DNAJC27

Summary

DNAJC27 (DnaJ heat shock protein family (Hsp40) member C27, HGNC:30290) is a protein-coding gene on chromosome 2p23.3, encoding DnaJ homolog subfamily C member 27 (Q9NZQ0). GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed.

Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport. Predicted to be located in cytoplasmic vesicle and nucleus.

Source: NCBI Gene 51277 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_016544

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30290
Approved symbol	DNAJC27
Name	DnaJ heat shock protein family (Hsp40) member C27
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	RabJS
Ensembl gene	ENSG00000115137
Ensembl biotype	protein_coding
OMIM	613527
Entrez	51277

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000264711, ENST00000380809, ENST00000468467, ENST00000468750, ENST00000492985, ENST00000494239, ENST00000534855

RefSeq mRNA: 2 — MANE Select: NM_016544 NM_001198559, NM_016544

CCDS: CCDS1716, CCDS74493

Canonical transcript exons

ENST00000264711 — 7 exons

Exon	Start	End
ENSE00001227172	24943642	24947748
ENSE00003525169	24951394	24951554
ENSE00003606210	24967211	24967293
ENSE00003625666	24957810	24957974
ENSE00003658372	24957043	24957165
ENSE00003731272	24963405	24963474
ENSE00003893005	24971818	24971955

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 92.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6960 / max 96.2539, expressed in 1235 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27344	1.6232	705
27345	1.3245	590
27343	0.6623	309
27346	0.0860	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	92.20	gold quality
middle temporal gyrus	UBERON:0002771	91.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.48	gold quality
oviduct epithelium	UBERON:0004804	90.60	gold quality
sperm	CL:0000019	89.43	gold quality
secondary oocyte	CL:0000655	88.27	gold quality
buccal mucosa cell	CL:0002336	87.40	gold quality
pons	UBERON:0000988	87.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.44	gold quality
substantia nigra pars compacta	UBERON:0001965	85.60	gold quality
cerebellar vermis	UBERON:0004720	84.37	gold quality
superior vestibular nucleus	UBERON:0007227	84.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.31	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.94	gold quality
adult organism	UBERON:0007023	83.90	gold quality
primary visual cortex	UBERON:0002436	83.14	gold quality
occipital lobe	UBERON:0002021	82.94	gold quality
lateral globus pallidus	UBERON:0002476	82.41	gold quality
deltoid	UBERON:0001476	82.26	gold quality
corpus callosum	UBERON:0002336	82.24	gold quality
heart right ventricle	UBERON:0002080	82.15	gold quality
testis	UBERON:0000473	81.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.71	gold quality
medulla oblongata	UBERON:0001896	81.49	gold quality
calcaneal tendon	UBERON:0003701	81.44	gold quality
superior frontal gyrus	UBERON:0002661	81.29	gold quality
parietal lobe	UBERON:0001872	81.12	gold quality
postcentral gyrus	UBERON:0002581	80.92	gold quality
right testis	UBERON:0004534	80.80	gold quality
prefrontal cortex	UBERON:0000451	80.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

200 targeting DNAJC27, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 1)

• these data suggest that RBJ may be an oncogenic Ras-related small GTPase mediating nuclear accumulation of active MEK1/MEK2 in tumor progression. (PMID:24746703)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc27	ENSDARG00000070916
mus_musculus	Dnajc27	ENSMUSG00000020657
rattus_norvegicus	Dnajc27	ENSRNOG00000003988

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955), RAB41 (ENSG00000147127)

Protein

Protein identifiers

DnaJ homolog subfamily C member 27 — Q9NZQ0 (reviewed: Q9NZQ0)

Alternative names: Rab and DnaJ domain-containing protein

All UniProt accessions (1): Q9NZQ0

UniProt curated annotations — full annotation on UniProt →

Function. GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed. May act as a nuclear scaffold for MAPK1, probably by association with MAPK1 nuclear export signal leading to enhanced ERK1/ERK2 signaling.

Subunit / interactions. Interacts directly with MAPK1 (wild-type and kinase-deficient forms). Interacts directly (in GTP-bound form) with MAP2K1 (wild-type and kinase-deficient forms).

Subcellular location. Nucleus.

Tissue specificity. Overexpressed in gastrointestinal cancers; expression correlates with later tumor-node-metastasis stages of colorectal cancers.

Miscellaneous. DNAJC27/RBJ knockdown in several colorectal cancer cell lines is correlated to inhibition of MEK/ERK activation, cell proliferation, colony formation and in vivo tumor growth.

Similarity. Belongs to the small GTPase superfamily. Rab family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NZQ0-1	1	yes
Q9NZQ0-2	2
Q9NZQ0-3	3

RefSeq proteins (2): NP_001185488, NP_057628* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036869	J_dom_sf	Homologous_superfamily

Pfam: PF00071, PF00226

UniProt features (15 total): helix 4, splice variant 4, binding site 3, chain 1, domain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YS8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZQ0-F1	90.75	0.78

Functional residue map

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

Ligand- & substrate-binding residues (3): 23–30; 71–75; 134–137

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, CREBP1_Q2, TGACCTY_ERR1_Q2, E4F1_Q6, CREB_Q2_01, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GATA2_01, CREB_Q3, GOBP_POSITIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, MODULE_207, GOBP_ERK1_AND_ERK2_CASCADE, CREBP1CJUN_01

GO Biological Process (2): intracellular protein transport (GO:0006886), positive regulation of ERK1 and ERK2 cascade (GO:0070374)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	1
protein transport	1
intracellular transport	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
membrane-bounded organelle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC27	ADCY3	O60266	740
DNAJC27	ADCY8	P40145	728
DNAJC27	SEC16B	Q96JE7	666
DNAJC27	TMEM160	Q9NX00	621
DNAJC27	DNAJC9	Q8WXX5	610
DNAJC27	DNAJC28	Q9NX36	610
DNAJC27	GNPDA2	Q8TDQ7	608
DNAJC27	ZNF608	Q9ULD9	606
DNAJC27	POC5	Q8NA72	604
DNAJC27	TMEM18	Q96B42	601
DNAJC27	QPCTL	Q9NXS2	597
DNAJC27	NUDT3	O95989	583
DNAJC27	V9GXZ4	V9GXZ4	581
DNAJC27	TNNI3K	Q59H18	572
DNAJC27	MTIF3	Q9H2K0	572

IntAct

9 interactions, top by confidence:

A	B	Type	Score
DNAJC27	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	DNAJC27	psi-mi:“MI:0915”(physical association)	0.720
DNAJC27	METAP2	psi-mi:“MI:0914”(association)	0.350
DNAJC27	TFCP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): DNAJC27 (Two-hybrid), TFCP2 (Two-hybrid), ANP32B (Affinity Capture-MS), DNMT1 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FAM184B (Affinity Capture-MS), CAPRIN1 (Affinity Capture-MS), ACP1 (Affinity Capture-MS), FAM184A (Affinity Capture-MS), GRPEL1 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), FAM184A (Proximity Label-MS), FAM184B (Proximity Label-MS), TFCP2 (Proximity Label-MS), METAP2 (Affinity Capture-MS)

ESM2 similar proteins: A5D7F5, C8VQY7, G4MYS1, H9BW96, I1RMF2, O04157, O24461, O76742, O94655, O97572, P09527, P18067, P24408, P31022, P36411, P36864, P51149, P51150, P51151, P91580, P93267, P97950, Q14088, Q39573, Q3T0F5, Q40787, Q41640, Q43463, Q54QR3, Q5M7D1, Q5R615, Q5R9Y4, Q5RDE5, Q5ZHV1, Q6IMK3, Q6IML7, Q6IMM1, Q7ZYF1, Q8CFP6, Q948K8

Diamond homologs: A5D7F5, F1PTE3, H9BW96, O18333, O23561, O24461, P05712, P05714, P10536, P16976, P17609, P20338, P20791, P22125, P24409, P31022, P31584, P34140, P35282, P35286, P36409, P36410, P36411, P36861, P36862, P36863, P36864, P41924, P49103, P49104, P51146, P51153, P53994, P55745, P56371, P59279, P61017, P61018, P61019, P61026

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1343 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24947611:A:AC	donor_gain	1.0000
2:24947612:C:CC	donor_gain	1.0000
2:24947612:CTTT:C	donor_gain	1.0000
2:24947613:TTTC:T	donor_gain	1.0000
2:24947614:TTCT:T	donor_gain	1.0000
2:24947615:T:A	donor_gain	1.0000
2:24947747:CC:C	acceptor_gain	1.0000
2:24947748:CC:C	acceptor_gain	1.0000
2:24947748:CCTGG:C	acceptor_loss	1.0000
2:24947749:C:CC	acceptor_gain	1.0000
2:24947749:CTG:C	acceptor_loss	1.0000
2:24957038:CTTA:C	donor_loss	1.0000
2:24957041:A:AC	donor_gain	1.0000
2:24957041:A:T	donor_loss	1.0000
2:24957041:AC:A	donor_gain	1.0000
2:24957042:C:CC	donor_gain	1.0000
2:24957042:CC:C	donor_gain	1.0000
2:24957161:TCAAT:T	acceptor_gain	1.0000
2:24957162:CAAT:C	acceptor_gain	1.0000
2:24957162:CAATC:C	acceptor_gain	1.0000
2:24957163:AAT:A	acceptor_gain	1.0000
2:24957164:AT:A	acceptor_gain	1.0000
2:24957164:ATC:A	acceptor_loss	1.0000
2:24957165:TCTG:T	acceptor_loss	1.0000
2:24957166:C:CC	acceptor_gain	1.0000
2:24957166:C:CG	acceptor_loss	1.0000
2:24957171:A:AC	acceptor_gain	1.0000
2:24957171:A:C	acceptor_gain	1.0000
2:24957841:T:TA	donor_gain	1.0000
2:24967205:ACTT:A	donor_loss	1.0000

AlphaMissense

1822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24947664:G:C	F258L	1.000
2:24947664:G:T	F258L	1.000
2:24947666:A:G	F258L	1.000
2:24947705:G:C	H245D	1.000
2:24947716:G:T	A241D	1.000
2:24957081:A:G	S164P	1.000
2:24957819:A:C	C132W	1.000
2:24957821:A:G	C132R	1.000
2:24957823:A:T	V131D	1.000
2:24957943:C:T	G91D	1.000
2:24957944:C:G	G91R	1.000
2:24957960:A:C	F85L	1.000
2:24957960:A:T	F85L	1.000
2:24957961:A:C	F85C	1.000
2:24957961:A:G	F85S	1.000
2:24957962:A:G	F85L	1.000
2:24963411:G:C	F78L	1.000
2:24963411:G:T	F78L	1.000
2:24963413:A:G	F78L	1.000
2:24963424:C:T	G74E	1.000
2:24963425:C:G	G74R	1.000
2:24963425:C:T	G74R	1.000
2:24963427:G:T	A73D	1.000
2:24963432:A:C	D71E	1.000
2:24963432:A:T	D71E	1.000
2:24963433:T:A	D71V	1.000
2:24963433:T:C	D71G	1.000
2:24963433:T:G	D71A	1.000
2:24963434:C:A	D71Y	1.000
2:24963434:C:G	D71H	1.000

dbSNP variants (sampled 300 via entrez): RS1000054115 (2:24958892 T>C), RS1000098275 (2:24966471 C>A,G,T), RS1000106106 (2:24948887 C>G), RS1000118260 (2:24965700 A>T), RS1000185514 (2:24952281 T>C), RS1000413059 (2:24947129 C>A,T), RS1000441176 (2:24945584 A>G), RS1000511604 (2:24958648 G>A), RS1000824382 (2:24945960 C>T), RS1000888539 (2:24947474 C>G), RS1000897617 (2:24952085 G>T), RS1001066619 (2:24965795 CTA>C), RS1001105390 (2:24958680 G>A,T), RS1001181282 (2:24946930 C>A,G,T), RS1001237160 (2:24950564 G>C)

Disease associations

OMIM: gene MIM:613527 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000175_18	Height	8.000000e-07
GCST000817_56	Height	7.000000e-16
GCST000830_38	Body mass index	6.000000e-22
GCST001255_1	Type 1 diabetes	4.000000e-09
GCST001415_7	Body mass index	1.000000e-13
GCST001876_3	Pubertal anthropometrics	1.000000e-08
GCST002461_13	Body mass index	1.000000e-10
GCST002702_112	Height	1.000000e-08
GCST004131_107	Inflammatory bowel disease	3.000000e-07
GCST004132_38	Crohn’s disease	9.000000e-08
GCST004904_145	Body mass index	3.000000e-32
GCST004904_215	Body mass index	5.000000e-13
GCST005950_4	Body mass index x sex x age interaction (4df test)	5.000000e-26
GCST005951_195	Body mass index	3.000000e-24
GCST005952_4	Body mass index (age>50)	5.000000e-09
GCST005953_10	Body mass index (age <50)	6.000000e-20
GCST007240_5	Obese vs. thin	3.000000e-17
GCST007241_5	Obesity (extreme)	9.000000e-23
GCST007293_13	Body fat distribution (arm fat ratio)	2.000000e-39
GCST007293_41	Body fat distribution (arm fat ratio)	5.000000e-22
GCST007293_5	Body fat distribution (arm fat ratio)	2.000000e-21
GCST007294_128	Body fat distribution (trunk fat ratio)	7.000000e-06
GCST007294_94	Body fat distribution (trunk fat ratio)	9.000000e-10
GCST008758_54	Pre-treatment viral load in HIV-1 infection	1.000000e-15
GCST008839_91	Height	2.000000e-27
GCST90000025_800	Appendicular lean mass	1.000000e-39
GCST90020028_429	Hip circumference adjusted for BMI	7.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0001382	puberty
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007041	obese body mass index status
EFO:0004341	body fat distribution
EFO:0010125	viral load
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	decreases phosphorylation	1
resorcinol	decreases expression	1
diallyl trisulfide	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Decitabine	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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