RIPK4

receptor interacting serine/threonine kinase 4, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 21:41739368-41767089

Previous symbols: [ "ANKRD3" ]

Links

ENSG00000183421 ∙ NCBI:54101 ∙ OMIM:605706 ∙ HGNC:496 ∙ Uniprot:P57078 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bartsocas-Papas syndrome 1 (Supportive), mode of inheritance: AR
• Bartsocas-Papas syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bartsocas-Papas syndrome 1; CHAND syndrome	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	Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Ophthalmologic	4339984; 10925380; 15264293; 23074676; 22197489; 22197488; 26129644; 28940926

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIPK4 gene.

• Bartsocas-Papas syndrome 1 (123 variants)
• not provided (101 variants)
• Inborn genetic diseases (36 variants)
• not specified (13 variants)
• Popliteal pterygium syndrome (2 variants)
• Curly hair, ankyloblepharon, nail dysplasia syndrome;Bartsocas-Papas syndrome 1 (1 variants)
• RIPK4-related condition (1 variants)
• Curly hair, ankyloblepharon, nail dysplasia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIPK4 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	29	12	49
missense		1	62	9	2	74
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding			36	21	26	83
Total	0	2	106	59	40

Variants in RIPK4

This is a list of pathogenic ClinVar variants found in the RIPK4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-41739391-T-G		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739418-A-C		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739462-G-A		Bartsocas-Papas syndrome 1	Uncertain significance (Apr 27, 2017)
21-41739477-A-T		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)
21-41739590-G-A		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)
21-41739604-C-T		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)
21-41739632-T-C		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739635-T-A		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739646-T-C		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739666-A-G		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)
21-41739687-C-T		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739721-A-G		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739757-G-A		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41739798-A-AC		Popliteal pterygium syndrome	Uncertain significance (Jun 14, 2016)
21-41739813-C-A		Bartsocas-Papas syndrome 1	Benign (Apr 27, 2017)
21-41739855-C-T		Bartsocas-Papas syndrome 1	Benign (Apr 27, 2017)
21-41739860-G-C		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)
21-41739877-C-T		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41740014-G-A		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)
21-41740015-T-C		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 13, 2018)
21-41740054-A-ACT		Popliteal pterygium syndrome	Benign (Jun 14, 2016)
21-41740090-T-C		Bartsocas-Papas syndrome 1	Likely benign (Apr 27, 2017)
21-41740091-A-T		Bartsocas-Papas syndrome 1	Benign (Apr 27, 2017)
21-41740097-C-T		Bartsocas-Papas syndrome 1	Likely benign (Apr 27, 2017)
21-41740109-G-A		Bartsocas-Papas syndrome 1	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIPK4	protein_coding	protein_coding	ENST00000332512	8	27738

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00396	0.996	125491	0	257	125748	0.00102

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.89	409	532	0.769	0.0000377	5032
Missense in Polyphen		134	207.51	0.64574		2011
Synonymous	-1.31	278	252	1.11	0.0000196	1659
Loss of Function	3.15	9	26.5	0.340	0.00000139	282

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000562	0.000558
Ashkenazi Jewish	0.00326	0.00318
East Asian	0.000438	0.000435
Finnish	0.00103	0.000878
European (Non-Finnish)	0.00157	0.00148
Middle Eastern	0.000438	0.000435
South Asian	0.000131	0.000131
Other	0.00135	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation. {ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:22197488}.
• Disease: DISEASE: Popliteal pterygium syndrome, lethal type (PPS-L) [MIM:263650]: An autosomal recessive disorder characterized by multiple popliteal pterygia leading to severe arthrogryposis, ankyloblepharon filiforme adnatum, filiform bands between the jaws, synostosis of the carpal/tarsal and phalangeal bones in the hands and feet, digital hypoplasia/aplasia, complete soft-tissue syndactyly, lack of nails, lack of scalp hair, eyebrows and eyelashes, blepharophimosis, cleft lip and/or palate, and hypoplastic external genitalia. Early lethality is common, although survival into childhood and beyond has been reported. {ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:22197489}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.172

Intolerance Scores

• loftool: 0.382
• rvis_EVS: -1.66
• rvis_percentile_EVS: 2.75

Haploinsufficiency Scores

• pHI: 0.217
• hipred: Y
• hipred_score: 0.682
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.684

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ripk4
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; limbs/digits/tail phenotype; digestive/alimentary 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); respiratory system phenotype

Gene ontology

• Biological process: morphogenesis of an epithelium;protein phosphorylation;positive regulation of NF-kappaB transcription factor activity
• Cellular component: cytoplasm;membrane
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding