CFAP53

protein-coding

cilia and flagella associated protein 53, the group of Cilia and flagella associated

Gene summary

This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

Previous symbols:

CCDC11

MANE transcript

NM_145020.5

Inheritance

AD, AR

ClinVar variants

P:17U:101B:39

Top phenotype

Heterotaxy, visceral, 6, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr18:50,227,193-50,266,495

External References & Databases

Ensembl (ENSG00000172361)

Transcript & Mutation Effects

hg38 • Region Span ~39.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

situs inversusSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010029

Submitter: Orphanet

heterotaxy, visceral, 6, autosomalSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013887

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Heterotaxy, visceral, 6, autosomal recessiveAR

Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Pulmonary

Intervention: Allergy/Immunology/Infectious; Cardiovascular; Pulmonary

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management; Pulmonary surveillance may be beneficial to assess respiratory function and institute early management; 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

Refs: 22577226; 25504577

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFAP53 variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 84

Heterotaxy, visceral, 6, autosomalTotal: 77

not providedTotal: 27

not specifiedTotal: 14

CFAP53-related disorderTotal: 4

HeterotaxyTotal: 2

DextrocardiaTotal: 2

Hypoplastic left heart syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145020.5. 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		1 clinvar	1 clinvar	25 clinvar	2 clinvar	29
missense			97 clinvar	10 clinvar	2 clinvar	109
nonsense	1 clinvar	6 clinvar	1 clinvar			8
start loss			1 clinvar			1
frameshift	1 clinvar	2 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	5 clinvar	1 clinvar			7
Total	3	14	101	35	4	157

Highest pathogenic variant AF is 0.00012415327

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145020.5	RefSeq	NP_659457.2	8	MANE Select
ENST00000398545.5	Ensembl	ENSP00000381553.3	8	MANE Select
ENST00000880606.1	Ensembl	ENSP00000550665.1	8	Standard
ENST00000880606.2	Ensembl	ENSP00000550665.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cfap53	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cfap53

Danio rerio

Structure: otolith

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cilium movement
determination of left/right symmetry
cilium assembly
epithelial cilium movement involved in determination of left/right asymmetry

Molecular Function

protein binding

Cellular Component

cellular_component
cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398545
Coding exons: 8
Length: 39330
Individuals with no LoFs: 124634
Homozygous LoFs: 1
Heterozygous LoFs: 166
Defined: 124801
p: 0.000669

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.577	300	273	1.10	0.0000154	3435
Missense (PolyPhen)		95	74.709	1.2716		950
Synonymous	-0.749	102	92.8	1.10	0.00000461	852
Loss of Function	0.0973	28	28.6	0.980	0.00000177	327

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00045	rare
Latino/Admixed American	0.00090	0.00087	rare
Ashkenazi Jewish	0.0020	0.0020	notable
East Asian	0.00045	0.00045	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00061	0.00060	rare
South Asian	0.00086	0.00085	rare
Other	0.00085	0.00082	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the beating of primary cilia and thereby be involved in the establishment of organ laterality during embryogenesis. {ECO:0000269|PubMed:26531781}.;

Recessive Scores

pRec: 0.0718

Intolerance Scores

RVIS EVS: 0.38
RVIS percentile EVS: 75.58

Essentials

Essential (gene trap): N