RSPH9

radial spoke head component 9, the group of Axonemal radial spoke subunits

Basic information

Region (hg38): 6:43645035-43672600

Previous symbols: [ "MRPS18AL1", "C6orf206" ]

Links

ENSG00000172426 ∙ NCBI:221421 ∙ OMIM:612648 ∙ HGNC:21057 ∙ Uniprot:Q9H1X1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 12 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 12 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 12 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 12 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 12	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	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, though measures including lobectomy or lung transplantation may be necessary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary	19200523; 20301301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPH9 gene.

• Primary ciliary dyskinesia (102 variants)
• not provided (36 variants)
• Primary ciliary dyskinesia 12 (24 variants)
• Inborn genetic diseases (17 variants)
• not specified (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPH9 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			2	25	1	28
missense			62	5	1	68
nonsense	5					5
start loss	2					2
frameshift	3					3
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)		3				3
splice region		1		3		4
non coding			8	9	21	38
Total	11	3	73	39	23

Highest pathogenic variant AF is 0.0000591

Variants in RSPH9

This is a list of pathogenic ClinVar variants found in the RSPH9 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-43645081-A-G		not specified • Primary ciliary dyskinesia 12	Benign (Dec 31, 2018)
6-43645099-A-G		Primary ciliary dyskinesia	Pathogenic (Feb 04, 2022)
6-43645099-A-T		Primary ciliary dyskinesia	Pathogenic (Dec 09, 2023)
6-43645100-T-C		Primary ciliary dyskinesia	Pathogenic (Oct 03, 2023)
6-43645107-C-G		Primary ciliary dyskinesia	Likely benign (Feb 09, 2023)
6-43645109-A-G		Primary ciliary dyskinesia	Uncertain significance (Mar 11, 2022)
6-43645116-C-G		Primary ciliary dyskinesia	Likely benign (Jul 18, 2022)
6-43645122-GT-TG		Primary ciliary dyskinesia	Uncertain significance (Jan 09, 2024)
6-43645123-T-C		Primary ciliary dyskinesia	Uncertain significance (Mar 14, 2020)
6-43645125-T-C		Primary ciliary dyskinesia	Likely benign (Jan 25, 2024)
6-43645129-G-A		Primary ciliary dyskinesia	Uncertain significance (May 02, 2022)
6-43645150-C-T		Primary ciliary dyskinesia 12	Pathogenic (Sep 05, 2013)
6-43645164-G-A		Primary ciliary dyskinesia	Likely benign (Mar 18, 2023)
6-43645170-T-G		Primary ciliary dyskinesia	Likely benign (May 16, 2023)
6-43645171-C-T		Primary ciliary dyskinesia	Uncertain significance (Jan 23, 2024)
6-43645193-T-C		Primary ciliary dyskinesia	Uncertain significance (Sep 23, 2014)
6-43645196-T-C		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Mar 05, 2024)
6-43645206-G-A			Likely benign (Feb 15, 2018)
6-43645210-G-T		Primary ciliary dyskinesia 12	Uncertain significance (Jan 13, 2018)
6-43645215-C-A		Primary ciliary dyskinesia	Pathogenic (May 16, 2023)
6-43645216-C-G		Primary ciliary dyskinesia	Uncertain significance (May 27, 2022)
6-43645216-C-T		Primary ciliary dyskinesia	Uncertain significance (Nov 09, 2023)
6-43645220-A-G		Primary ciliary dyskinesia	Uncertain significance (Sep 06, 2023)
6-43645222-G-C		Primary ciliary dyskinesia	Uncertain significance (Jun 22, 2022)
6-43645224-T-G		Primary ciliary dyskinesia	Uncertain significance (Dec 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPH9	protein_coding	protein_coding	ENST00000372165	6	27554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.39e-9	0.0797	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.237	164	173	0.949	0.00000917	1983
Missense in Polyphen		37	42.588	0.86878		460
Synonymous	0.180	71	73.0	0.973	0.00000403	625
Loss of Function	-0.117	13	12.6	1.04	6.26e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000671	0.000666
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.000490	0.000490
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable component of the axonemal radial spoke head. Radial spokes are regularly spaced along cilia, sperm and flagella axonemes. They consist of a thin stalk, which is attached to a subfiber of the outer doublet microtubule, and a bulbous head, which is attached to the stalk and appears to interact with the projections from the central pair of microtubules. {ECO:0000269|PubMed:19200523}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 12 (CILD12) [MIM:612650]: 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; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. {ECO:0000269|PubMed:19200523}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.239
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.193
• hipred: N
• hipred_score: 0.123
• ghis: 0.448

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.115

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rsph9
• 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); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: rsph9
• Affected structure: spinal cord neural tube
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: cilium movement;axoneme assembly;motile cilium assembly;cilium movement involved in cell motility
• Cellular component: axoneme;motile cilium;9+2 motile cilium
• Molecular function: protein binding