DIPK2A

Summary

DIPK2A (divergent protein kinase domain 2A, HGNC:28490) is a protein-coding gene on chromosome 3q24, encoding Divergent protein kinase domain 2A (Q8NDZ4). May play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PPI3K-AKT-CDK7 signaling cascade.

Involved in several processes, including cardiac muscle cell proliferation; negative regulation of smooth muscle cell apoptotic process; and positive regulation of protein kinase C activity. Located in Golgi membrane and extracellular space. Part of COPI vesicle coat.

Source: NCBI Gene 205428 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_173552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28490
Approved symbol	DIPK2A
Name	divergent protein kinase domain 2A
Location	3q24
Locus type	gene with protein product
Status	Approved
Aliases	MGC33365, DIA1, HASF
Ensembl gene	ENSG00000181744
Ensembl biotype	protein_coding
OMIM	612200
Entrez	205428

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000315691, ENST00000441925, ENST00000483808, ENST00000491798, ENST00000492452, ENST00000493396, ENST00000495414

RefSeq mRNA: 3 — MANE Select: NM_173552 NM_001134470, NM_001363944, NM_173552

CCDS: CCDS3130, CCDS46929, CCDS87151

Canonical transcript exons

ENST00000315691 — 3 exons

Exon	Start	End
ENSE00001215758	143971823	143972989
ENSE00001944784	143989510	143992368
ENSE00003657390	143985543	143985846

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7019 / max 315.7795, expressed in 1755 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38987	2.8572	1250
38993	2.2154	1001
38988	2.1256	1079
38989	2.0969	1155
38990	0.6696	420
38986	0.5700	215
38991	0.1254	48
38992	0.0417	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	97.61	gold quality
tibia	UBERON:0000979	97.14	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.14	gold quality
upper arm skin	UBERON:0004263	97.08	gold quality
upper leg skin	UBERON:0004262	96.64	gold quality
endothelial cell	CL:0000115	96.20	gold quality
corpus callosum	UBERON:0002336	95.86	gold quality
adrenal tissue	UBERON:0018303	95.50	gold quality
skin of hip	UBERON:0001554	95.30	gold quality
esophagus squamous epithelium	UBERON:0006920	94.69	gold quality
germinal epithelium of ovary	UBERON:0001304	94.65	gold quality
penis	UBERON:0000989	94.59	gold quality
parietal pleura	UBERON:0002400	94.31	gold quality
epithelium of nasopharynx	UBERON:0001951	94.03	gold quality
oral cavity	UBERON:0000167	93.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.55	gold quality
thymus	UBERON:0002370	93.39	gold quality
urethra	UBERON:0000057	93.32	gold quality
placenta	UBERON:0001987	93.24	gold quality
inferior vagus X ganglion	UBERON:0005363	92.97	gold quality
saphenous vein	UBERON:0007318	92.94	gold quality
lower lobe of lung	UBERON:0008949	92.70	gold quality
seminal vesicle	UBERON:0000998	92.61	gold quality
layer of synovial tissue	UBERON:0007616	92.41	gold quality
trabecular bone tissue	UBERON:0002483	92.35	gold quality
epithelium of mammary gland	UBERON:0003244	92.31	gold quality
mammary duct	UBERON:0001765	92.30	gold quality
visceral pleura	UBERON:0002401	92.28	gold quality
ventricular zone	UBERON:0003053	92.25	gold quality
mammalian vulva	UBERON:0000997	92.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	404.77
E-MTAB-6701	yes	53.74
E-HCAD-13	yes	22.71
E-ANND-3	yes	11.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting DIPK2A, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 3)

• results support a model where the DIA1 and DIA1R regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation (PMID:21264219)
• HASF (C3orf58) is a novel ligand of IGF1R. (PMID:28096202)
• DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B. (PMID:31251111)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dipk2aa	ENSDARG00000012816
danio_rerio	dipk2ab	ENSDARG00000055629
mus_musculus	Dipk2a	ENSMUSG00000045414
rattus_norvegicus	Dipk2a	ENSRNOG00000008519
drosophila_melanogaster	CG11170	FBGN0034705

Paralogs (1): DIPK2B (ENSG00000147113)

Protein

Protein identifiers

Divergent protein kinase domain 2A — Q8NDZ4 (reviewed: Q8NDZ4)

Alternative names: Deleted in autism protein 1, Golgi Protein of 49 kDa, Hypoxia and AKT-induced stem cell factor

All UniProt accessions (3): Q8NDZ4, C9JY09, E7ET39

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PPI3K-AKT-CDK7 signaling cascade.

Subcellular location. Cytoplasmic vesicle. COPI-coated vesicle. Golgi apparatus. Secreted.

Disease relevance. Genetic variations in C3orf58 may be associated with susceptibility to autism.

Similarity. Belongs to the DIPK family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDZ4-1	1	yes
Q8NDZ4-2	2

RefSeq proteins (3): NP_001127942, NP_001350873, NP_775823* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020519	DIPK2A/B	Family
IPR022049	FAM69_kinase_dom	Domain

Pfam: PF12260

UniProt features (4 total): splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDZ4-F1	89.36	0.73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): RRAGTTGT_UNKNOWN, chr3q24, AAGCAAT_MIR137, GOBP_MUSCLE_TISSUE_DEVELOPMENT, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_GROWTH, TATTATA_MIR374, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_MUSCLE_CELL_PROLIFERATION, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, AAACCAC_MIR140

GO Biological Process (4): negative regulation of smooth muscle cell apoptotic process (GO:0034392), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), cardiac muscle cell proliferation (GO:0060038), positive regulation of protein kinase C activity (GO:1900020)

GO Molecular Function (0):

GO Cellular Component (7): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), COPI vesicle coat (GO:0030126), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), COPI-coated vesicle (GO:0030137), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Golgi apparatus	2
cytoplasm	2
negative regulation of muscle cell apoptotic process	1
smooth muscle cell apoptotic process	1
regulation of smooth muscle cell apoptotic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
diacylglycerol-dependent serine/threonine kinase activity	1
positive regulation of protein serine/threonine kinase activity	1
regulation of protein kinase C activity	1
bounding membrane of organelle	1
vesicle coat	1
COPI-coated vesicle membrane	1
cellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi-associated vesicle	1
coated vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIPK2A	SLC9A9	Q8IVB4	853
DIPK2A	PCDH10	Q9P2E7	840
DIPK2A	SLC9A6	Q92581	826
DIPK2A	NPAS4	Q8IUM7	817
DIPK2A	PCDH18	Q9HCL0	762
DIPK2A	PCDH8	O95206	715
DIPK2A	SLC9A1	P19634	663
DIPK2A	SLC9A7	Q96T83	633
DIPK2A	DIPK1A	Q5T7M9	570
DIPK2A	PCDH11X	Q9BZA7	518
DIPK2A	SLC9A8	Q9Y2E8	497
DIPK2A	DOCK3	Q8IZD9	492
DIPK2A	NXF3	Q9H4D5	461
DIPK2A	GIGYF2	Q6Y7W6	453
DIPK2A	ENOX2	Q16206	440

IntAct

63 interactions, top by confidence:

A	B	Type	Score
DIPK2A	GOLPH3L	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
BIRC2	UMAD1	psi-mi:“MI:0914”(association)	0.350
TNFAIP3	KIF5C	psi-mi:“MI:0914”(association)	0.350
DIPK2A	GFAP	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
M	LTN1	psi-mi:“MI:0914”(association)	0.350
DIPK2A	C11orf98	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
GORASP2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHRNA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
COMTD1	TARS3	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (93): RNF123 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), GOLPH3L (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), GOLPH3L (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), GFAP (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), C3orf58 (Affinity Capture-MS), C3orf58 (Proximity Label-MS), C3orf58 (Proximity Label-MS)

ESM2 similar proteins: A0JPE1, B1H2T2, D3ZEH5, O18756, O77783, O94923, O95461, P70428, Q2TBU2, Q3TUA9, Q3USZ8, Q4R5B4, Q4V8A9, Q58CX7, Q5NDE9, Q5R634, Q5R903, Q5RAQ5, Q5REF6, Q5RF53, Q5T7M9, Q5XIK2, Q66PG3, Q6GMK0, Q6ZQ11, Q86X52, Q8BFR2, Q8BHY8, Q8BJQ9, Q8C3I9, Q8CIF6, Q8IWV8, Q8N475, Q8NBJ9, Q8NDZ4, Q8TDX6, Q91W96, Q93063, Q95JJ0, Q96F81

Diamond homologs: B1H2T2, Q3USZ8, Q58CX7, Q8C3I9, Q8NDZ4, Q9H7Y0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
R-HSA-425366	5	15.1×	1e-03
ER-Phagosome pathway	5	10.8×	4e-03
SLC-mediated transmembrane transport	9	8.9×	1e-04
Transport of small molecules	10	4.2×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
intracellular monoatomic cation homeostasis	5	66.9×	2e-06
zinc ion transmembrane transport	7	58.5×	8e-09
intracellular zinc ion homeostasis	7	40.1×	1e-07
amino acid transport	5	18.6×	1e-03
regulation of membrane potential	5	13.7×	3e-03
calcium ion transport	5	10.8×	6e-03
response to ethanol	6	10.5×	3e-03
positive regulation of tumor necrosis factor production	5	9.1×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

485 predictions. Top by Δscore:

Variant	Effect	Δscore
3:143972986:ACAGG:A	donor_loss	1.0000
3:143972988:AGGTA:A	donor_loss	1.0000
3:143972989:GGTA:G	donor_loss	1.0000
3:143972990:GTAG:G	donor_loss	1.0000
3:143985541:A:AG	acceptor_gain	1.0000
3:143985542:G:GG	acceptor_gain	1.0000
3:143985542:GA:G	acceptor_gain	1.0000
3:143985843:CAAA:C	donor_gain	1.0000
3:143989504:TCACA:T	acceptor_loss	1.0000
3:143989505:CACA:C	acceptor_loss	1.0000
3:143989506:ACAGA:A	acceptor_loss	1.0000
3:143989507:C:G	acceptor_gain	1.0000
3:143989507:CAGA:C	acceptor_loss	1.0000
3:143989508:A:AG	acceptor_gain	1.0000
3:143989508:A:C	acceptor_loss	1.0000
3:143989509:G:GA	acceptor_gain	1.0000
3:143989509:GA:G	acceptor_gain	1.0000
3:143989509:GAT:G	acceptor_gain	1.0000
3:143989509:GATA:G	acceptor_gain	1.0000
3:143972990:G:GG	donor_gain	0.9900
3:143985537:TTGTA:T	acceptor_loss	0.9900
3:143985539:GTAG:G	acceptor_loss	0.9900
3:143985539:GTAGA:G	acceptor_gain	0.9900
3:143985540:TAGA:T	acceptor_gain	0.9900
3:143985541:AGAG:A	acceptor_gain	0.9900
3:143985542:G:GT	acceptor_loss	0.9900
3:143985542:GAGT:G	acceptor_gain	0.9900
3:143985542:GAGTT:G	acceptor_gain	0.9900
3:143985842:ACAAA:A	donor_gain	0.9900
3:143985843:CAAAG:C	donor_loss	0.9900

AlphaMissense

2783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:143972505:G:A	C58Y	1.000
3:143972506:C:G	C58W	1.000
3:143972510:G:C	G60R	1.000
3:143972510:G:T	G60C	1.000
3:143972511:G:A	G60D	1.000
3:143972511:G:T	G60V	1.000
3:143972662:G:C	K110N	1.000
3:143972662:G:T	K110N	1.000
3:143972708:T:A	C126S	1.000
3:143972709:G:A	C126Y	1.000
3:143972709:G:C	C126S	1.000
3:143972840:T:A	C170S	1.000
3:143972840:T:C	C170R	1.000
3:143972841:G:C	C170S	1.000
3:143972946:T:C	L205P	1.000
3:143972968:C:A	N212K	1.000
3:143972968:C:G	N212K	1.000
3:143985564:T:A	W227R	1.000
3:143985564:T:C	W227R	1.000
3:143985566:G:C	W227C	1.000
3:143985566:G:T	W227C	1.000
3:143985585:G:A	G234R	1.000
3:143985585:G:C	G234R	1.000
3:143985586:G:A	G234E	1.000
3:143985586:G:T	G234V	1.000
3:143985591:T:C	C236R	1.000
3:143985592:G:A	C236Y	1.000
3:143985593:T:G	C236W	1.000
3:143985594:G:A	G237R	1.000
3:143985594:G:C	G237R	1.000

dbSNP variants (sampled 300 via entrez): RS1000282858 (3:143981515 T>C,G), RS1000527954 (3:143970950 C>A), RS1000871116 (3:143972133 G>A), RS1000938516 (3:143972000 G>T), RS1000942739 (3:143972246 G>A,C), RS1001006234 (3:143987035 C>T), RS1001007930 (3:143983251 C>G,T), RS1001037545 (3:143987246 T>A), RS1001038837 (3:143983532 A>G), RS1001180882 (3:143976274 A>G), RS1001366847 (3:143971465 G>C,T), RS1001773317 (3:143992512 T>G), RS1001825317 (3:143980464 A>G), RS1001876767 (3:143973113 A>G,T), RS1002010098 (3:143984719 G>A)

Disease associations

OMIM: gene MIM:612200 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002934_10	Zinc levels	4.000000e-06
GCST004750_68	Squamous cell lung carcinoma	5.000000e-06
GCST006443_1	Total body bone mineral density	8.000000e-08
GCST007325_285	General risk tolerance (MTAG)	1.000000e-12
GCST007329_19	Automobile speeding propensity	1.000000e-08
GCST010106_3	Conjunctival UV autofluorescence (CUVAF)	4.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0004731	eye measurement
EFO:0010729	sun exposure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Vorinostat	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Dihydrotestosterone	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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