RIPPLY1

Summary

RIPPLY1 (ripply transcriptional repressor 1, HGNC:25117) is a protein-coding gene on chromosome Xq22.3, encoding Protein ripply1 (Q0D2K3). Plays a role in somitogenesis.

This gene encodes a protein similar to a zebrafish protein which acts as a transcriptional repressor in and is required for somite segmentation in zebrafish embryos (PMID: 16326386). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 92129 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebellar ataxia, intellectual disability, and dysequilibrium (Limited, GenCC)
• GWAS associations: 2
• MANE Select transcript: NM_138382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25117
Approved symbol	RIPPLY1
Name	ripply transcriptional repressor 1
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147223
Ensembl biotype	protein_coding
OMIM	300575
Entrez	92129

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000276173, ENST00000411805

RefSeq mRNA: 2 — MANE Select: NM_138382 NM_001171706, NM_138382

CCDS: CCDS48145, CCDS55471

Canonical transcript exons

ENST00000276173 — 4 exons

Exon	Start	End
ENSE00000979259	106902140	106902215
ENSE00000979260	106901474	106901538
ENSE00001670749	106900063	106900908
ENSE00001692152	106903133	106903341

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 83.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1407 / max 81.2361, expressed in 24 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200043	0.1224	24
200044	0.0183	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.35	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.27	gold quality
right lobe of liver	UBERON:0001114	73.31	gold quality
liver	UBERON:0002107	62.87	gold quality
metanephros cortex	UBERON:0010533	60.42	gold quality
adult mammalian kidney	UBERON:0000082	59.83	gold quality
right adrenal gland	UBERON:0001233	58.58	gold quality
right adrenal gland cortex	UBERON:0035827	57.46	gold quality
left adrenal gland	UBERON:0001234	57.23	gold quality
left adrenal gland cortex	UBERON:0035825	56.22	gold quality
adrenal cortex	UBERON:0001235	55.34	gold quality
metanephros	UBERON:0000081	54.46	gold quality
kidney	UBERON:0002113	53.65	gold quality
adrenal gland	UBERON:0002369	53.39	gold quality
lower lobe of lung	UBERON:0008949	52.99	silver quality
cerebellar vermis	UBERON:0004720	52.19	gold quality
cortex of kidney	UBERON:0001225	50.00	gold quality
mucosa of stomach	UBERON:0001199	48.03	gold quality
mucosa of transverse colon	UBERON:0004991	47.21	gold quality
gastrocnemius	UBERON:0001388	44.94	gold quality
muscle of leg	UBERON:0001383	44.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.76	gold quality
middle temporal gyrus	UBERON:0002771	44.53	gold quality
islet of Langerhans	UBERON:0000006	44.43	gold quality
left uterine tube	UBERON:0001303	43.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
inferior vagus X ganglion	UBERON:0005363	42.92	gold quality
sural nerve	UBERON:0015488	42.76	gold quality
trachea	UBERON:0003126	42.72	gold quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting RIPPLY1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-3200-3P	95.41	64.23	396
HSA-MIR-5191	95.22	64.69	354

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ripply2	ENSDARG00000070535
mus_musculus	Ripply1	ENSMUSG00000072945
rattus_norvegicus	Ripply1	ENSRNOG00000061101

Paralogs (2): RIPPLY3 (ENSG00000183145), RIPPLY2 (ENSG00000203877)

Protein

Protein identifiers

Protein ripply1 — Q0D2K3 (reviewed: Q0D2K3)

All UniProt accessions (1): Q0D2K3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in somitogenesis. Essential for transcriptional repression of the segmental patterning genes, thus terminating the segmentation program in the presomitic mesoderm, and also required for the maintenance of rostrocaudal polarity in somites.

Subcellular location. Nucleus.

Domain organisation. The ripply homology domain is required for transcriptional repression. The WRPW motif is required for binding to TLE/GROUCHO proteins.

Similarity. Belongs to the ripply family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q0D2K3-1	1	yes
Q0D2K3-2	2

RefSeq proteins (2): NP_001165177, NP_612391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028127	Ripply_fam	Family

Pfam: PF14998

UniProt features (6 total): region of interest 2, chain 1, short sequence motif 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0D2K3-F1	61.12	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_EMBRYONIC_PATTERN_SPECIFICATION, GOBP_SOMITOGENESIS, GOBP_SEGMENTATION, GOBP_SEGMENT_SPECIFICATION, GOBP_ANTERIOR_POSTERIOR_AXIS_SPECIFICATION, GOBP_EMBRYO_DEVELOPMENT, MODULE_95, GOBP_SOMITE_DEVELOPMENT, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, chrXq22

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), somite specification (GO:0001757), embryonic pattern specification (GO:0009880), somite rostral/caudal axis specification (GO:0032525), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
somitogenesis	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
segment specification	1
embryonic pattern specification	1
pattern specification process	1
embryo development	1
embryonic axis specification	1
anterior/posterior axis specification	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIPPLY1	MESP2	Q0VG99	695
RIPPLY1	TBX6	O95947	615
RIPPLY1	UNCX	A6NJT0	509
RIPPLY1	CCDC40	Q4G0X9	444
RIPPLY1	LMX1B	O60663	433
RIPPLY1	MSGN1	A6NI15	422
RIPPLY1	SOBP	A7XYQ1	409
RIPPLY1	MEOX1	P50221	402
RIPPLY1	SEMA7A	O75326	398
RIPPLY1	TBC1D8B	Q0IIM8	398
RIPPLY1	MORC4	Q8TE76	391
RIPPLY1	ETNK2	Q9NVF9	386
RIPPLY1	MYMX	A0A1B0GTQ4	384
RIPPLY1	PBX4	Q9BYU1	378
RIPPLY1	CHRNA4	P43681	349

IntAct

147 interactions, top by confidence:

A	B	Type	Score
TRAF2	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.720
RIPPLY1	MDFI	psi-mi:“MI:0915”(physical association)	0.720
RIPPLY1	THAP1	psi-mi:“MI:0915”(physical association)	0.720
MDFI	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.720
THAP1	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.720
RIPPLY1	TRAF2	psi-mi:“MI:0915”(physical association)	0.720
RIPPLY1	REL	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.560
HDAC7	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
REL	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	HDAC7	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	MCCD1	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	MED19	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	PTTG2	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	IRAK1BP1	psi-mi:“MI:0915”(physical association)	0.560
KRT34	RIPPLY1	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	TRAF3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (64): RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid), TLE4 (Affinity Capture-MS), TLE2 (Affinity Capture-MS), TLE1 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), AES (Affinity Capture-MS), CHMP6 (Affinity Capture-MS), RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid), RIPPLY1 (Two-hybrid)

ESM2 similar proteins: A2AIW0, A4IH95, A5D8S8, A6NMK8, A6QLA6, A9JRX0, B1H3B4, B2GUZ2, B7SXM5, B7XDF1, F1R983, F7BHS0, P0DPK0, P46414, P46529, Q0D2K3, Q0IHW6, Q13111, Q25QX6, Q2WG77, Q2WG78, Q2WG79, Q2WG80, Q4V7W3, Q503Y8, Q52KN3, Q5I2D0, Q5M9G5, Q60439, Q66KC9, Q673G8, Q68DK7, Q6DF94, Q6GQV1, Q6NRH7, Q6NRK3, Q6PB51, Q6PDM1, Q6QZN6, Q76N89

Diamond homologs: B1H3B4, B7XDF1, P57055, Q0D2K3, Q25QX6, Q2WG76, Q2WG77, Q2WG78, Q2WG79, Q2WG80, Q5I2D0, Q5TAB7, Q8QGU6, Q924S9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

798 predictions. Top by Δscore:

Variant	Effect	Δscore
X:106900328:G:GT	donor_gain	0.9900
X:106900907:GC:G	acceptor_gain	0.9900
X:106900907:GCCTG:G	acceptor_loss	0.9900
X:106900908:CC:C	acceptor_gain	0.9900
X:106900908:CCTG:C	acceptor_loss	0.9900
X:106900909:C:CC	acceptor_gain	0.9900
X:106900910:T:G	acceptor_loss	0.9900
X:106902598:T:TA	donor_gain	0.9900
X:106903129:TTAC:T	donor_loss	0.9800
X:106903130:TA:T	donor_loss	0.9800
X:106903131:A:AC	donor_gain	0.9800
X:106903131:A:T	donor_loss	0.9800
X:106903132:C:CC	donor_gain	0.9800
X:106903132:C:CG	donor_loss	0.9800
X:106903132:CCTTT:C	donor_gain	0.9800
X:106900905:GAGC:G	acceptor_gain	0.9700
X:106903151:T:TA	donor_gain	0.9700
X:106901602:C:CC	acceptor_gain	0.9600
X:106902216:C:CC	acceptor_gain	0.9600
X:106900904:AGAGC:A	acceptor_gain	0.9500
X:106900906:AGC:A	acceptor_gain	0.9500
X:106902214:CT:C	acceptor_gain	0.9500
X:106902211:TTCCT:T	acceptor_gain	0.9400
X:106902636:T:TA	donor_gain	0.9400
X:106902694:T:C	acceptor_gain	0.9400
X:106903131:AC:A	donor_gain	0.9400
X:106903132:CC:C	donor_gain	0.9400
X:106901467:AGCTT:A	donor_loss	0.9300
X:106901468:GCTT:G	donor_loss	0.9300
X:106901469:CTTAC:C	donor_loss	0.9300

AlphaMissense

973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:106900822:A:C	I128S	0.991
X:106900822:A:T	I128N	0.991
X:106900822:A:G	I128T	0.989
X:106900834:A:T	V124D	0.987
X:106900829:C:G	A126P	0.986
X:106900852:A:G	L118S	0.985
X:106901477:A:T	V98D	0.985
X:106900849:A:G	L119P	0.983
X:106900901:A:G	W102R	0.982
X:106900901:A:T	W102R	0.982
X:106901488:G:C	F94L	0.982
X:106901488:G:T	F94L	0.982
X:106901490:A:G	F94L	0.982
X:106900840:A:G	F122S	0.977
X:106901482:G:C	H96Q	0.975
X:106901482:G:T	H96Q	0.975
X:106902197:C:A	R58S	0.974
X:106902197:C:G	R58S	0.974
X:106902193:A:G	W60R	0.973
X:106902193:A:T	W60R	0.973
X:106900830:C:A	Q125H	0.972
X:106900830:C:G	Q125H	0.972
X:106900899:C:A	W102C	0.971
X:106900899:C:G	W102C	0.971
X:106900906:A:G	L100P	0.968
X:106901484:G:C	H96D	0.968
X:106900828:G:T	A126E	0.966
X:106900908:C:A	R99S	0.965
X:106900908:C:G	R99S	0.965
X:106900849:A:T	L119Q	0.964

dbSNP variants (sampled 300 via entrez): RS1000070618 (X:106904302 C>T), RS1000505782 (X:106903857 G>A,T), RS1001571426 (X:106904892 G>A), RS1001587558 (X:106901658 G>T), RS1002208261 (X:106903950 T>C), RS1004719838 (X:106901768 A>C,T), RS1005120837 (X:106901085 C>T), RS1005848617 (X:106903045 C>T), RS1006194310 (X:106899947 A>C,G), RS1007273937 (X:106904242 C>T), RS1007308164 (X:106903727 G>A), RS1008747041 (X:106902978 T>G), RS1009829631 (X:106903867 G>A), RS1010626782 (X:106900246 G>T), RS1011661890 (X:106901538 C>A,T)

Disease associations

OMIM: gene MIM:300575 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebellar ataxia, intellectual disability, and dysequilibrium	Limited	Autosomal recessive

Mondo (1): cerebellar ataxia, intellectual disability, and dysequilibrium (MONDO:0009133)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001741_2	Pancreatitis	2.000000e-22
GCST004860_73	Alcoholic chronic pancreatitis	2.000000e-29

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535731	Dysequilibrium syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
N(4)-hydroxycytidine	decreases expression	1
trichostatin A	decreases 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	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06366230	PHASE1/PHASE2	RECRUITING	Adding Urea to the Final Dialysis Fluid