Riddle Syndrome disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

RIDL MCID: RDD003 MIFTS: 49	Riddle Syndrome (RIDL) Categories: Blood diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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Aliases & Classifications for Riddle Syndrome

MalaCards integrated aliases for Riddle Syndrome:

Name: Riddle Syndrome ⁵⁶ ¹² ⁵⁸ ⁷³ ³⁶ ²⁹ ¹³ ⁶ ⁴³ ¹⁵ ³⁹ ¹⁷ ⁷¹

Radiosensitivity-Immunodeficiency-Dysmorphic Features-Learning Difficulties Syndrome ¹² ⁵⁸

Rnf168 Deficiency ¹² ⁵⁸

Radiosensitivity, Immunodeficiency, Dysmorphic Facial Features, and Learning Difficulties ⁵⁶

Riddles ⁷³

Ridl ⁵⁶

Characteristics:

Orphanet epidemiological data:

⁵⁸

riddle syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Infancy; Age of death: adult;

OMIM:

⁵⁶

Inheritance:
autosomal recessive

Miscellaneous:
two unrelated patients have been reported (last curated july 2014) onset in infancy or childhood

HPO:

³¹

riddle syndrome:
Inheritance autosomal recessive inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Neuronal diseases Blood diseases Immune diseases

See all MalaCards categories (disease lists)

ICD10: ³² ³³

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Certain disorders involving the immune mechanism

Immunodeficiency associated with other major defects

Immunodeficiency associated with other specified major defects

Orphanet: ⁵⁸

Rare neurological diseases

Rare immunological diseases

External Ids:

Disease Ontology ¹² DOID:0090113

OMIM ⁵⁶ 611943

KEGG ³⁶ H00962

MeSH ⁴³ C567453

ICD10 ³² D82.8

ICD10 via Orphanet ³³ D82.8

UMLS via Orphanet ⁷² C2677792

Orphanet ⁵⁸ ORPHA420741

MedGen ⁴¹ C2677792

EFO ¹⁷ EFO_0009055

UMLS ⁷¹ C2677792

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Summaries for Riddle Syndrome

KEGG : ³⁶ RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties) syndrome is an immunodeficiency disorder that primarily manifests as an immunoglobulin deficiency. The underlying genetic cause of this syndrome is defective RNF168 that functions to recruit DNA double-strand break (DSB) repair proteins, such as 53BP1 and BRCA1, to sites of DNA damage. As with patients with other DSB repair disorders, the RIDDLE patients also present with nonimmunological characteristics including short stature and motor control problems.

MalaCards based summary : Riddle Syndrome, also known as radiosensitivity-immunodeficiency-dysmorphic features-learning difficulties syndrome, is related to ataxia-telangiectasia and canavan disease, and has symptoms including ataxia and dry skin. An important gene associated with Riddle Syndrome is RNF168 (Ring Finger Protein 168), and among its related pathways/superpathways are Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 and Metabolism of proteins. Affiliated tissues include skin, eye and breast, and related phenotypes are short stature and immunodeficiency

Disease Ontology : ¹² A syndrome that is characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature, and that has material basis in homozygous or compound heterozygous mutation in the ring finger protein 168 (RNF168) gene on chromosome 3q29.

OMIM : ⁵⁶ RIDDLE is an acronym for the major features of this syndrome: radiosensitivity, immunodeficiency, dysmorphic facies, and learning difficulties (Stewart et al., 2007). (611943)

UniProtKB/Swiss-Prot : ⁷³ Riddle syndrome: Characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions.

Wikipedia : ⁷⁴ RIDDLE syndrome is a rare genetic syndrome. The name is an acronym for Radiosensitivity,... more...

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Related Diseases for Riddle Syndrome

Diseases related to Riddle Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 284)

#	Related Disease	Score	Top Affiliating Genes
1	ataxia-telangiectasia	29.5	TP53BP1 H2AX BRCA1
2	canavan disease	11.3
3	ovarian carcinosarcoma	10.2	H2AC18 BRCA1
4	breast cancer	10.2
5	legionnaire disease	10.2
6	lung large cell carcinoma	10.2
7	hypoglycemia	10.2
8	candida glabrata	10.2
9	sarcoidosis 1	10.1
10	primary agammaglobulinemia	10.1
11	aplastic anemia	10.1
12	pulmonary fibrosis and/or bone marrow failure, telomere-related, 2	10.1
13	atrial fibrillation	10.1
14	primary hyperoxaluria	10.0	TP53BP1 H2AC20 H2AC18
15	severe combined immunodeficiency with sensitivity to ionizing radiation	10.0	TP53BP1 H2AC18 ERCC6
16	pfeiffer syndrome	10.0
17	autism	10.0
18	malaria	10.0
19	tropical sprue	10.0
20	diarrhea	10.0
21	cholera	10.0
22	pustulosis of palm and sole	10.0
23	psoriasis	10.0
24	depression	10.0
25	fanconi anemia, complementation group d1	10.0	H2AC18 ERCC6 BRCA1
26	fanconi anemia, complementation group j	10.0	H2AC18 ERCC6 BRCA1
27	wilson-turner x-linked mental retardation syndrome	10.0	H2AC18 H2AC13 H2AC12
28	immune deficiency disease	9.9
29	syndromic x-linked intellectual disability	9.9	H2AC18 H2AC13 H2AC12
30	lig4 syndrome	9.9	TP53BP1 RNF168 MDC1
31	cockayne syndrome b	9.9	ERCC6 BRCA1
32	xeroderma pigmentosum group e	9.9	H2AC20 H2AC18 ERCC6
33	alzheimer disease	9.9
34	atherosclerosis susceptibility	9.9
35	gastroesophageal reflux	9.9
36	osteoporosis	9.9
37	otitis media	9.9
38	parkinson disease, late-onset	9.9
39	prostate cancer	9.9
40	syringomyelia, noncommunicating isolated	9.9
41	anemia, x-linked, with or without neutropenia and/or platelet abnormalities	9.9
42	asthma	9.9
43	bone mineral density quantitative trait locus 8	9.9
44	acute promyelocytic leukemia	9.9
45	bone mineral density quantitative trait locus 15	9.9
46	deficiency anemia	9.9
47	aphasia	9.9
48	thrombosis	9.9
49	exhibitionism	9.9
50	amnestic disorder	9.9

Graphical network of the top 20 diseases related to Riddle Syndrome:

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Symptoms & Phenotypes for Riddle Syndrome

Human phenotypes related to Riddle Syndrome:

⁵⁸ ³¹ (show all 46)

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	short stature ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0004322
2	immunodeficiency ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0002721
3	elevated alpha-fetoprotein ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0006254
4	decreased circulating iga level ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0002720
5	decreased circulating igg level ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0004315
6	chromosomal breakage induced by ionizing radiation ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0010997
7	abnormal facial shape ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0001999
8	specific learning disability ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0001328
9	recurrent pneumonia ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0006532
10	recurrent fever ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0001954
11	bronchitis ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0012387
12	recurrent sinusitis ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0011108
13	chronic sinusitis ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0011109
14	global developmental delay ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001263
15	arthritis ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001369
16	microcephaly ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000252
17	gait disturbance ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001288
18	ataxia ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001251
19	weight loss ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001824
20	erythema ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0010783
21	abdominal pain ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002027
22	restrictive ventilatory defect ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002091
23	pulmonary fibrosis ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002206
24	conjunctival telangiectasia ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000524
25	otitis media ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000388
26	headache ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002315
27	respiratory failure ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002878
28	clumsiness ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002312
29	emotional lability ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000712
30	diarrhea ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002014
31	interstitial pulmonary abnormality ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0006530
32	abnormality of the cerebral white matter ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002500
33	demyelinating peripheral neuropathy ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0007108
34	decreased circulating total igm ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002850
35	generalized lymphadenopathy ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0008940
36	scaling skin ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0040189
37	recurrent viral infections ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0004429
38	neonatal asphyxia ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0012768
39	enuresis nocturna ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0010677
40	poor hand-eye coordination ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0007057
41	intraventricular hemorrhage ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0030746
42	dry skin ³¹			HP:0000958
43	mild global developmental delay ³¹			HP:0011342
44	pneumonia ⁵⁸		Frequent (79-30%)
45	telangiectasia ⁵⁸		Occasional (29-5%)
46	increased sensitivity to ionizing radiation ³¹			HP:0011133

Symptoms via clinical synopsis from OMIM:

⁵⁶

Growth Height:
short stature

Neurologic Central Nervous System:
ataxia
learning difficulties (in 1 patient)
impaired motor control, mild

Head And Neck Head:
microcephaly (in some patients)

Head And Neck Eyes:
ocular telangiectasia

Immunology:
immunodeficiency
variably decreased serum iga, igg, and igm

Skin Nails Hair Skin:
dry skin

Laboratory Abnormalities:
increased alpha-fetoprotein
cells show increased sensitivity to ionizing radiation
defect in double-stranded dna repair

Respiratory:
progressive pulmonary failure (1 patient)
interstitial pneumonia (1 patient)
pulmonary fibrosis (1 patient)
bronchial telangiectasia (1 patient)

Clinical features from OMIM:

611943

UMLS symptoms related to Riddle Syndrome:

ataxia, dry skin

GenomeRNAi Phenotypes related to Riddle Syndrome according to GeneCards Suite gene sharing:

²⁶ (show top 50) (show all 80)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased shRNA abundance (Z-score < -2)	GR00366-A-100	10.88	H2AC15
2	Decreased shRNA abundance (Z-score < -2)	GR00366-A-105	10.88	H2AC18 H2AC20
3	Decreased shRNA abundance (Z-score < -2)	GR00366-A-116	10.88	H2AC15
4	Decreased shRNA abundance (Z-score < -2)	GR00366-A-118	10.88	H2AC11
5	Decreased shRNA abundance (Z-score < -2)	GR00366-A-119	10.88	H2AC15
6	Decreased shRNA abundance (Z-score < -2)	GR00366-A-123	10.88	BRCC3
7	Decreased shRNA abundance (Z-score < -2)	GR00366-A-136	10.88	BRCC3
8	Decreased shRNA abundance (Z-score < -2)	GR00366-A-137	10.88	H2AC15
9	Decreased shRNA abundance (Z-score < -2)	GR00366-A-139	10.88	H2AC18 H2AC20 H2AC13
10	Decreased shRNA abundance (Z-score < -2)	GR00366-A-165	10.88	H2AC18 H2AC20 H2AC13
11	Decreased shRNA abundance (Z-score < -2)	GR00366-A-168	10.88	H2AC18 H2AC20
12	Decreased shRNA abundance (Z-score < -2)	GR00366-A-173	10.88	H2AC20
13	Decreased shRNA abundance (Z-score < -2)	GR00366-A-174	10.88	H2AC12
14	Decreased shRNA abundance (Z-score < -2)	GR00366-A-195	10.88	H2AC11 H2AC12
15	Decreased shRNA abundance (Z-score < -2)	GR00366-A-216	10.88	H2AC15 H2AC18 H2AC20
16	Decreased shRNA abundance (Z-score < -2)	GR00366-A-27	10.88	H2AC11
17	Decreased shRNA abundance (Z-score < -2)	GR00366-A-34	10.88	H2AC15 MDC1 H2AX
18	Decreased shRNA abundance (Z-score < -2)	GR00366-A-40	10.88	H2AC11 H2AC12 H2AC15 H2AC18 H2AC20
19	Decreased shRNA abundance (Z-score < -2)	GR00366-A-42	10.88	H2AC15
20	Decreased shRNA abundance (Z-score < -2)	GR00366-A-43	10.88	H2AC12 H2AC18 H2AC20 H2AX
21	Decreased shRNA abundance (Z-score < -2)	GR00366-A-46	10.88	H2AC13
22	Decreased shRNA abundance (Z-score < -2)	GR00366-A-60	10.88	H2AC15
23	Decreased shRNA abundance (Z-score < -2)	GR00366-A-7	10.88	MDC1
24	Decreased shRNA abundance (Z-score < -2)	GR00366-A-77	10.88	H2AC13
25	Decreased shRNA abundance (Z-score < -2)	GR00366-A-81	10.88	H2AC12
26	Decreased shRNA abundance (Z-score < -2)	GR00366-A-91	10.88	H2AC13 H2AX
27	Decreased shRNA abundance (Z-score < -2)	GR00366-A-99	10.88	BRCC3
28	Increased shRNA abundance (Z-score > 2)	GR00366-A-10	10.88	H2AC13
29	Increased shRNA abundance (Z-score > 2)	GR00366-A-106	10.88	H2AC13
30	Increased shRNA abundance (Z-score > 2)	GR00366-A-11	10.88	TP53BP1
31	Increased shRNA abundance (Z-score > 2)	GR00366-A-112	10.88	MDC1
32	Increased shRNA abundance (Z-score > 2)	GR00366-A-115	10.88	ERCC6
33	Increased shRNA abundance (Z-score > 2)	GR00366-A-119	10.88	H2AC15 H2AC13 H2AC20
34	Increased shRNA abundance (Z-score > 2)	GR00366-A-12	10.88	H2AC15 ERCC6
35	Increased shRNA abundance (Z-score > 2)	GR00366-A-121	10.88	RNF168
36	Increased shRNA abundance (Z-score > 2)	GR00366-A-125	10.88	H2AC13
37	Increased shRNA abundance (Z-score > 2)	GR00366-A-13	10.88	H2AC15
38	Increased shRNA abundance (Z-score > 2)	GR00366-A-132	10.88	H2AC13 ERCC6
39	Increased shRNA abundance (Z-score > 2)	GR00366-A-137	10.88	MDC1 BRCA1 ERCC6
40	Increased shRNA abundance (Z-score > 2)	GR00366-A-139	10.88	BRCA1
41	Increased shRNA abundance (Z-score > 2)	GR00366-A-148	10.88	H2AX ERCC6
42	Increased shRNA abundance (Z-score > 2)	GR00366-A-150	10.88	MDC1
43	Increased shRNA abundance (Z-score > 2)	GR00366-A-152	10.88	H2AC15 H2AC20
44	Increased shRNA abundance (Z-score > 2)	GR00366-A-16	10.88	ERCC6
45	Increased shRNA abundance (Z-score > 2)	GR00366-A-160	10.88	H2AC15
46	Increased shRNA abundance (Z-score > 2)	GR00366-A-164	10.88	ERCC6
47	Increased shRNA abundance (Z-score > 2)	GR00366-A-168	10.88	RNF168 TP53BP1 BRCA1
48	Increased shRNA abundance (Z-score > 2)	GR00366-A-169	10.88	H2AC20
49	Increased shRNA abundance (Z-score > 2)	GR00366-A-179	10.88	H2AC12
50	Increased shRNA abundance (Z-score > 2)	GR00366-A-185	10.88	TP53BP1

MGI Mouse Phenotypes related to Riddle Syndrome:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	neoplasm	MP:0002006	9.17	BRCA1 ERCC6 H2AX RNF168 RNF8 TP53BP1

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Drugs & Therapeutics for Riddle Syndrome

Search Clinical Trials , NIH Clinical Center for Riddle Syndrome

Cochrane evidence based reviews: riddle syndrome

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Genetic Tests for Riddle Syndrome

Genetic tests related to Riddle Syndrome:

#	Genetic test	Affiliating Genes
1	Riddle Syndrome ²⁹	RNF168

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Anatomical Context for Riddle Syndrome

MalaCards organs/tissues related to Riddle Syndrome:

⁴⁰

Skin, Eye, Breast

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Publications for Riddle Syndrome

Articles related to Riddle Syndrome:

(show all 13)

#	Title	Authors	PMID	Year
1	The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. ⁶¹ ⁵⁶ ⁶	Stewart GS...Durocher D	19203578	2009
2	Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia. ⁶ ⁵⁶	Devgan SS...Gatti RA	21394101	2011
3	RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling. ⁵⁶ ⁶¹	Stewart GS...Taylor AM	17940005	2007
4	Novel 3q27.2-qter deletion in a patient with Diamond-Blackfan anemia and immunodeficiency: Case report and review of literature. ⁶¹	Alkhunaizi E...Braverman N	28432740	2017
5	Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility. ⁶¹	Mantere T...Pylkas K	28386063	2017
6	An E2-guided E3 Screen Identifies the RNF17-UBE2U Pair as Regulator of the Radiosensitivity, Immunodeficiency, Dysmorphic Features, and Learning Difficulties (RIDDLE) Syndrome Protein RNF168. ⁶¹	Guo Y...Huen MS	27903633	2017
7	Clinical and Biological Manifestation of RNF168 Deficiency in Two Polish Siblings. ⁶¹	Pietrucha B...Dork T	29255463	2017
8	RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation. ⁶¹	Guturi KKN...Hakem R	27558965	2016
9	Modulation of LSD1 phosphorylation by CK2/WIP1 regulates RNF168-dependent 53BP1 recruitment in response to DNA damage. ⁶¹	Peng B...Xu X	25999347	2015
10	The 3q29 microdeletion syndrome: report of three new unrelated patients and in silico "RNA binding" analysis of the 3q29 region. ⁶¹	Dasouki MJ...Gorre M	21626679	2011
11	Genomic instability, defective spermatogenesis, immunodeficiency, and cancer in a mouse model of the RIDDLE syndrome. ⁶¹	Bohgaki T...Hakem R	21552324	2011
12	DNA double-strand break repair, immunodeficiency and the RIDDLE syndrome. ⁶¹	Blundred RM...Stewart GS	21426255	2011
13	Solving the RIDDLE of 53BP1 recruitment to sites of damage. ⁶¹	Stewart GS	19372751	2009

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Genes for Riddle Syndrome

Genes related to Riddle Syndrome (1 elite genes):

(show all 18)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	RNF168	Ring Finger Protein 168	Protein Coding	1394.13	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative germline mutation ⁵⁸ Genetic Tests ²⁹ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Publications Summaries Variants (show sections)	21394101 19203578
2	H2AC18	H2A Clustered Histone 18	Protein Coding	19.77	DISEASES inferred ¹⁵ ¹⁵ GeneCards inferred via : Publications (show sections)
3	RNF8	Ring Finger Protein 8	Protein Coding	14.48	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
4	TP53BP1	Tumor Protein P53 Binding Protein 1	Protein Coding	14.17	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
5	UBE2N	Ubiquitin Conjugating Enzyme E2 N	Protein Coding	13.56	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
6	H2AC20	H2A Clustered Histone 20	Protein Coding	12.99	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
7	BRCA1	BRCA1 DNA Repair Associated	Protein Coding	12.9	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
8	H2AX	H2A.X Variant Histone	Protein Coding	11.25	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
9	ERCC6	ERCC Excision Repair 6, Chromatin Remodeling Factor	Protein Coding	8.63	DISEASES inferred ¹⁵ ¹⁵
10	MDC1	Mediator Of DNA Damage Checkpoint 1	Protein Coding	7.39	DISEASES inferred ¹⁵
11	UIMC1	Ubiquitin Interaction Motif Containing 1	Protein Coding	7.07	DISEASES inferred ¹⁵
12	BRCC3	BRCA1/BRCA2-Containing Complex Subunit 3	Protein Coding	6.79	DISEASES inferred ¹⁵
13	H2AC1	H2A Clustered Histone 1	Protein Coding	6.21	GeneCards inferred via : Publications (show sections)
14	H2AC11	H2A Clustered Histone 11	Protein Coding	6.21	GeneCards inferred via : Publications (show sections)
15	H2AC12	H2A Clustered Histone 12	Protein Coding	6.21	GeneCards inferred via : Publications (show sections)
16	H2AC13	H2A Clustered Histone 13	Protein Coding	6.21	GeneCards inferred via : Publications (show sections)
17	H2AC14	H2A Clustered Histone 14	Protein Coding	6.21	GeneCards inferred via : Publications (show sections)
18	H2AC15	H2A Clustered Histone 15	Protein Coding	6.21	GeneCards inferred via : Publications (show sections)

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Variations for Riddle Syndrome

ClinVar genetic disease variations for Riddle Syndrome:

⁶ ‎‎ ‎‎ ‎‎

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	RNF168	NM_152617.4(RNF168):c.1323_1326del (p.Gln442fs)	deletion	Pathogenic	488		3:196199080-196199083	3:196472209-196472212
2	RNF168	NM_152617.4(RNF168):c.397dup (p.Ala133fs)	duplication	Pathogenic	487		3:196214430-196214431	3:196487559-196487560
3	RNF168	NM_152617.4(RNF168):c.391C>T (p.Arg131Ter)	SNV	Likely pathogenic	140755	rs201915239	3:196214437-196214437	3:196487566-196487566

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Expression for Riddle Syndrome

Search GEO for disease gene expression data for Riddle Syndrome.

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Pathways for Riddle Syndrome

Pathways related to Riddle Syndrome according to GeneCards Suite gene sharing:

(show all 18)

#	Super pathways	Score	Top Affiliating Genes
1	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 ⁶⁵ Show member pathways Activation of anterior HOX genes in hindbrain development during early embryogenesis ⁶⁵ Activation of HOX genes during differentiation ⁶⁵ Alcoholism ³⁶ Amyloid fiber formation ⁶⁵ B-WICH complex positively regulates rRNA expression ⁶⁵ Condensation of Prophase Chromosomes ⁶⁵ DNA methylation ⁶⁵ Epigenetic regulation of gene expression ⁶⁵ ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression ⁶⁵ Formation of the beta-catenin-TCF transactivating complex ⁶⁵ HDACs deacetylate histones ⁶⁵ HDMs demethylate histones ⁶⁵ Negative epigenetic regulation of rRNA expression ⁶⁵ NoRC negatively regulates rRNA expression ⁶⁵ Positive epigenetic regulation of rRNA expression ⁶⁵ PRC2 methylates histones and DNA ⁶⁵ RHO GTPases activate PKNs ⁶⁵ RMTs methylate histone arginines ⁶⁵ RNA Polymerase I Chain Elongation ⁶⁵ RNA Polymerase I Promoter Clearance ⁶⁵ RNA Polymerase I Promoter Opening ⁶⁵ RNA Polymerase I Transcription ⁶⁵ RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription ⁶⁵ SIRT1 negatively regulates rRNA Expression ⁶⁵ Systemic lupus erythematosus ³⁶	13.67	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
2	Metabolism of proteins ⁶⁵ Show member pathways Post-translational protein modification ⁶⁵	13.65	UIMC1 UBE2N TP53BP1 RNF168 MDC1 H2AX
3	Cell Cycle, Mitotic ⁶⁵ Show member pathways Cell Cycle ⁶⁵ M Phase ⁶⁵	13.34	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
4	DNA Double-Strand Break Repair ⁶⁵ Show member pathways Chk1/Chk2(Cds1) mediated inactivation of Cyclin B-Cdk1 complex ⁶⁵ DNA damage_DNA-damage-induced responses ²² DNA Repair ⁶⁵ G2/M DNA damage checkpoint ⁶⁵ HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) ⁶⁵ HDR through MMEJ (alt-NHEJ) ⁶⁵ Homology Directed Repair ⁶⁵ Non-homologous end joining ¹ Non-homologous end-joining ³⁶ Processing of DNA double-strand break ends ⁶⁵	13.18	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
5	Chromatin organization ⁶⁵ Show member pathways Chromatin modifying enzymes ⁶⁵ HATs acetylate histones ⁶⁵	12.99	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
6	Deubiquitination ⁶⁵ Show member pathways Ub-specific processing proteases ⁶⁵	12.62	UIMC1 H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
7	Cell Cycle Checkpoints ⁶⁵ Show member pathways G2/M Checkpoints ⁶⁵	12.59	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
8	DNA Damage ⁴	12.46	UIMC1 UBE2N TP53BP1 H2AX BRCC3 BRCA1
9	SUMOylation ⁶⁵ Show member pathways Processing and activation of SUMO ⁶⁵ SUMO E3 ligases SUMOylate target proteins ⁶⁵ SUMO is conjugated to E1 (UBA2-SAE1) ⁶⁵ SUMO is proteolytically processed ⁶⁵ SUMO is transferred from E1 to E2 (UBE2I, UBC9) ⁶⁵ SUMOylation of chromatin organization proteins ⁶⁵ SUMOylation of DNA damage response and repair proteins ⁶⁵ SUMOylation of transcription factors ⁶⁵	12.4	TP53BP1 RNF168 MDC1 BRCA1
10	Meiosis ⁶⁵ Show member pathways Meiotic recombination ⁶⁵ Meiotic synapsis ⁶⁵	12.4	H2AX H2AC20 H2AC18 H2AC14 BRCA1
11	Chromosome Maintenance ⁶⁵ Show member pathways Deposition of new CENPA-containing nucleosomes at the centromere ⁶⁵ Nucleosome assembly ⁶⁵ Telomere Maintenance ⁶⁵	12.39	H2AX H2AC20 H2AC18 H2AC14
12	DNA Damage/Telomere Stress Induced Senescence ⁶⁵ Show member pathways Formation of Senescence-Associated Heterochromatin Foci (SAHF) ⁶⁵ Packaging Of Telomere Ends ⁶⁵ Signal transduction Activin A signaling regulation ²²	12.33	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
13	DNA Double Strand Break Response ⁶⁵ Show member pathways Nonhomologous End-Joining (NHEJ) ⁶⁵ Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks ⁶⁵ Sensing of DNA Double Strand Breaks ⁶⁵	12.27	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
14	Resolution of D-loop Structures through Holliday Junction Intermediates ⁶⁵ Show member pathways Homologous recombination ³⁶ Homologous recombination ¹ Resolution of D-Loop Structures ⁶⁵ Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) ⁶⁵	11.93	UIMC1 BRCC3 BRCA1
15	Necroptosis ³⁶ Show member pathways Nanoparticle triggered regulated necrosis ¹	11.84	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
16	ATM Pathway ⁶³ Show member pathways ATM Signaling Pathway ¹	11.76	TP53BP1 MDC1 H2AX BRCA1
17	ATM Signaling Network in Development and Disease ¹	11.52	TP53BP1 RNF8 RNF168 MDC1 H2AX
18	Metalloprotease DUBs ⁶⁵	10.94	UIMC1 H2AC20 H2AC18 H2AC15 H2AC14 H2AC13

Sources

GO Terms for Riddle Syndrome

Cellular components related to Riddle Syndrome according to GeneCards Suite gene sharing:

(show all 12)

#	Name	GO ID	Score	Top Affiliating Genes
1	nucleoplasm	GO:0005654	10.19	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
2	extracellular exosome	GO:0070062	10.13	UBE2N H2AX H2AC20 H2AC18 H2AC15 H2AC14
3	nucleus	GO:0005634	10.11	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
4	nuclear chromatin	GO:0000790	9.91	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
5	nuclear body	GO:0016604	9.85	UIMC1 TP53BP1 MDC1 ERCC6 BRCA1
6	ubiquitin ligase complex	GO:0000151	9.72	UBE2N RNF8 RNF168 BRCC3 BRCA1
7	site of double-strand break	GO:0035861	9.71	TP53BP1 RNF8 RNF168 H2AX
8	chromosome, telomeric region	GO:0000781	9.65	TP53BP1 RNF8 H2AX
9	nucleosome	GO:0000786	9.61	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
10	BRCA1-A complex	GO:0070531	9.54	UIMC1 BRCC3 BRCA1
11	site of DNA damage	GO:0090734	9.51	H2AX ERCC6
12	chromosome	GO:0005694	9.44	TP53BP1 RNF8 MDC1 H2AX H2AC20 H2AC18

Biological processes related to Riddle Syndrome according to GeneCards Suite gene sharing:

(show all 22)

#	Name	GO ID	Score	Top Affiliating Genes
1	cellular response to DNA damage stimulus	GO:0006974	10.07	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
2	biological_process	GO:0008150	10.02	H2AC20 H2AC18 H2AC15 H2AC14 H2AC13 H2AC12
3	DNA repair	GO:0006281	10.02	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
4	cell cycle	GO:0007049	9.99	RNF8 MDC1 H2AX BRCC3 BRCA1
5	double-strand break repair	GO:0006302	9.91	UIMC1 RNF8 RNF168 H2AX BRCC3 BRCA1
6	response to ionizing radiation	GO:0010212	9.88	UIMC1 RNF8 RNF168 H2AX BRCC3 BRCA1
7	positive regulation of DNA repair	GO:0045739	9.86	UIMC1 UBE2N RNF8 RNF168 H2AX ERCC6
8	chromatin silencing	GO:0006342	9.81	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13
9	double-strand break repair via homologous recombination	GO:0000724	9.73	UBE2N H2AX BRCA1
10	protein K63-linked ubiquitination	GO:0070534	9.71	UBE2N RNF8 RNF168
11	DNA damage checkpoint	GO:0000077	9.69	TP53BP1 H2AX ERCC6
12	signal transduction involved in G2 DNA damage checkpoint	GO:0072425	9.63	UIMC1 BRCC3 BRCA1
13	response to X-ray	GO:0010165	9.61	ERCC6 BRCC3
14	double-strand break repair via nonhomologous end joining	GO:0006303	9.61	UIMC1 UBE2N TP53BP1 RNF8 RNF168 MDC1
15	isotype switching	GO:0045190	9.6	RNF8 RNF168
16	DNA double-strand break processing	GO:0000729	9.58	UBE2N BRCA1
17	postreplication repair	GO:0006301	9.58	UBE2N BRCA1
18	negative regulation of transcription elongation from RNA polymerase II promoter	GO:0034244	9.57	RNF8 RNF168
19	histone H2A ubiquitination	GO:0033522	9.55	RNF8 RNF168
20	histone H2A K63-linked deubiquitination	GO:0070537	9.52	UIMC1 BRCC3
21	histone H2A K63-linked ubiquitination	GO:0070535	9.49	RNF8 RNF168
22	chromatin organization	GO:0006325	9.44	UIMC1 RNF8 RNF168 H2AX H2AC20 H2AC18

Molecular functions related to Riddle Syndrome according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	molecular_function	GO:0003674	9.85	H2AC20 H2AC18 H2AC15 H2AC14 H2AC12
2	DNA binding	GO:0003677	9.73	TP53BP1 H2AX H2AC20 H2AC18 H2AC15 H2AC14
3	ubiquitin-protein transferase activity	GO:0004842	9.71	UBE2N RNF8 RNF168 BRCA1
4	enzyme binding	GO:0019899	9.65	H2AX H2AC15 H2AC13 H2AC11 BRCA1
5	histone binding	GO:0042393	9.55	UIMC1 TP53BP1 RNF8 RNF168 H2AX
6	ubiquitin binding	GO:0043130	9.54	UBE2N RNF8 RNF168
7	damaged DNA binding	GO:0003684	9.5	TP53BP1 H2AX BRCA1
8	K63-linked polyubiquitin modification-dependent protein binding	GO:0070530	9.43	UIMC1 RNF168
9	protein heterodimerization activity	GO:0046982	9.28	H2AX H2AC20 H2AC18 H2AC15 H2AC14 H2AC13

Sources

Sources for Riddle Syndrome

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

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⁹ Cosmic

¹⁰ dbSNP

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¹⁶ DrugBank

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¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

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³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

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⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

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⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NIH Rare Diseases

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Riddle Syndrome (RIDL)

Aliases & Classifications for Riddle Syndrome

MalaCards integrated aliases for Riddle Syndrome:

Characteristics:

Orphanet epidemiological data:

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Classifications:

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Summaries for Riddle Syndrome

Related Diseases for Riddle Syndrome

Diseases related to Riddle Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

Graphical network of the top 20 diseases related to Riddle Syndrome:

Symptoms & Phenotypes for Riddle Syndrome

Human phenotypes related to Riddle Syndrome:

Symptoms via clinical synopsis from OMIM:

Clinical features from OMIM:

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Cochrane evidence based reviews: riddle syndrome

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Genes for Riddle Syndrome

Genes related to Riddle Syndrome (1 elite genes):

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Expression for Riddle Syndrome

Pathways for Riddle Syndrome

Pathways related to Riddle Syndrome according to GeneCards Suite gene sharing:

GO Terms for Riddle Syndrome

Cellular components related to Riddle Syndrome according to GeneCards Suite gene sharing:

Biological processes related to Riddle Syndrome according to GeneCards Suite gene sharing:

Molecular functions related to Riddle Syndrome according to GeneCards Suite gene sharing:

Sources for Riddle Syndrome