RSPH4A

radial spoke head component 4A, the group of Axonemal radial spoke subunits

Basic information

Region (hg38): 6:116616478-116632985

Previous symbols: [ "RSHL3" ]

Links

ENSG00000111834 ∙ NCBI:345895 ∙ OMIM:612647 ∙ HGNC:21558 ∙ Uniprot:Q5TD94 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 11 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 11 (Definitive), mode of inheritance: AR
• primary ciliary dyskinesia 11 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 11 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 11	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; Pulmonary	19200523; 20301301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPH4A gene.

• Primary ciliary dyskinesia (246 variants)
• Primary ciliary dyskinesia 11 (74 variants)
• not provided (50 variants)
• not specified (26 variants)
• Inborn genetic diseases (18 variants)
• RSPH4A-related condition (4 variants)
• Kartagener syndrome (2 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPH4A 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	48		50
missense	2		145	8	5	160
nonsense	15	2				17
start loss						0
frameshift	9	6				15
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1		1			2
splice region	1		1			2
non coding			10	20	17	47
Total	27	8	161	76	22

Highest pathogenic variant AF is 0.000276

Variants in RSPH4A

This is a list of pathogenic ClinVar variants found in the RSPH4A region.

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

Position	Type	Phenotype	Significance	ClinVar
6-116616536-A-G		Primary ciliary dyskinesia 11	Uncertain significance (Jan 13, 2018)
6-116616574-T-C		Primary ciliary dyskinesia 11	Uncertain significance (Jan 12, 2018)
6-116616606-T-TTCACGCCCC		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Jul 11, 2020)
6-116616608-TTCTT-CACGCCCCTTTCATCCA		not specified • Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Jun 14, 2016)
6-116616611-T-A		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Jul 11, 2020)
6-116616612-T-TCCA		Primary ciliary dyskinesia	Conflicting classifications of pathogenicity (Jul 11, 2020)
6-116616634-C-G		Primary ciliary dyskinesia	Pathogenic (Sep 27, 2017)
6-116616638-C-A		Primary ciliary dyskinesia	Likely benign (Mar 26, 2021)
6-116616638-C-T		Primary ciliary dyskinesia	Likely benign (May 21, 2022)
6-116616641-C-T		Primary ciliary dyskinesia	Likely benign (Aug 09, 2022)
6-116616648-C-A		Primary ciliary dyskinesia	Uncertain significance (Dec 25, 2021)
6-116616658-A-T		Primary ciliary dyskinesia	Uncertain significance (Jun 28, 2022)
6-116616662-C-T			Likely benign (Feb 01, 2023)
6-116616669-G-C		Primary ciliary dyskinesia	Uncertain significance (Aug 05, 2022)
6-116616688-G-A		not specified	Uncertain significance (Jun 04, 2019)
6-116616695-G-A		Primary ciliary dyskinesia	Pathogenic (Feb 11, 2023)
6-116616707-A-G		Primary ciliary dyskinesia	Uncertain significance (Apr 11, 2014)
6-116616714-T-C		Primary ciliary dyskinesia	Uncertain significance (Dec 25, 2022)
6-116616714-TC-CT		Primary ciliary dyskinesia	Uncertain significance (Oct 05, 2022)
6-116616715-C-T		Primary ciliary dyskinesia	Uncertain significance (Dec 25, 2022)
6-116616722-A-G		Primary ciliary dyskinesia	Likely benign (Jan 08, 2024)
6-116616725-TTCTGAGCCTGAGTCG-T		Primary ciliary dyskinesia	Uncertain significance (Aug 30, 2021)
6-116616726-T-C		Primary ciliary dyskinesia 11	Uncertain significance (-)
6-116616727-C-A		Primary ciliary dyskinesia	Uncertain significance (Jun 27, 2022)
6-116616733-C-G		Primary ciliary dyskinesia	Uncertain significance (Sep 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPH4A	protein_coding	protein_coding	ENST00000229554	6	16507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.57e-11	0.875	125651	0	96	125747	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.319	354	371	0.953	0.0000179	4717
Missense in Polyphen		138	138.34	0.99754		1843
Synonymous	0.320	130	135	0.965	0.00000652	1355
Loss of Function	1.83	21	32.2	0.652	0.00000181	373

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000727	0.000727
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000925	0.000925
Finnish	0.00	0.00
European (Non-Finnish)	0.000337	0.000334
Middle Eastern	0.000925	0.000925
South Asian	0.000297	0.000294
Other	0.00115	0.00114

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}.

Intolerance Scores

• loftool: 0.990
• rvis_EVS: 0.82
• rvis_percentile_EVS: 88.07

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.200
• ghis: 0.429

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rsph4a

Gene ontology

• Biological process: cilium movement;axoneme assembly
• Cellular component: radial spoke;nucleus;nucleoplasm;nucleolus;axoneme;motile cilium
• Molecular function: molecular_function