NOL6

Summary

NOL6 (nucleolar protein 6, HGNC:19910) is a protein-coding gene on chromosome 9p13.3, encoding Nucleolar protein 6 (Q9H6R4). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a common-essential gene (DepMap: required in 98.2% of cancer cell lines).

The nucleolus is a dense subnuclear membraneless organelle that assembles around clusters of rRNA genes and functions in ribosome biogenesis. This gene encodes a nucleolar RNA-associated protein that is highly conserved between species. RNase treatment of permeabilized cells indicates that the nucleolar localization is RNA dependent. Further studies suggest that the protein is associated with ribosome biogenesis through an interaction with pre-rRNA primary transcripts. Alternative splicing has been observed at this locus and two splice variants encoding distinct isoforms have been identified.

Source: NCBI Gene 65083 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Strong, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 486 total — 2 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 98.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_022917

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19910
Approved symbol	NOL6
Name	nucleolar protein 6
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	bA311H10.1, Nrap, FLJ21959, MGC14896, MGC14921, MGC20838, UTP22
Ensembl gene	ENSG00000165271
Ensembl biotype	protein_coding
OMIM	611532
Entrez	65083

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000297990, ENST00000353159, ENST00000379470, ENST00000379471, ENST00000464829, ENST00000496319, ENST00000870643

RefSeq mRNA: 2 — MANE Select: NM_022917 NM_022917, NM_139235

CCDS: CCDS6543, CCDS6544

Canonical transcript exons

ENST00000297990 — 26 exons

Exon	Start	End
ENSE00001091756	33468321	33468422
ENSE00001091758	33468508	33468566
ENSE00001091759	33468030	33468145
ENSE00001091760	33469207	33469341
ENSE00001091763	33468752	33468872
ENSE00001091764	33469499	33469667
ENSE00001091767	33465734	33465897
ENSE00001091769	33463831	33463920
ENSE00001091770	33467394	33467516
ENSE00001091773	33466308	33466425
ENSE00001091774	33463247	33463441
ENSE00001091775	33465207	33465359
ENSE00001091776	33464879	33464976
ENSE00001091777	33466569	33466709
ENSE00001091778	33463033	33463134
ENSE00001091779	33466071	33466225
ENSE00001091780	33467114	33467262
ENSE00001091781	33466912	33466987
ENSE00001120742	33467691	33467868
ENSE00001120787	33470012	33470191
ENSE00003484849	33472206	33472412
ENSE00003539824	33472004	33472120
ENSE00003549473	33464037	33464161
ENSE00003686195	33468958	33469121
ENSE00003845921	33473789	33473924
ENSE00003846849	33461353	33462813

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 89.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6736 / max 103.7231, expressed in 1807 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100472	16.0676	1805
100471	1.6059	901

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	89.97	gold quality
lower esophagus mucosa	UBERON:0035834	89.27	gold quality
apex of heart	UBERON:0002098	89.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.18	gold quality
nasal cavity epithelium	UBERON:0005384	88.78	gold quality
gastrocnemius	UBERON:0001388	88.77	gold quality
skin of leg	UBERON:0001511	88.37	gold quality
right testis	UBERON:0004534	88.28	gold quality
left testis	UBERON:0004533	88.23	gold quality
tendon of biceps brachii	UBERON:0008188	88.08	silver quality
esophagus mucosa	UBERON:0002469	87.86	gold quality
skin of abdomen	UBERON:0001416	87.80	gold quality
muscle of leg	UBERON:0001383	87.76	gold quality
adenohypophysis	UBERON:0002196	87.68	gold quality
body of pancreas	UBERON:0001150	87.67	gold quality
right frontal lobe	UBERON:0002810	87.62	gold quality
granulocyte	CL:0000094	87.21	gold quality
pituitary gland	UBERON:0000007	87.14	gold quality
islet of Langerhans	UBERON:0000006	86.95	gold quality
stromal cell of endometrium	CL:0002255	86.86	gold quality
gingival epithelium	UBERON:0001949	86.80	gold quality
upper lobe of left lung	UBERON:0008952	86.78	gold quality
left uterine tube	UBERON:0001303	86.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.60	gold quality
ectocervix	UBERON:0012249	86.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.48	gold quality
pancreas	UBERON:0001264	86.44	gold quality
upper lobe of lung	UBERON:0008948	86.43	gold quality
body of uterus	UBERON:0009853	86.29	gold quality
left adrenal gland cortex	UBERON:0035825	86.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting NOL6, 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-4425	100.00	67.59	1049
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-4763-5P	98.75	63.89	854

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Nucleolar protein 6 promotes cell proliferation and acts as a potential novel prognostic marker for hepatocellular carcinoma. (PMID:34561331)
• NOL6 promotes the proliferation and migration of endometrial cancer cells by regulating TWIST1 expression. (PMID:34607487)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nol6	ENSDARG00000059711
mus_musculus	Nol6	ENSMUSG00000028430
rattus_norvegicus	Nol6	ENSRNOG00000010409
drosophila_melanogaster	Mat89Ba	FBGN0261286
caenorhabditis_elegans		WBGENE00021789

Protein

Protein identifiers

Nucleolar protein 6 — Q9H6R4 (reviewed: Q9H6R4)

Alternative names: Nucleolar RNA-associated protein

All UniProt accessions (3): A0A0A0MRW6, A0A0C4DFX0, Q9H6R4

UniProt curated annotations — full annotation on UniProt →

Function. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with RRP7A; required for NOL6 localization to nucleolus.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Similarity. Belongs to the NRAP family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H6R4-1	1, Alpha, Long	yes
Q9H6R4-2	2, Beta, Mid
Q9H6R4-3	3, Gamma, Short
Q9H6R4-4	4

RefSeq proteins (2): NP_075068, NP_631981 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005554	NOL6/Upt22	Family
IPR035082	Nrap_D1	Domain
IPR035367	Nrap_D2	Domain
IPR035368	Nrap_D3	Domain
IPR035369	Nrap_D4	Domain
IPR035370	Nrap_D5	Domain
IPR035371	Nrap_D6	Domain

Pfam: PF03813, PF17403, PF17404, PF17405, PF17406, PF17407

UniProt features (13 total): modified residue 4, splice variant 3, sequence variant 2, chain 1, region of interest 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6R4-F1	89.07	0.74

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): 56, 283, 289, 811

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 261 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, RNGTGGGC_UNKNOWN, GOBP_RIBOSOME_BIOGENESIS, FREAC2_01, GOBP_MUSCLE_TISSUE_DEVELOPMENT, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CARDIAC_MYOFIBRIL_ASSEMBLY, TGACCTY_ERR1_Q2, GOBP_NUCLEAR_TRANSPORT, MCAATNNNNNGCG_UNKNOWN, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS

GO Biological Process (3): rRNA processing (GO:0006364), tRNA export from nucleus (GO:0006409), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (9): condensed nuclear chromosome (GO:0000794), nucleoplasm (GO:0005654), nucleolus (GO:0005730), mitochondrion (GO:0005739), small-subunit processome (GO:0032040), CURI complex (GO:0032545), UTP-C complex (GO:0034456), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	3
ribosome biogenesis	2
nuclear lumen	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
nucleolus	2
RNA processing	1
rRNA metabolic process	1
RNA export from nucleus	1
tRNA transport	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
cellular anatomical structure	1
cytoplasm	1
preribosome	1
t-UTP complex	1
90S preribosome	1

Protein interactions and networks

STRING

3068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOL6	RRP7A	Q9Y3A4	992
NOL6	CSNK2B	P07312	850
NOL6	CSNK2A1	P19138	796
NOL6	PDCD11	Q14690	796
NOL6	PWP2	Q15269	773
NOL6	UTP18	Q9Y5J1	708
NOL6	UTP6	Q9NYH9	691
NOL6	KRR1	Q13601	678
NOL6	TBL3	Q12788	677
NOL6	NPM1	P06748	669
NOL6	HEATR1	Q9H583	663
NOL6	WDR43	Q15061	643
NOL6	DDX52	Q9Y2R4	628
NOL6	UTP4	Q969X6	610
NOL6	WDR36	Q8NI36	605

IntAct

106 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PIMREG	MTA2	psi-mi:“MI:0914”(association)	0.600
NOL6	JPH3	psi-mi:“MI:0915”(physical association)	0.560
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
NAP1L5	RPS2	psi-mi:“MI:0914”(association)	0.530
RRP7A	ATP4A	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
POP7	RPP40	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
RAB39A	NOL6	psi-mi:“MI:0915”(physical association)	0.400
JUN		psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
TRADD	HNRNPCL2	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (253): NOL6 (Two-hybrid), NOL6 (Affinity Capture-RNA), NOL6 (Affinity Capture-RNA), NOL6 (Affinity Capture-MS), NOL6 (Biochemical Activity), NOL6 (Affinity Capture-MS), NOL6 (Affinity Capture-MS), NOL6 (Affinity Capture-MS), NOL6 (Affinity Capture-MS), NOL6 (Affinity Capture-MS), NOL6 (Co-fractionation), NOL6 (Co-fractionation), NOL6 (Co-fractionation), NOL6 (Co-fractionation), NOL6 (Co-fractionation)

ESM2 similar proteins: A5PJN5, A6H603, A6NFQ2, A6QLU7, D3ZKX9, D3ZQF9, F1LQ70, O00411, O15296, O35936, O70582, O75342, O95932, P09917, P0C869, P12527, P12530, P16050, P16469, P18054, P27479, P39654, P39655, P48999, P51399, P55249, P56201, Q02759, Q08DJ7, Q149M9, Q2KMM4, Q4R7D0, Q5R5N9, Q5R8R3, Q5RBE8, Q643R3, Q6NVG1, Q8BKF1, Q8K4F2, Q8R5K4

Diamond homologs: B4GFN6, B4IBY3, B4K5S6, B4LWT7, B4NIM9, B4PR18, B4QX57, Q295U7, Q5M7P5, Q6NRY2, Q8IH00, Q8R5K4, Q9H6R4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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 modulates host translation machinery	7	26.4×	3e-07
Eukaryotic Translation Initiation	6	22.6×	3e-06
Cap-dependent Translation Initiation	6	22.6×	3e-06
Eukaryotic Translation Elongation	6	20.4×	5e-06
Nonsense-Mediated Decay (NMD)	7	19.9×	9e-07
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	19.9×	6e-06
rRNA modification in the nucleus and cytosol	8	18.3×	4e-07
rRNA processing in the nucleus and cytosol	9	17.6×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	9	18.1×	3e-07
rRNA processing	14	17.6×	3e-11
cytoplasmic translation	10	16.4×	1e-07
negative regulation of translation	7	12.1×	2e-04
regulation of alternative mRNA splicing, via spliceosome	5	10.8×	5e-03
translation	9	8.2×	2e-04
RNA splicing	10	7.8×	9e-05
mRNA processing	9	6.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	11
Uncertain significance	248
Likely benign	75
Benign	100

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1711905	NM_198060.4(NRAP):c.400_407del (p.Cys134fs)	Pathogenic
2579962	NM_198060.4(NRAP):c.3109C>T (p.Arg1037Ter)	Pathogenic
1699323	NM_198060.4(NRAP):c.3301-2A>G	Likely pathogenic
2080715	NM_198060.4(NRAP):c.3604-2A>C	Likely pathogenic
2629310	NM_198060.4(NRAP):c.1843-2A>G	Likely pathogenic
3346392	NM_198060.4(NRAP):c.619del (p.Val207fs)	Likely pathogenic
3372657	NM_198060.4(NRAP):c.4219C>T (p.Gln1407Ter)	Likely pathogenic
3894990	NM_198060.4(NRAP):c.3099G>A (p.Trp1033Ter)	Likely pathogenic
3895320	NM_198060.4(NRAP):c.4197G>A (p.Trp1399Ter)	Likely pathogenic
4278443	NM_198060.4(NRAP):c.2244+1G>A	Likely pathogenic
4820403	NM_198060.4(NRAP):c.994-1G>T	Likely pathogenic
4820486	NM_198060.4(NRAP):c.4206del (p.Ala1403fs)	Likely pathogenic
4820505	NM_198060.4(NRAP):c.3078+1G>T	Likely pathogenic

SpliceAI

5171 predictions. Top by Δscore:

Variant	Effect	Δscore
10:113589660:ACT:A	donor_loss	1.0000
10:113589662:T:TG	donor_loss	1.0000
10:113589663:C:CC	donor_loss	1.0000
10:113589664:A:AC	donor_gain	1.0000
10:113589664:A:T	donor_loss	1.0000
10:113589665:C:CA	donor_gain	1.0000
10:113589685:AGGCC:A	donor_gain	1.0000
10:113589796:ACCT:A	acceptor_loss	1.0000
10:113589798:C:CA	acceptor_loss	1.0000
10:113589799:T:C	acceptor_gain	1.0000
10:113589799:T:TC	acceptor_gain	1.0000
10:113589805:G:GC	acceptor_gain	1.0000
10:113590576:A:AC	donor_gain	1.0000
10:113590577:C:CC	donor_gain	1.0000
10:113590577:CAT:C	donor_gain	1.0000
10:113590577:CATCA:C	donor_gain	1.0000
10:113590581:A:AC	donor_gain	1.0000
10:113590582:C:CC	donor_gain	1.0000
10:113590582:CT:C	donor_gain	1.0000
10:113592160:T:C	donor_gain	1.0000
10:113592192:A:AC	donor_gain	1.0000
10:113592193:C:CC	donor_gain	1.0000
10:113592193:CAT:C	donor_gain	1.0000
10:113592193:CATCA:C	donor_gain	1.0000
10:113592298:CTTT:C	acceptor_gain	1.0000
10:113595616:CACT:C	donor_loss	1.0000
10:113595617:ACTT:A	donor_loss	1.0000
10:113595618:CTTAC:C	donor_loss	1.0000
10:113595619:T:TC	donor_loss	1.0000
10:113595620:T:TG	donor_loss	1.0000

AlphaMissense

7339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33465307:A:G	W861R	0.997
9:33465307:A:T	W861R	0.997
9:33469620:C:A	K202N	0.997
9:33469620:C:G	K202N	0.997
9:33466603:A:T	V686D	0.995
9:33468133:C:G	A441P	0.995
9:33468984:A:G	W334R	0.995
9:33468984:A:T	W334R	0.995
9:33466196:A:G	W747R	0.994
9:33466196:A:T	W747R	0.994
9:33463068:A:G	W1086R	0.993
9:33463068:A:T	W1086R	0.993
9:33466194:C:A	W747C	0.993
9:33466194:C:G	W747C	0.993
9:33469090:G:C	N298K	0.993
9:33469090:G:T	N298K	0.993
9:33469610:A:C	Y206D	0.993
9:33469618:C:G	R203P	0.993
9:33467212:G:C	F592L	0.992
9:33467212:G:T	F592L	0.992
9:33467214:A:G	F592L	0.992
9:33468357:G:C	N424K	0.992
9:33468357:G:T	N424K	0.992
9:33463073:A:T	V1084D	0.990
9:33464924:A:G	W912R	0.990
9:33464924:A:T	W912R	0.990
9:33466078:A:T	V786D	0.990
9:33469649:C:G	D193H	0.990
9:33466220:A:G	C739R	0.989
9:33468971:C:G	R338P	0.989

dbSNP variants (sampled 300 via entrez): RS1000063746 (9:33461111 A>C,G), RS1000306817 (9:33472700 C>T), RS1000394347 (9:33464244 C>G), RS1000519922 (9:33460940 G>A,C), RS1000553386 (9:33465498 G>A), RS1000672183 (9:33470017 G>A,C), RS1000719499 (9:33470915 T>C,G), RS1000993163 (9:33474902 T>C), RS1001128649 (9:33474565 C>T), RS1001142430 (9:33475581 G>T), RS1002170463 (9:33464472 A>G), RS1002318093 (9:33469769 C>T), RS1002460557 (9:33474444 T>G), RS1002713720 (9:33468005 C>A,T), RS1002784898 (9:33474419 T>C,G)

Disease associations

OMIM: gene MIM:611532 | disease phenotypes: MIM:618225

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy	Strong	AR

Mondo (2): dilated cardiomyopathy (MONDO:0005021), mitochondrial complex I deficiency, nuclear type 4 (MONDO:0032609)

Orphanet (1): Dilated cardiomyopathy (Orphanet:217604)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006417_43	Plasma factor VII activating protease levels	5.000000e-06
GCST006979_609	Heel bone mineral density	5.000000e-10
GCST010152_16	Neuroblastoma or malignant cutaneous melanoma	3.000000e-07
GCST010919_5	QT interval	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004682	QT interval

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
perfluoro-n-nonanoic acid	decreases expression, increases expression	2
Estradiol	increases expression	2
Nickel	increases expression	2
bisphenol F	decreases expression, affects cotreatment	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
bisphenol S	affects expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Amiodarone	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy