RUNDC3A

Summary

RUNDC3A (RUN domain containing 3A, HGNC:16984) is a protein-coding gene on chromosome 17q21.31, encoding RUN domain-containing protein 3A (Q59EK9). May act as an effector of RAP2A in neuronal cells.

Predicted to enable GTPase regulator activity. Predicted to be involved in positive regulation of cGMP-mediated signaling. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 10900 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001144825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16984
Approved symbol	RUNDC3A
Name	RUN domain containing 3A
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	RPIP8, RAP2IP
Ensembl gene	ENSG00000108309
Ensembl biotype	protein_coding
OMIM	605448
Entrez	10900

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 4 retained_intron

ENST00000225441, ENST00000426726, ENST00000587483, ENST00000588564, ENST00000590834, ENST00000590941, ENST00000593079, ENST00000906568, ENST00000906569, ENST00000906570, ENST00000906571, ENST00000906572, ENST00000906573, ENST00000951039, ENST00000951040, ENST00000951041

RefSeq mRNA: 3 — MANE Select: NM_001144825 NM_001144825, NM_001144826, NM_006695

CCDS: CCDS45698, CCDS45699, CCDS59294

Canonical transcript exons

ENST00000426726 — 11 exons

Exon	Start	End
ENSE00001059646	44316385	44316522
ENSE00001722399	44318096	44318670
ENSE00002791075	44308601	44308939
ENSE00003482439	44314929	44315009
ENSE00003520030	44313418	44313503
ENSE00003521829	44312580	44312695
ENSE00003541296	44314735	44314824
ENSE00003633967	44315155	44315320
ENSE00003638676	44313104	44313252
ENSE00003675234	44315452	44315609
ENSE00003685982	44316619	44316725

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.47.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7658 / max 251.6303, expressed in 302 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161130	4.0658	256
161131	1.5726	181
161132	0.0780	52
208209	0.0351	21
161129	0.0143	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	99.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.45	gold quality
cerebellar hemisphere	UBERON:0002245	99.39	gold quality
cerebellar cortex	UBERON:0002129	99.35	gold quality
cingulate cortex	UBERON:0003027	99.16	gold quality
anterior cingulate cortex	UBERON:0009835	99.14	gold quality
prefrontal cortex	UBERON:0000451	99.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.09	gold quality
amygdala	UBERON:0001876	99.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.94	gold quality
cerebellum	UBERON:0002037	98.92	gold quality
frontal cortex	UBERON:0001870	98.86	gold quality
nucleus accumbens	UBERON:0001882	98.79	gold quality
caudate nucleus	UBERON:0001873	98.61	gold quality
neocortex	UBERON:0001950	98.57	gold quality
Ammon’s horn	UBERON:0001954	98.50	gold quality
cerebral cortex	UBERON:0000956	98.41	gold quality
putamen	UBERON:0001874	98.40	gold quality
superior frontal gyrus	UBERON:0002661	98.39	gold quality
temporal lobe	UBERON:0001871	98.37	gold quality
telencephalon	UBERON:0001893	98.13	gold quality
forebrain	UBERON:0001890	97.91	gold quality
orbitofrontal cortex	UBERON:0004167	97.80	gold quality
postcentral gyrus	UBERON:0002581	97.75	gold quality
CA1 field of hippocampus	UBERON:0003881	97.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.75	gold quality
brain	UBERON:0000955	97.73	gold quality
parietal lobe	UBERON:0001872	97.73	gold quality
central nervous system	UBERON:0001017	97.63	gold quality
entorhinal cortex	UBERON:0002728	97.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	4.29
E-ANND-3	yes	3.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting RUNDC3A, 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-4283	100.00	66.42	2097
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
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-4668-5P	99.79	70.58	3782
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-6769B-3P	97.41	65.53	1036

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rundc3ab	ENSDARG00000002546
danio_rerio	rundc3aa	ENSDARG00000007245
mus_musculus	Rundc3a	ENSMUSG00000006575
rattus_norvegicus	Rundc3a	ENSRNOG00000020970
drosophila_melanogaster	CG6051	FBGN0039492
drosophila_melanogaster	CG31064	FBGN0051064
caenorhabditis_elegans		WBGENE00003084

Paralogs (13): RUFY3 (ENSG00000018189), ZFYVE16 (ENSG00000039319), SNX29 (ENSG00000048471), ZFYVE26 (ENSG00000072121), RUNDC3B (ENSG00000105784), PLEKHM2 (ENSG00000116786), ZFYVE28 (ENSG00000159733), ZFYVE1 (ENSG00000165861), ZFYVE19 (ENSG00000166140), PLEKHF1 (ENSG00000166289), PLEKHF2 (ENSG00000175895), RUFY1 (ENSG00000176783), RUFY2 (ENSG00000204130)

Protein

Protein identifiers

RUN domain-containing protein 3A — Q59EK9 (reviewed: Q59EK9)

Alternative names: Rap2-interacting protein 8

All UniProt accessions (1): Q59EK9

UniProt curated annotations — full annotation on UniProt →

Function. May act as an effector of RAP2A in neuronal cells.

Subunit / interactions. Interacts with the GTP-bound form of RAP2A.

Similarity. Belongs to the RUNDC3 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q59EK9-1	1	yes
Q59EK9-2	2
Q59EK9-3	3
Q59EK9-4	4

RefSeq proteins (3): NP_001138297, NP_001138298, NP_006686 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004012	Run_dom	Domain
IPR037213	Run_dom_sf	Homologous_superfamily
IPR047338	RUN_RUNDC3A	Domain
IPR047340	RUNDC3A_B	Family

Pfam: PF02759

UniProt features (16 total): modified residue 4, splice variant 4, region of interest 3, chain 1, domain 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q59EK9-F1	69.56	0.43

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 (4): 419, 215, 232, 416

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): ATF_B, AP1_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CREBP1_Q2, GGGTGGRR_PAX4_03, CREB_Q4, MODULE_66, MODULE_379, ATF1_Q6, BACH2_01, GNF2_TM4SF2, E4F1_Q6, TGANTCA_AP1_C, ATF3_Q6, CREB_Q2_01

GO Biological Process (2): small GTPase-mediated signal transduction (GO:0007264), obsolete positive regulation of cGMP-mediated signaling (GO:0010753)

GO Molecular Function (2): GTPase regulator activity (GO:0030695), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	1
GTPase activity	1
nucleoside-triphosphatase regulator activity	1
binding	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RUNDC3A	SLC25A39	Q9BZJ4	892
RUNDC3A	RAP2A	P10114	819
RUNDC3A	RUSC1	Q9BVN2	793
RUNDC3A	GRN	P23781	659
RUNDC3A	TARDBP	Q13148	547
RUNDC3A	LRPAP1	P30533	542
RUNDC3A	TMEM145	Q8NBT3	531
RUNDC3A	TMEM19	Q96HH6	506
RUNDC3A	RAP2B	P17964	488
RUNDC3A	DCAKD	Q8WVC6	483
RUNDC3A	ANKRD9	Q96BM1	480
RUNDC3A	AP3B2	Q13367	470
RUNDC3A	ZNF706	Q9Y5V0	464
RUNDC3A	ATXN7L3	Q14CW9	440
RUNDC3A	UBB	P02248	429

IntAct

70 interactions, top by confidence:

A	B	Type	Score
EIF3E	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.670
RAP2B	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.670
RUNDC3A	AP1M1	psi-mi:“MI:0915”(physical association)	0.670
RUNDC3A	EIF3E	psi-mi:“MI:0915”(physical association)	0.670
AP1M1	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.670
RUNDC3A	RAP2B	psi-mi:“MI:0915”(physical association)	0.670
RUNDC3A	TFPT	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
RUNDC3A	MAGEB4	psi-mi:“MI:0915”(physical association)	0.560
DDX6	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
GEM	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
RUNDC3A	TBRG1	psi-mi:“MI:0915”(physical association)	0.560
FAM161A	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
RUNDC3A	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
MAGOHB	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
CCNL2	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
RUNDC3A	ZNF587	psi-mi:“MI:0915”(physical association)	0.560
SYT17	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
RUNDC3A	ARMC7	psi-mi:“MI:0915”(physical association)	0.560
MRPL15	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
TFPT	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
RUNDC3A	SDCBP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (101): RUNDC3A (Two-hybrid), RUNDC3A (Two-hybrid), RUNDC3A (Two-hybrid), RUNDC3A (Two-hybrid), RUNDC3A (Two-hybrid), RUNDC3A (Two-hybrid), RUNDC3A (Two-hybrid), MRPL15 (Two-hybrid), TFPT (Two-hybrid), SYT17 (Two-hybrid), MAGOHB (Two-hybrid), ARMC7 (Two-hybrid), MYO15B (Two-hybrid), CCNL2 (Two-hybrid), FAM161A (Two-hybrid)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A0JMA8, A1A535, A1A5P5, A1L1K1, A2AVJ5, A7YDW0, B3MJV4, B4MV81, O00443, O08576, O17237, Q0V9V7, Q12923, Q14D04, Q17QK1, Q1LYM3, Q2NKQ1, Q3UGY8, Q59EK9, Q5EB20, Q5JWR5, Q5PQS3, Q5R565, Q5RAY1, Q5TH69, Q5U245, Q5U3W3, Q5XHG1, Q61194, Q61QK6, Q64512, Q6ING4, Q6MZQ0, Q6ZUJ8, Q7Z3E5, Q803Q4, Q80U12, Q8BPQ7

Diamond homologs: A7YDW0, O08576, Q08E29, Q0V9V7, Q17QK1, Q3B7K9, Q4R7B9, Q59EK9, Q5FVJ0, Q5NVC2, Q5R4V2, Q5R565, Q5R5R4, Q5U3W3, Q6PDC0, Q7L099, Q8BIJ7, Q8R4C2, Q8WXA3, Q96NL0, Q96T51, Q9D394, A2RSQ0, Q08DX0, Q6NXD8, Q6ZUT9, Q8TEQ0, Q9D3S3, G3V7Q0, Q6IQ26, Q6PAL8, Q6ZNE9, A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A2QWA2, A3LX75, A4QTV1, A8QCE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44308913:GC:G	donor_gain	1.0000
17:44308935:TGCAG:T	donor_loss	1.0000
17:44308940:G:A	donor_loss	1.0000
17:44308941:T:A	donor_loss	1.0000
17:44312566:A:AG	acceptor_gain	1.0000
17:44312567:C:G	acceptor_gain	1.0000
17:44312570:C:A	acceptor_gain	1.0000
17:44312573:C:A	acceptor_gain	1.0000
17:44312576:CCAGG:C	acceptor_loss	1.0000
17:44312577:CAGGT:C	acceptor_loss	1.0000
17:44312578:A:AG	acceptor_gain	1.0000
17:44312578:A:T	acceptor_loss	1.0000
17:44312578:AG:A	acceptor_gain	1.0000
17:44312579:G:GC	acceptor_gain	1.0000
17:44312579:GG:G	acceptor_gain	1.0000
17:44312579:GGT:G	acceptor_gain	1.0000
17:44312579:GGTT:G	acceptor_gain	1.0000
17:44312579:GGTTC:G	acceptor_gain	1.0000
17:44312691:CAAAG:C	donor_loss	1.0000
17:44312692:AAAGG:A	donor_loss	1.0000
17:44312693:AAGG:A	donor_loss	1.0000
17:44312694:AGGTG:A	donor_loss	1.0000
17:44312695:GGT:G	donor_loss	1.0000
17:44312696:GT:G	donor_loss	1.0000
17:44314730:CACAG:C	acceptor_loss	1.0000
17:44314731:ACAG:A	acceptor_loss	1.0000
17:44314732:CAGA:C	acceptor_loss	1.0000
17:44314733:A:AG	acceptor_gain	1.0000
17:44314733:AGAC:A	acceptor_gain	1.0000
17:44314733:AGACG:A	acceptor_gain	1.0000

AlphaMissense

2911 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44308924:T:C	L31P	1.000
17:44312597:T:C	L42P	1.000
17:44313160:T:A	W94R	1.000
17:44313160:T:C	W94R	1.000
17:44313427:T:A	W128R	1.000
17:44313427:T:C	W128R	1.000
17:44313443:T:C	L133P	1.000
17:44313455:G:C	R137P	1.000
17:44315459:T:C	L268P	1.000
17:44315468:T:C	L271P	1.000
17:44315597:T:C	L314P	1.000
17:44308922:C:A	N30K	0.999
17:44308922:C:G	N30K	0.999
17:44308935:T:C	C35R	0.999
17:44312597:T:G	L42R	0.999
17:44312652:T:A	N60K	0.999
17:44312652:T:G	N60K	0.999
17:44312678:T:C	L69P	0.999
17:44313162:G:C	W94C	0.999
17:44313162:G:T	W94C	0.999
17:44313179:C:A	A100D	0.999
17:44313215:T:A	I112N	0.999
17:44313252:G:C	K124N	0.999
17:44313252:G:T	K124N	0.999
17:44313418:G:C	G125R	0.999
17:44313419:G:A	G125D	0.999
17:44313428:G:C	W128S	0.999
17:44313434:G:C	R130P	0.999
17:44313443:T:G	L133R	0.999
17:44313446:T:C	M134T	0.999

dbSNP variants (sampled 300 via entrez): RS1000305802 (17:44311959 C>T), RS1000564459 (17:44316969 C>G,T), RS1000737370 (17:44317394 C>A,G,T), RS1000755048 (17:44310583 T>G), RS1000808975 (17:44310620 C>A,G,T), RS1000861512 (17:44310294 A>G), RS1001026896 (17:44317186 GCTTA>G), RS1001344914 (17:44313475 A>G), RS1001417048 (17:44313661 C>A), RS1001511534 (17:44307130 CAG>C), RS1001578650 (17:44313494 G>A), RS1001772722 (17:44307035 C>T), RS1001922960 (17:44313785 G>A), RS1002296812 (17:44318312 C>T), RS1002351074 (17:44311721 G>T)

Disease associations

OMIM: gene MIM:605448 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
entinostat	decreases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Camptothecin	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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