RSPH3

radial spoke head 3, the group of Axonemal radial spoke subunits

Basic information

Region (hg38): 6:158970084-159000202

Previous symbols: [ "RSHL2" ]

Links

ENSG00000130363 ∙ NCBI:83861 ∙ OMIM:615876 ∙ HGNC:21054 ∙ Uniprot:Q86UC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 32 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 32 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 32 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 32 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 32	AR	Allergy/Immunology/Infectious	Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial	Allergy/Immunology/Infectious	26073779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPH3 gene.

• Primary_ciliary_dyskinesia_32 (175 variants)
• Inborn_genetic_diseases (62 variants)
• not_provided (25 variants)
• RSPH3-related_disorder (6 variants)
• Primary_ciliary_dyskinesia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPH3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000031924.8. 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				43	2	45
missense			90	14	4	108
nonsense	5	1				6
start loss						0
frameshift	4	1	3			8
splice donor/acceptor (+/-2bp)	2	2				4
Total	11	4	93	57	6

Highest pathogenic variant AF is 0.000014897616

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPH3	protein_coding	protein_coding	ENST00000252655	8	27317

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.87e-8	0.929	125712	0	35	125747	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0674	316	319	0.989	0.0000164	3597
Missense in Polyphen		73	94.228	0.77471		1121
Synonymous	-0.721	130	120	1.08	0.00000569	1131
Loss of Function	1.82	15	24.8	0.606	0.00000149	247

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000374	0.000373
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.000163	0.000163
South Asian	0.000168	0.0000980
Other	0.00104	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a protein kinase A-anchoring protein that scaffolds the cAMP-dependent protein kinase holoenzyme. May serve as a point of convergence for MAPK and PKA signaling in cilia. {ECO:0000269|PubMed:19684019}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 32 (CILD32) [MIM:616481]: A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. {ECO:0000269|PubMed:26073779}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0724

Intolerance Scores

• loftool: 0.808
• rvis_EVS: 1.16
• rvis_percentile_EVS: 92.63

Haploinsufficiency Scores

• pHI: 0.0665
• hipred: N
• hipred_score: 0.281
• ghis: 0.450

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0510

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Rsph3a

Gene ontology

• Cellular component: cytoplasm;cytoskeleton;cilium
• Molecular function: protein binding