CFAP251

cilia and flagella associated protein 251, the group of WD repeat domain containing

Basic information

Region (hg38): 12:121918592-122003927

Previous symbols: [ "WDR66" ]

Links

ENSG00000158023 ∙ NCBI:144406 ∙ OMIM:618146 ∙ HGNC:28506 ∙ Uniprot:Q8TBY9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic male infertility due to sperm motility disorder (Supportive), mode of inheritance: AR
• spermatogenic failure 33 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 33	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	Genitourinary	30122540; 30122541

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFAP251 gene.

• not_specified (132 variants)
• CFAP251-related_disorder (19 variants)
• not_provided (14 variants)
• Spermatogenic_failure_33 (11 variants)
• Non-syndromic_male_infertility_due_to_sperm_motility_disorder (2 variants)
• Spermatogenic_failure_18 (2 variants)
• Male_infertility_with_teratozoospermia_due_to_single_gene_mutation (2 variants)
• dysplasia_of_the_mitochondrial_sheath (1 variants)
• multiple_morphologic_abnormalities_of_the_sperm_flagellum (1 variants)
• Reduced_sperm_motility (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFAP251 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000144668.6. 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				13	2	15
missense			128	11	1	140
nonsense	1	2				3
start loss						0
frameshift	4	2				6
splice donor/acceptor (+/-2bp)						0
Total	5	4	128	24	3

Highest pathogenic variant AF is 0.00204867

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFAP251	protein_coding	protein_coding	ENST00000288912	21	86066

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.94e-13	1.00	124884	0	132	125016	0.000528

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.584	579	620	0.934	0.0000324	7540
Missense in Polyphen		97	126.84	0.76474		1570
Synonymous	0.501	232	242	0.959	0.0000145	2174
Loss of Function	3.28	30	56.7	0.529	0.00000268	716

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00194	0.00193
Ashkenazi Jewish	0.00	0.00
East Asian	0.000341	0.000330
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000630	0.000626
Middle Eastern	0.000341	0.000330
South Asian	0.000178	0.000163
Other	0.000701	0.000658

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate cilium motility through its role in the assembly of the axonemal radial spokes. {ECO:0000250|UniProtKB:A8IRK7, ECO:0000250|UniProtKB:Q24DE2}.

Intolerance Scores

• loftool: 0.966
• rvis_EVS: 1.41
• rvis_percentile_EVS: 94.8

Haploinsufficiency Scores

• pHI: 0.163
• hipred: N
• hipred_score: 0.233
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.545

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr66

Zebrafish Information Network

• Gene name: wdr66
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cilium movement
• Cellular component: radial spoke stalk;axoneme;motile cilium