NACA

Summary

NACA (nascent polypeptide associated complex subunit alpha, HGNC:7629) is a protein-coding gene on chromosome 12q13.3, encoding Nascent polypeptide-associated complex subunit alpha, muscle-specific form (E9PAV3). Cardiac- and muscle-specific transcription factor. It is a common-essential gene (DepMap: required in 98.5% of cancer cell lines).

This gene encodes a protein that associates with basic transcription factor 3 (BTF3) to form the nascent polypeptide-associated complex (NAC). This complex binds to nascent proteins that lack a signal peptide motif as they emerge from the ribosome, blocking interaction with the signal recognition particle (SRP) and preventing mistranslocation to the endoplasmic reticulum. This protein is an IgE autoantigen in atopic dermatitis patients. Alternative splicing results in multiple transcript variants, but the full length nature of some of these variants, including those encoding very large proteins, has not been determined. There are multiple pseudogenes of this gene on different chromosomes.

Source: NCBI Gene 4666 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 209 total
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 98.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_001365896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7629
Approved symbol	NACA
Name	nascent polypeptide associated complex subunit alpha
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	NACA1, Alpha-NAC
Ensembl gene	ENSG00000196531
Ensembl biotype	protein_coding
OMIM	601234
Entrez	4666

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 34 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000356769, ENST00000393891, ENST00000454682, ENST00000546392, ENST00000546410, ENST00000546862, ENST00000547914, ENST00000548084, ENST00000548386, ENST00000548563, ENST00000549259, ENST00000549855, ENST00000550343, ENST00000550920, ENST00000550952, ENST00000551520, ENST00000551775, ENST00000551793, ENST00000552055, ENST00000552540, ENST00000676873, ENST00000678047, ENST00000678066, ENST00000678376, ENST00000678416, ENST00000679092, ENST00000901047, ENST00000901048, ENST00000901049, ENST00000921204, ENST00000921205, ENST00000921206, ENST00000921207, ENST00000921208, ENST00000921209, ENST00000921210, ENST00000921211, ENST00000921212, ENST00000921213, ENST00000921214, ENST00000951538, ENST00000951539, ENST00000951540

RefSeq mRNA: 7 — MANE Select: NM_001365896 NM_001113201, NM_001113202, NM_001113203, NM_001320193, NM_001320194, NM_001365896, NM_005594

CCDS: CCDS31837, CCDS44925, CCDS91708

Canonical transcript exons

ENST00000454682 — 9 exons

Exon	Start	End
ENSE00001647803	56715871	56721459
ENSE00002374095	56725263	56725299
ENSE00003491067	56712786	56712908
ENSE00003529588	56714362	56714439
ENSE00003607207	56714602	56714687
ENSE00003616038	56724452	56724523
ENSE00003619371	56713062	56713190
ENSE00003652317	56713537	56713683
ENSE00003896507	56712427	56712552

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 379.7688 / max 4134.8714, expressed in 1828 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131598	234.3012	1827
131599	109.4835	1825
131597	25.0682	1799
131596	6.2020	1705
131578	2.2663	1177
131600	1.3462	852
131579	1.0600	650
131580	0.0414	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.94	gold quality
mammary duct	UBERON:0001765	99.92	gold quality
upper arm skin	UBERON:0004263	99.92	gold quality
tendon	UBERON:0000043	99.91	gold quality
epithelium of nasopharynx	UBERON:0001951	99.91	gold quality
skin of hip	UBERON:0001554	99.90	gold quality
parietal pleura	UBERON:0002400	99.90	gold quality
calcaneal tendon	UBERON:0003701	99.90	gold quality
germinal epithelium of ovary	UBERON:0001304	99.89	gold quality
epithelium of mammary gland	UBERON:0003244	99.89	gold quality
upper leg skin	UBERON:0004262	99.89	gold quality
caput epididymis	UBERON:0004358	99.88	gold quality
cortical plate	UBERON:0005343	99.88	gold quality
cartilage tissue	UBERON:0002418	99.87	gold quality
corpus epididymis	UBERON:0004359	99.87	gold quality
thoracic mammary gland	UBERON:0005200	99.87	gold quality
mammalian vulva	UBERON:0000997	99.86	gold quality
superficial temporal artery	UBERON:0001614	99.86	gold quality
mammary gland	UBERON:0001911	99.86	gold quality
medial globus pallidus	UBERON:0002477	99.86	gold quality
palpebral conjunctiva	UBERON:0001812	99.85	gold quality
cerebellar cortex	UBERON:0002129	99.85	gold quality
cerebellar hemisphere	UBERON:0002245	99.85	gold quality
ganglionic eminence	UBERON:0004023	99.85	gold quality
mucosa of urinary bladder	UBERON:0001259	99.84	gold quality
pigmented layer of retina	UBERON:0001782	99.84	gold quality
gingival epithelium	UBERON:0001949	99.84	gold quality
cauda epididymis	UBERON:0004360	99.84	gold quality
cerebellar vermis	UBERON:0004720	99.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.84	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	2373.28
E-CURD-122	yes	98.23
E-CURD-88	yes	60.14
E-MTAB-10042	yes	15.38
E-HCAD-9	yes	12.76
E-MTAB-9801	yes	5.70
E-CURD-95	no	2701.70
E-CURD-53	no	971.36
E-GEOD-75140	no	790.46
E-MTAB-7037	no	529.32
E-HCAD-4	no	142.83
E-CURD-46	no	41.79
E-HCAD-1	no	22.21
E-GEOD-125970	no	21.42
E-HCAD-31	no	20.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

4 targeting NACA, 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-101-3P	99.94	75.03	2230
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-495-5P	97.62	68.28	682

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer’ s disease and Down syndrome. (PMID:12109594)
• a novel isoform of alpha-nascent polypeptide-associated complex as IgE-defined autoantigen (PMID:12406326)
• virtual Northern blots to analyze expression of NACA and ANX2 in progenitor cultures of nine children with Juvenile myelomonocytic leukemia and five healthy individuals (PMID:12699894)
• Altogether, these results characterize NACA as a new factor involved in the positive regulation of human erythroid-cell differentiation. (PMID:15784678)
• Alpha NAC downregulation in hypoxic cells or NAC ablation by NAC short-interfering RNA (siRNA) leads to the initiation of ER stress responses, which results in caspase-dependent apoptosis. (PMID:19609276)
• identified a region in the NAC domain of the human NAC alpha-subunit as a new nucleic acid-binding region, which is blocked from binding nucleic acids in the heterodimeric complex by a helix region in the beta-subunit (PMID:20214399)
• NACA gene expression is decreased in both classic and follicular variants of papillary thyroid carcinoma. (PMID:21509594)
• [review] First evidence of a functional interaction between ATF4, FIAT (factor-inhibiting ATF4-mediated transcription) and alphaNAC (nascent polypeptide-associated complex and coactivator alpha). (PMID:22082360)
• depletion of alphaNAC in multiple types of cancer cells induce typical apoptotic cell death. This anti-apoptotic function is mediated by the FADD/c-Jun N-terminal kinase pathway. (PMID:24901053)
• Low NACA expression is associated with rhabdomyosarcoma. (PMID:25209525)
• These results suggest that PP1A dephosphorylates NACA at specific residues, impacting cJUN transcriptional activity and osteoblast differentiation and function. (PMID:30948508)
• NAC is a potent suppressor of aggregation and proteotoxicity of mutant PolyQ-expanded proteins associated with human diseases like Huntington’s disease and spinocerebellar ataxias. (PMID:30982745)
• The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF-alpha. (PMID:36219563)
• A 220 kDa isoform of Naca is expressed in mouse muscle tissues (PMID:8698236)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	naca	ENSDARG00000005513
mus_musculus	Naca	ENSMUSG00000061315
rattus_norvegicus	Naca	ENSRNOG00000002632
caenorhabditis_elegans	icd-2	WBGENE00022042

Paralogs (2): NACAD (ENSG00000136274), NACA2 (ENSG00000253506)

Protein

Protein identifiers

Nascent polypeptide-associated complex subunit alpha, muscle-specific form — E9PAV3 (reviewed: E9PAV3, Q13765)

Alternative names: Alpha-NAC, muscle-specific form

All UniProt accessions (11): E9PAV3, Q13765, A0A7I2V2K5, A0A7I2V473, F8VNW4, F8VZ58, F8VZJ2, F8W029, F8W0C7, F8W0W4, H0YHX9

UniProt curated annotations — full annotation on UniProt →

Function. Cardiac- and muscle-specific transcription factor. May act to regulate the expression of genes involved in the development of myotubes. Plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. Involved in the organized assembly of thick and thin filaments of myofibril sarcomeres.

Subunit / interactions. Interacts (via PXLXP motif) with the muscle-restricted histone methyltransferase SMYD1 (via MYND-type zinc finger).

Subcellular location. Cytoplasm. Nucleus.

Domain organisation. The proline-rich muscle-specific exon 3 contains eighteen approximate 23-AA repeats.

Isoforms (3)

UniProt ID	Names	Canonical?
E9PAV3-1	skNAC	yes
Q13765-1	1
E9PAV3-2	skNAC-2, 2

RefSeq proteins (7): NP_001106672, NP_001106673, NP_001106674, NP_001307122, NP_001307123, NP_001352825, NP_005585 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002715	Nas_poly-pep-assoc_cplx_dom	Domain
IPR016641	EGD2/NACA0like	Family
IPR038187	NAC_A/B_dom_sf	Homologous_superfamily
IPR044034	NAC-like_UBA	Domain

Pfam: PF01849, PF19026

UniProt features (83 total): compositionally biased region 29, modified residue 22, region of interest 8, sequence variant 5, strand 5, domain 4, chain 2, cross-link 2, splice variant 2, sequence conflict 2, short sequence motif 1, helix 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
3MCB	X-RAY DIFFRACTION	1.9
9I2D	ELECTRON MICROSCOPY	2.19
9S3D	ELECTRON MICROSCOPY	2.32
9S3B	ELECTRON MICROSCOPY	2.38
3MCE	X-RAY DIFFRACTION	2.4
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
3LKX	X-RAY DIFFRACTION	2.5
9QLQ	ELECTRON MICROSCOPY	2.57
9MR4	ELECTRON MICROSCOPY	2.65
9QLP	ELECTRON MICROSCOPY	2.75
9QQA	ELECTRON MICROSCOPY	2.8
9NDP	ELECTRON MICROSCOPY	2.82
7QWQ	ELECTRON MICROSCOPY	2.83
7QWR	ELECTRON MICROSCOPY	2.9
8P2K	ELECTRON MICROSCOPY	2.9
9I2E	ELECTRON MICROSCOPY	2.95
9F1B	ELECTRON MICROSCOPY	3.01
9F1D	ELECTRON MICROSCOPY	3.26
7QWS	ELECTRON MICROSCOPY	3.4
9QQB	ELECTRON MICROSCOPY	3.43
9SYR	ELECTRON MICROSCOPY	3.55
9F1C	ELECTRON MICROSCOPY	3.78
9FQ0	ELECTRON MICROSCOPY	4.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-E9PAV3-F1	38.15	0.05
AF-Q13765-F1	73.06	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

E9PAV3 (canonical)

Post-translational modifications (14): 917, 1181, 1397, 1474, 1906, 1995, 2005, 2022, 2024, 2029, 2049, 2054, 2066, 2005

Q13765

Post-translational modifications (10): 132, 142, 159, 161, 166, 186, 191, 203, 142, 43

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 290 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_HEART_TRABECULA_MORPHOGENESIS, GNF2_BNIP2, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, MODULE_151, LFA1_Q6, GCM_NPM1, MORF_SNRP70, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I

GO Biological Process (14): protein targeting to membrane (GO:0006612), negative regulation of transcription by RNA polymerase II (GO:0000122), cardiac ventricle development (GO:0003231), translation (GO:0006412), negative regulation of striated muscle cell apoptotic process (GO:0010664), protein transport (GO:0015031), wound healing (GO:0042060), skeletal muscle tissue regeneration (GO:0043403), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of skeletal muscle tissue growth (GO:0048633), regulation of skeletal muscle fiber development (GO:0048742), heart trabecula morphogenesis (GO:0061384), negative regulation of protein localization to endoplasmic reticulum (GO:1905551), positive regulation of cell proliferation involved in heart morphogenesis (GO:2000138)

GO Molecular Function (4): DNA binding (GO:0003677), obsolete unfolded protein binding (GO:0051082), transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), nascent polypeptide-associated complex (GO:0005854), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
tissue regeneration	2
positive regulation of DNA-templated transcription	2
protein targeting	1
establishment of protein localization to membrane	1
negative regulation of DNA-templated transcription	1
cardiac chamber development	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
negative regulation of muscle cell apoptotic process	1
striated muscle cell apoptotic process	1
regulation of striated muscle cell apoptotic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
response to wounding	1
skeletal muscle tissue growth	1
regulation of skeletal muscle tissue growth	1
positive regulation of developmental growth	1
positive regulation of skeletal muscle tissue development	1
regulation of myotube differentiation	1
skeletal muscle fiber development	1
regulation of cell development	1
trabecula morphogenesis	1
protein localization to endoplasmic reticulum	1
negative regulation of protein localization	1
regulation of protein localization to endoplasmic reticulum	1
positive regulation of cell population proliferation	1
cell proliferation involved in heart morphogenesis	1
regulation of cell proliferation involved in heart morphogenesis	1
nucleic acid binding	1
transcription coregulator activity	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
DNM1L	NACA	psi-mi:“MI:0915”(physical association)	0.400
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
MAB21L2	PTBP1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ATG13	ENAH	psi-mi:“MI:0914”(association)	0.350
CSNK2A1	RPS3A	psi-mi:“MI:0914”(association)	0.350
PDZD8	ENAH	psi-mi:“MI:0914”(association)	0.350
SLC24A5	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC28A2	NACA	psi-mi:“MI:0914”(association)	0.350
CTNNA1	MYO1G	psi-mi:“MI:0914”(association)	0.350
CASP3	NACA	psi-mi:“MI:0914”(association)	0.350
STAT3	NACA	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
DCTN1	NACA	psi-mi:“MI:2364”(proximity)	0.270
CANX	NACA	psi-mi:“MI:2364”(proximity)	0.270
KCNJ2	ELAPOR2	psi-mi:“MI:2364”(proximity)	0.270
SWSAP1	NACA	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
EFTUD2	NACA	psi-mi:“MI:2364”(proximity)	0.270
GNL3	VWA8	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ILF3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (333): BTF3 (Reconstituted Complex), NACA (Affinity Capture-MS), NACA (Two-hybrid), NACA (Affinity Capture-MS), NACA (Affinity Capture-Western), NACA (Affinity Capture-MS), EEF1G (Co-fractionation), NACA (Co-fractionation), NACA (Co-fractionation), NACA (Co-fractionation), NACA (Co-fractionation), NACA (Co-fractionation), NACA (Co-fractionation), NACA (Affinity Capture-MS), NACA (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

Diamond homologs: A1CMF8, A1DLM0, A2R4V1, A3GHD3, A4RC89, A5DGN9, A5DXK7, A6R641, A6SB28, A6ZT99, A7EIZ1, A7TG43, E9PAV3, O15069, P0C2C7, P0CP06, P0CP07, P38879, P70670, P87147, Q0UKB5, Q13765, Q1DHR3, Q2H4Z2, Q2U955, Q45FF9, Q4I2J8, Q4P341, Q4WD81, Q5ANP2, Q5AYK0, Q5E9A1, Q5R9I9, Q5SWP3, Q60817, Q61UX1, Q68F90, Q6BSN9, Q6CDH0, Q6CWG6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GSK3B	down-regulates	NACA	phosphorylation
ILK	up-regulates	NACA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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
SARS-CoV-1-host interactions	6	24.5×	6e-05
SARS-CoV-1 Infection	6	19.9×	1e-04
Formation of a pool of free 40S subunits	5	13.0×	3e-03
L13a-mediated translational silencing of Ceruloplasmin expression	5	11.8×	3e-03
GTP hydrolysis and joining of the 60S ribosomal subunit	5	11.7×	3e-03
SARS-CoV-2 Infection	5	9.3×	5e-03
mRNA Splicing - Major Pathway	7	8.9×	1e-03
Major pathway of rRNA processing in the nucleolus and cytosol	6	8.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	16.2×	9e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — BCC, BLCA, MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	28
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

819 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56712779:CACTT:C	donor_loss	1.0000
12:56712780:ACTTA:A	donor_loss	1.0000
12:56712781:CTTA:C	donor_loss	1.0000
12:56712782:TTA:T	donor_loss	1.0000
12:56712783:T:TG	donor_loss	1.0000
12:56712784:A:AC	donor_gain	1.0000
12:56712785:C:CG	donor_gain	1.0000
12:56712785:CCAT:C	donor_gain	1.0000
12:56712785:CCATA:C	donor_gain	1.0000
12:56712904:TCGAC:T	acceptor_gain	1.0000
12:56712905:CGAC:C	acceptor_gain	1.0000
12:56712905:CGACC:C	acceptor_gain	1.0000
12:56712906:GAC:G	acceptor_gain	1.0000
12:56712907:AC:A	acceptor_gain	1.0000
12:56712908:CC:C	acceptor_gain	1.0000
12:56712909:C:CA	acceptor_loss	1.0000
12:56712909:C:CC	acceptor_gain	1.0000
12:56712909:C:T	acceptor_gain	1.0000
12:56712916:A:AC	acceptor_gain	1.0000
12:56712916:A:C	acceptor_gain	1.0000
12:56713051:T:A	donor_gain	1.0000
12:56713059:TA:T	donor_loss	1.0000
12:56713060:A:AG	donor_loss	1.0000
12:56713061:C:CT	donor_loss	1.0000
12:56713061:CCT:C	donor_gain	1.0000
12:56713063:T:TA	donor_gain	1.0000
12:56713066:T:TA	donor_gain	1.0000
12:56713078:T:A	donor_gain	1.0000
12:56713186:TCGAT:T	acceptor_gain	1.0000
12:56713187:CGAT:C	acceptor_gain	1.0000

AlphaMissense

12951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56712790:A:C	I2073S	1.000
12:56712790:A:T	I2073N	1.000
12:56712794:C:G	A2072P	1.000
12:56712823:A:G	L2062P	1.000
12:56712827:C:G	A2061P	1.000
12:56712832:A:T	V2059D	1.000
12:56712836:C:G	A2058P	1.000
12:56712868:A:T	V2047D	1.000
12:56713162:A:G	L2000P	1.000
12:56713184:C:G	D1993H	1.000
12:56713547:C:A	G1987V	1.000
12:56713547:C:T	G1987E	1.000
12:56713548:C:A	G1987W	1.000
12:56713548:C:G	G1987R	1.000
12:56713548:C:T	G1987R	1.000
12:56713549:A:C	F1986L	1.000
12:56713549:A:T	F1986L	1.000
12:56713551:A:G	F1986L	1.000
12:56713553:A:T	V1985D	1.000
12:56713556:A:C	I1984R	1.000
12:56713556:A:T	I1984K	1.000
12:56713560:A:C	Y1983D	1.000
12:56713579:C:A	K1976N	1.000
12:56713579:C:G	K1976N	1.000
12:56713584:A:C	Y1975D	1.000
12:56713586:A:T	V1974D	1.000
12:56713601:A:T	I1969N	1.000
12:56713604:A:T	V1968D	1.000
12:56713606:A:C	F1967L	1.000
12:56713606:A:T	F1967L	1.000

dbSNP variants (sampled 300 via entrez): RS1000338432 (12:56724601 A>G), RS1000345190 (12:56717552 G>A,T), RS1000541241 (12:56720014 A>T), RS1000587627 (12:56712453 CTTTA>C), RS1000881188 (12:56725359 G>A), RS1000913723 (12:56725539 C>T), RS1001192430 (12:56719305 G>A), RS1001272189 (12:56719128 A>C), RS1001407851 (12:56725050 T>G), RS1001426321 (12:56725193 C>T), RS1001455711 (12:56725305 G>A,C), RS1002075686 (12:56712959 G>A), RS1002916522 (12:56720512 A>C), RS1003250409 (12:56722069 GT>G), RS1003750304 (12:56716071 G>A,C)

Disease associations

OMIM: gene MIM:601234 | 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
GCST006061_174	Atrial fibrillation	1.000000e-09
GCST006061_189	Atrial fibrillation	6.000000e-12
GCST006414_11	Atrial fibrillation	1.000000e-12
GCST006414_63	Atrial fibrillation	2.000000e-08
GCST006630_35	Diastolic blood pressure	4.000000e-17
GCST007103_18	QRS duration	6.000000e-10
GCST007104_12	QRS duration	4.000000e-15
GCST008916_110	Asthma	1.000000e-27
GCST008916_18	Asthma	8.000000e-18
GCST010918_4	JT interval	6.000000e-08
GCST90013663_71	Alanine aminotransferase levels	2.000000e-11
GCST90013664_101	Aspartate aminotransferase levels	9.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0007885	JT interval
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Formaldehyde	decreases expression	2
Valproic Acid	decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	decreases reaction, affects expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
cupric oxide	increases expression	1
quinoline	decreases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
bromovanin	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3BS	Abcam HEK293T NACA KO	Transformed cell line	Female

Clinical trials (associated diseases)

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