RSPH1

radial spoke head component 1, the group of Axonemal radial spoke subunits

Basic information

Region (hg38): 21:42472486-42496246

Previous symbols: [ "TSGA2" ]

Links

ENSG00000160188 ∙ NCBI:89765 ∙ OMIM:609314 ∙ HGNC:12371 ∙ Uniprot:Q8WYR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 24 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 24 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 24 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 24 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 24	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	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary	20301301; 23993197; 24518672

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPH1 gene.

• Primary ciliary dyskinesia (14 variants)
• Primary ciliary dyskinesia 24 (4 variants)
• Kartagener syndrome (2 variants)
• RSPH1-related disorder (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPH1 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			4	46	6	56
missense	1	1	71	8	2	83
nonsense	4	4				8
start loss	1					1
frameshift	5	1				6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	1				4
splice region	1	1	4	9		15
non coding				44	27	71
Total	14	7	76	98	35

Highest pathogenic variant AF is 0.000441

Variants in RSPH1

This is a list of pathogenic ClinVar variants found in the RSPH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-42472531-T-C			Benign (Nov 27, 2018)
21-42472589-C-T			Likely benign (May 28, 2019)
21-42472629-G-A			Likely benign (Jun 09, 2019)
21-42472636-C-T			Benign (May 15, 2019)
21-42472665-G-A			Benign (Nov 12, 2018)
21-42472765-G-A			Benign (Feb 05, 2019)
21-42472829-G-A		Primary ciliary dyskinesia	Uncertain significance (Sep 07, 2022)
21-42472832-C-G		Primary ciliary dyskinesia 24 • Primary ciliary dyskinesia	Uncertain significance (Apr 28, 2022)
21-42472836-C-T		Primary ciliary dyskinesia	Likely benign (Feb 06, 2022)
21-42472841-T-C		Primary ciliary dyskinesia • Primary ciliary dyskinesia 24 • Inborn genetic diseases • RSPH1-related disorder	Conflicting classifications of pathogenicity (Jan 21, 2024)
21-42472846-T-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
21-42472874-A-C		Primary ciliary dyskinesia	Likely benign (Nov 12, 2023)
21-42473074-G-A			Benign (Nov 12, 2018)
21-42475587-T-C			Benign (Dec 17, 2018)
21-42475588-G-A			Benign (Dec 17, 2018)
21-42475614-T-G			Benign (Jan 16, 2019)
21-42475749-C-T			Likely benign (Aug 13, 2019)
21-42475786-C-T			Benign (May 28, 2019)
21-42475884-C-T		Primary ciliary dyskinesia	Likely benign (Jul 29, 2023)
21-42475885-G-A		Primary ciliary dyskinesia	Likely benign (Jun 13, 2022)
21-42475891-A-T		Primary ciliary dyskinesia • Primary ciliary dyskinesia 24	Benign/Likely benign (Jan 08, 2024)
21-42475905-C-T		Primary ciliary dyskinesia • RSPH1-related disorder	Likely benign (Jan 29, 2024)
21-42475911-A-C			Uncertain significance (Apr 28, 2023)
21-42475915-C-T		Primary ciliary dyskinesia	Uncertain significance (Aug 05, 2021)
21-42475916-G-A		Primary ciliary dyskinesia • Inborn genetic diseases	Uncertain significance (Sep 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPH1	protein_coding	protein_coding	ENST00000291536	9	23869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000205	0.898	125641	0	107	125748	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.138	186	191	0.972	0.0000114	2022
Missense in Polyphen		60	70.466	0.85148		759
Synonymous	-0.247	77	74.3	1.04	0.00000492	552
Loss of Function	1.61	12	19.7	0.608	9.03e-7	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00106	0.00106
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000536	0.000519
Middle Eastern	0.0000544	0.0000544
South Asian	0.000261	0.000261
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play an important role in male meiosis (By similarity). It is necessary for proper building of the axonemal central pair and radial spokes. {ECO:0000250, ECO:0000269|PubMed:23993197}.

Recessive Scores

• pRec: 0.0951

Intolerance Scores

• loftool: 0.788
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.52

Haploinsufficiency Scores

• pHI: 0.0512
• hipred: N
• hipred_score: 0.205
• ghis: 0.426

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.112

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rsph1
• Phenotype: reproductive system phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: spermatid development;axoneme assembly;meiotic cell cycle
• Cellular component: condensed nuclear chromosome;outer dense fiber;nucleus;cytosol;motile cilium;meiotic spindle
• Molecular function: protein binding