CFAP251

protein-coding

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

Gene summary

This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

Previous symbols:

WDR66

MANE transcript

NM_144668.6

Inheritance

ClinVar variants

P:15U:163B:31

Top phenotype

Spermatogenic failure 33

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr12:121,918,592-122,003,927

External References & Databases

Ensembl (ENSG00000158023)

Transcript & Mutation Effects

hg38 • Region Span ~85.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 33STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0029147

Submitter: Labcorp Genetics (formerly Invitae)

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 33AR

Manifestation: Genitourinary

Intervention: General

Rationale: 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

Refs: 30122540; 30122541

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFAP251 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 159

CFAP251-related disorderTotal: 20

not providedTotal: 16

Spermatogenic failure 33Total: 16

Non-syndromic male infertility due to sperm motility disorderTotal: 2

Male infertility with teratozoospermia due to single gene mutationTotal: 2

dysplasia of the mitochondrial sheathTotal: 1

multiple morphologic abnormalities of the sperm flagellumTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144668.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	14 clinvar	2 clinvar	18
missense			152 clinvar	14 clinvar	1 clinvar	167
nonsense	1 clinvar	4 clinvar	3 clinvar			8
start loss						0
frameshift	4 clinvar	4 clinvar				8
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	6 clinvar			8
Total	6	9	163	28	3	209

Highest pathogenic variant AF is 0.002048672

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144668.6	RefSeq	NP_653269.3	21	MANE Select
ENST00000288912.9	Ensembl	ENSP00000288912.4	21	MANE Select
NM_001178003.2	RefSeq	NP_001171474.1	17	Standard
ENST00000397454.2	Ensembl	ENSP00000380595.2	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wdr66	Danio rerio	Structure: thrombocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

wdr66

Danio rerio

Structure: thrombocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cilium movement

Cellular Component

radial spoke stalk
axoneme
motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288912
Coding exons: 21
Length: 86066
Individuals with no LoFs: 124884
Homozygous LoFs: 0
Heterozygous LoFs: 132
Defined: 125016
p: 0.000528

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.584	579	620	0.934	0.0000324	7540
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0011	notable
Latino/Admixed American	0.00083	0.00075	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00034	0.00033	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00063	0.00063	rare
South Asian	0.00018	0.00016	rare
Other	0.00070	0.00066	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.545

Gene Damage Prediction

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