JRK

Summary

JRK (Jrk helix-turn-helix protein, HGNC:6199) is a protein-coding gene on chromosome 8q24.3, encoding Jerky protein homolog (O75564). May bind DNA.

This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8629 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 67 total
• Phenotypes (HPO): 30
• MANE Select transcript: NM_003724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6199
Approved symbol	JRK
Name	Jrk helix-turn-helix protein
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	JH8, jerky
Ensembl gene	ENSG00000234616
Ensembl biotype	protein_coding
OMIM	603210
Entrez	8629

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000503272, ENST00000506774, ENST00000571961, ENST00000585503, ENST00000587499, ENST00000587883, ENST00000591180, ENST00000591357, ENST00000612905, ENST00000614134, ENST00000615982, ENST00000895841, ENST00000895842

RefSeq mRNA: 3 — MANE Select: NM_003724 NM_001077527, NM_001279352, NM_003724

CCDS: CCDS75796, CCDS75797

Canonical transcript exons

ENST00000612905 — 2 exons

Exon	Start	End
ENSE00003741733	142657460	142666520
ENSE00003897332	142669932	142669967

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 92.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4738 / max 44.4775, expressed in 1689 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95413	5.4427	1637
95415	1.0310	345

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	92.29	gold quality
paraflocculus	UBERON:0005351	91.74	gold quality
sural nerve	UBERON:0015488	90.90	gold quality
endometrium epithelium	UBERON:0004811	90.23	gold quality
frontal pole	UBERON:0002795	89.95	silver quality
olfactory bulb	UBERON:0002264	89.80	gold quality
lower esophagus mucosa	UBERON:0035834	89.57	gold quality
body of stomach	UBERON:0001161	89.10	gold quality
tendon of biceps brachii	UBERON:0008188	88.89	gold quality
pancreatic ductal cell	CL:0002079	88.86	silver quality
trabecular bone tissue	UBERON:0002483	88.84	gold quality
nasal cavity epithelium	UBERON:0005384	88.35	gold quality
triceps brachii	UBERON:0001509	88.19	gold quality
middle frontal gyrus	UBERON:0002702	87.91	silver quality
stomach	UBERON:0000945	87.70	gold quality
cardia of stomach	UBERON:0001162	87.67	gold quality
gluteal muscle	UBERON:0002000	87.67	gold quality
thymus	UBERON:0002370	87.27	gold quality
lateral globus pallidus	UBERON:0002476	87.25	gold quality
vena cava	UBERON:0004087	86.75	gold quality
vastus lateralis	UBERON:0001379	86.71	silver quality
upper arm skin	UBERON:0004263	86.59	silver quality
cervix squamous epithelium	UBERON:0006922	86.31	silver quality
quadriceps femoris	UBERON:0001377	86.15	silver quality
diaphragm	UBERON:0001103	86.06	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.02	gold quality
pylorus	UBERON:0001166	85.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.71	gold quality
fundus of stomach	UBERON:0001160	85.49	gold quality
renal medulla	UBERON:0000362	85.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-111727	no	2042.77
E-ANND-3	no	3.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

186 targeting JRK, 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-340-5P	100.00	72.50	4437
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 3)

• JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of beta-catenin target genes and increased cell proliferation (PMID:26455321)
• in the adult intestine, Ebd acts independently of Ewg in physiological Wnt signaling, but cooperates with Ewg to induce the hyperactivation of Wnt target gene expression following Apc1 loss. These findings have relevance for human tumorigenesis, as Jerky (JRK/JH8), the human Ebd homolog, promotes Wnt pathway hyperactivation and is overexpressed in colorectal, breast, and ovarian cancers (PMID:28708826)
• JRK binds satellite III DNA and is necessary for the heat shock response. (PMID:38946594)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Jrk	ENSMUSG00000046380
rattus_norvegicus	Jrk	ENSRNOG00000027238

Paralogs (12): CENPB (ENSG00000125817), TIGD7 (ENSG00000140993), POGK (ENSG00000143157), POGZ (ENSG00000143442), TIGD6 (ENSG00000164296), TIGD4 (ENSG00000169989), TIGD3 (ENSG00000173825), TIGD5 (ENSG00000179886), TIGD2 (ENSG00000180346), JRKL (ENSG00000183340), TIGD1 (ENSG00000221944), (ENSG00000293642)

Protein

Protein identifiers

Jerky protein homolog — O75564 (reviewed: O75564)

All UniProt accessions (2): A0A087WZD9, O75564

UniProt curated annotations — full annotation on UniProt →

Function. May bind DNA.

Subcellular location. Nucleus.

Tissue specificity. Expressed ubiquitously.

Similarity. Belongs to the tigger transposable element derived protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75564-1	1	yes
O75564-2	2

RefSeq proteins (3): NP_001070995, NP_001266281, NP_003715* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004875	DDE_SF_endonuclease_dom	Domain
IPR006600	HTH_CenpB_DNA-bd_dom	Domain
IPR007889	HTH_Psq	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR050863	CenT-Element_Derived	Family

Pfam: PF03184, PF03221, PF04218

UniProt features (11 total): domain 3, DNA-binding region 2, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75564-F1	71.94	0.25

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 (1): 414

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 243 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_MSH3, MORF_BRCA1, MORF_ATRX, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, MORF_ESR1, LINDSTEDT_DENDRITIC_CELL_MATURATION_B, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, MORF_PPP5C, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_FANCG, LIAO_METASTASIS, MORF_RAP1A, GOBP_POSITIVE_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, LEE_AGING_CEREBELLUM_DN

GO Biological Process (1): positive regulation of canonical Wnt signaling pathway (GO:0090263)

GO Molecular Function (4): DNA binding (GO:0003677), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JRK	ME2	P23368	825
JRK	PSCA	O43653	602
JRK	OPRM1	P35372	581
JRK	CACNA1A	P78510	527
JRK	CLCN2	P51788	512
JRK	KCNQ3	O43525	509
JRK	CACNA1H	O95180	500
JRK	SLC6A1	P30531	494
JRK	GABRD	O14764	452
JRK	THEM6	Q8WUY1	425
JRK	FGFR2	P18443	424
JRK	GABRG2	P18507	395
JRK	POGK	Q9P215	361
JRK	RFLNA	Q6ZTI6	359
JRK	NAIF1	Q69YI7	355

IntAct

16 interactions, top by confidence:

A	B	Type	Score
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
CTNNB1	JRK	psi-mi:“MI:0915”(physical association)	0.580
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
Lef1	JRK	psi-mi:“MI:0915”(physical association)	0.500
JRK	Lef1	psi-mi:“MI:0914”(association)	0.500
PYGO2	JRK	psi-mi:“MI:0915”(physical association)	0.400
JRK	TCF7L2	psi-mi:“MI:0915”(physical association)	0.400
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
VWA5A	PIPSL	psi-mi:“MI:0914”(association)	0.350
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.350
VWA5A	GTPBP6	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A0G2K1Q8, B0BN95, B2RRL2, O14423, O43422, O46510, O60108, O75564, O96006, P49777, P55205, P55211, Q01841, Q0VBL1, Q17QR8, Q17RP2, Q3V1F8, Q4W5G0, Q5U538, Q5XH12, Q60976, Q62711, Q66KB7, Q6AZB8, Q6B0B8, Q6IE26, Q6NT04, Q6P7F1, Q7L775, Q7L7V1, Q7TM95, Q8BR93, Q8BUZ3, Q8BZS9, Q8IY51, Q8K3R3, Q8VEH5, Q924H9, Q94K49, Q96DM1

Diamond homologs: B2RD01, B2RRL2, O75564, Q0VBL1, Q4W5G0, Q60976, Q6NT04, Q9Y4A0, Q96MW7, B1WC39, Q499M4, Q17RP2, Q8BUZ3, G3MY25, Q53EQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	14
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

688 predictions. Top by Δscore:

Variant	Effect	Δscore
8:142681324:CA:C	acceptor_loss	1.0000
8:142681435:G:GG	donor_gain	1.0000
8:142681461:GCC:G	donor_gain	1.0000
8:142664472:CCTCA:C	donor_loss	0.9900
8:142664473:CTCAC:C	donor_loss	0.9900
8:142664474:TCA:T	donor_loss	0.9900
8:142664475:CA:C	donor_loss	0.9900
8:142664476:A:C	donor_loss	0.9900
8:142664477:C:CA	donor_loss	0.9900
8:142664477:CCTG:C	donor_gain	0.9900
8:142664527:T:TA	donor_gain	0.9900
8:142664788:T:TA	donor_gain	0.9900
8:142680559:GCCAG:G	donor_gain	0.9900
8:142680561:CAGG:C	donor_loss	0.9900
8:142680562:AGG:A	donor_loss	0.9900
8:142680563:GGTGA:G	donor_loss	0.9900
8:142680564:G:GA	donor_loss	0.9900
8:142681325:A:AG	acceptor_gain	0.9900
8:142681325:AG:A	acceptor_gain	0.9900
8:142681326:G:GT	acceptor_gain	0.9900
8:142681326:GG:G	acceptor_gain	0.9900
8:142681326:GGC:G	acceptor_gain	0.9900
8:142681326:GGCA:G	acceptor_gain	0.9900
8:142681326:GGCAC:G	acceptor_gain	0.9900
8:142681409:G:T	donor_gain	0.9900
8:142681432:TCC:T	donor_gain	0.9900
8:142681409:G:GT	donor_gain	0.9800
8:142681433:CC:C	donor_gain	0.9800
8:142681915:CCCCA:C	acceptor_loss	0.9800
8:142681918:CAG:C	acceptor_loss	0.9800

AlphaMissense

3713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142665642:A:C	F139L	0.999
8:142665642:A:T	F139L	0.999
8:142665643:A:G	F139S	0.999
8:142665644:A:G	F139L	0.999
8:142665656:A:G	W135R	0.999
8:142665656:A:T	W135R	0.999
8:142665666:G:C	F131L	0.999
8:142665666:G:T	F131L	0.999
8:142665668:A:G	F131L	0.999
8:142665632:G:C	H143D	0.998
8:142665639:C:A	K140N	0.998
8:142665639:C:G	K140N	0.998
8:142665654:C:A	W135C	0.998
8:142665654:C:G	W135C	0.998
8:142665667:A:G	F131S	0.998
8:142665713:C:G	A116P	0.998
8:142665724:A:T	L112H	0.998
8:142665724:A:G	L112P	0.997
8:142665919:A:T	V47E	0.997
8:142665633:T:A	R142S	0.996
8:142665633:T:G	R142S	0.996
8:142665634:C:G	R142T	0.996
8:142665643:A:C	F139C	0.996
8:142665658:C:T	G134E	0.996
8:142665664:G:A	S132F	0.996
8:142665712:G:T	A116D	0.996
8:142665652:A:G	L136P	0.995
8:142665668:A:T	F131I	0.995
8:142665897:G:C	D54E	0.995
8:142665897:G:T	D54E	0.995

dbSNP variants (sampled 300 via entrez): RS1000028328 (8:142661012 C>A), RS1000042157 (8:142663598 C>G,T), RS1000081743 (8:142661207 G>A,C), RS1000432315 (8:142669360 C>A,T), RS1000484877 (8:142669533 G>A,C), RS1000714180 (8:142665322 C>T), RS1000764061 (8:142668250 G>C), RS1000816882 (8:142668456 T>C), RS1001200136 (8:142661962 G>A,C), RS1001211384 (8:142666035 C>A), RS1001402397 (8:142643446 C>T), RS1001442316 (8:142670742 T>C), RS1001757055 (8:142646207 A>G), RS1002002233 (8:142645356 T>C), RS1002196279 (8:142650706 T>G)

Disease associations

OMIM: gene MIM:603210 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000020	Urinary incontinence
HP:0000153	Abnormality of the mouth
HP:0000496	Abnormality of eye movement
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001328	Specific learning disability
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002133	Status epilepticus
HP:0002197	Generalized-onset seizure
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002392	EEG with polyspike wave complexes
HP:0002883	Hyperventilation
HP:0006961	Jerky head movements
HP:0007000	Morning myoclonic jerks
HP:0007018	Attention deficit hyperactivity disorder
HP:0007207	Photosensitive tonic-clonic seizure
HP:0007738	Uncontrolled eye movements
HP:0010522	Dyslexia
HP:0010794	Impaired visuospatial constructive cognition
HP:0010848	EEG with spike-wave complexes (2.5-3.5 Hz)
HP:0011147	Typical absence seizure
HP:0011150	Myoclonic absence seizure
HP:0012433	Abnormal social behavior
HP:0030218	Punding
HP:0031469	Low self-esteem
HP:0045084	Limb myoclonus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005012_24	Urinary tract infection frequency	3.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Ozone	increases oxidation, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
hydroquinone	decreases expression	1
avobenzone	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	affects expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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