RIPPLY2

ripply transcriptional repressor 2

Basic information

Region (hg38): 6:83853360-83857515

Previous symbols: [ "C6orf159" ]

Links

ENSG00000203877 ∙ NCBI:134701 ∙ OMIM:609891 ∙ HGNC:21390 ∙ Uniprot:Q5TAB7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylocostal dysostosis 6, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive spondylocostal dysostosis (Supportive), mode of inheritance: AR
• spondylocostal dysostosis 6, autosomal recessive (Limited), mode of inheritance: AR
• spondylocostal dysostosis 6, autosomal recessive (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylocostal dysostosis 6, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	25343988

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIPPLY2 gene.

• not_provided (66 variants)
• not_specified (23 variants)
• RIPPLY2-related_disorder (2 variants)
• Spondylocostal_dysostosis_6,_autosomal_recessive (2 variants)
• Spondylocostal_dysostosis_2,_autosomal_recessive (2 variants)
• Klippel-Feil_syndrome_2,_autosomal_recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIPPLY2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001009994.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	13	2	16
missense			38	2		40
nonsense		1				1
start loss						0
frameshift		1	2			3
splice donor/acceptor (+/-2bp)			2			2
Total	0	2	43	15	2

Highest pathogenic variant AF is 0.000172275

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIPPLY2	protein_coding	protein_coding	ENST00000369689	4	4250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00939	0.827	125687	0	32	125719	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.555	82	69.0	1.19	0.00000314	817
Missense in Polyphen		25	20.427	1.2239		286
Synonymous	0.941	21	27.2	0.771	0.00000137	230
Loss of Function	1.11	4	7.22	0.554	3.05e-7	91

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites (By similarity). {ECO:0000250|UniProtKB:Q2WG76}.
• Disease: DISEASE: Spondylocostal dysostosis 6, autosomal recessive (SCDO6) [MIM:616566]: A form of spondylocostal dysostosis, a condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life. {ECO:0000269|PubMed:25343988}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gene regulatory network modelling somitogenesis (Consensus)

Intolerance Scores

• loftool: 0.419
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.123
• ghis: 0.622

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ripply2
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; respiratory system phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;ossification;somitogenesis;Notch signaling pathway;determination of left/right symmetry;embryonic pattern specification;somite rostral/caudal axis specification;post-anal tail morphogenesis;bone morphogenesis
• Cellular component: nucleus
• Molecular function: protein binding