS1010586011 (6:33418622 C>T), RS1010700519 (6:33418304 C>T), RS1011571867 (6:33416156 C>G,T), RS1011624341 (6:33416416 T>C), RS1012316140 (6:33417766 C>G,T), RS1013339851 (6:33419658 T>C,G), RS1013582120 (6:33416163 C>T)

Disease associations

OMIM: gene MIM:616953 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004521_251	Autism spectrum disorder or schizophrenia	6.000000e-12
GCST004521_287	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004521_75	Autism spectrum disorder or schizophrenia	8.000000e-10
GCST005951_153	Body mass index	5.000000e-09
GCST007656_5	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067022 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	4
(+)-JQ1 compound	decreases expression	3
Arsenic	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
ICG 001	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Aminoglutethimide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	affects expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Zearalenone	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Genistein	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651226	Binding	Binding affinity to human CUTA incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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