CEP83

protein-coding

centrosomal protein 83

Gene summary

The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

Previous symbols:

CCDC41

MANE transcript

NM_016122.3

Inheritance

ClinVar variants

P:51U:224B:142

Top phenotype

Nephronophthisis 18

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr12:94,306,449-94,459,988

External References & Databases

Ensembl (ENSG00000173588)

Transcript & Mutation Effects

hg38 • Region Span ~153.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ciliopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: ClinGen

The *CEP83* gene is located on chromosome 12 at 12q22 and encodes centrosomal Protein 83, a critical protein found at the centriolar distal appendages that acts as a scaffold for primary cilium assembly. *CEP83* was first reported in connection with ciliopathy in 2014 (Failler et al., 2014, PMID: 24882706). Fourteen unique variants (six nonsense, four missense, three deletions, one frameshift) from ten probands across three publications have been identified (PMIDs: 24882706, 32173348, 33938610). The mechanism of pathogenicity is loss-of-function whereby its dysfunction leads to ciliopathies by impairing ciliary membrane docking and initial axoneme formation. This gene-disease relationship is also supported by protein interaction, expression, and functional alteration studies (PMIDs: 31455668, 32173348, 24882706). In summary, there is definitive evidence supporting the relationship between CEP83 and ciliopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on September 22nd, 2021 (SOP Version 8).

nephronophthisis 18STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014374

Submitter: Genomics England PanelApp

nephronophthisis 18STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014374

Submitter: Labcorp Genetics (formerly Invitae)

nephronophthisis 18DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014374

Submitter: G2P

nephronophthisis 18MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014374

Submitter: Ambry Genetics

nephronophthisis 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011190

Submitter: Orphanet

Clinical Genomic Database (CGD)

Nephronophthisis 18AR

Manifestation: Gastrointestinal; Neurologic; Ophthalmologic; Renal

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: 24882706

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEP83 variants in ClinVar

7 Conditions Cataloged

Nephronophthisis 18Total: 453

Inborn genetic diseasesTotal: 83

not providedTotal: 72

not specifiedTotal: 53

CEP83-related disorderTotal: 21

CiliopathyTotal: 2

NephronophthisisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016122.3. 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				126 clinvar		126
missense		5 clinvar	222 clinvar	15 clinvar	1 clinvar	243
nonsense	17 clinvar	11 clinvar	1 clinvar			29
start loss						0
frameshift	13 clinvar	2 clinvar	1 clinvar			16
splice donor/acceptor (+/-2bp)		3 clinvar				3
Total	30	21	224	141	1	417

Highest pathogenic variant AF is 0.00021637372

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016122.3	RefSeq	NP_057206.2	15	MANE Select
ENST00000397809.10	Ensembl	ENSP00000380911.4	15	MANE Select
NM_001042399.2	RefSeq	NP_001035858.1	15	Standard
NM_001346457.2	RefSeq	NP_001333386.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cep83	Danio rerio	Structure: olfactory pit Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

cep83

Danio rerio

Structure: olfactory pit

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Anchoring of the basal body to the plasma membrane
Cilium Assembly
Organelle biogenesis and maintenance

Biological Process

vesicle docking
cilium assembly
protein localization to centrosome
ciliary basal body-plasma membrane docking

Molecular Function

molecular_function
protein binding

Cellular Component

Golgi apparatus
centriole
cytosol
ciliary transition fiber

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397809
Coding exons: 15
Length: 153540
Individuals with no LoFs: 124706
Homozygous LoFs: 0
Heterozygous LoFs: 86
Defined: 124792
p: 0.000345

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.406	316	337	0.938	0.0000171	4612
Missense (PolyPhen)		87	100.71	0.86386		1510
Synonymous	-0.950	130	117	1.11	0.00000555	1197
Loss of Function	2.12	28	43.0	0.652	0.00000232	556

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00045	0.00045	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00049	0.00049	rare
South Asian	0.00020	0.00020	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the distal appendage region of the centriole involved in the initiation of primary cilium assembly. May collaborate with IFT20 in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium during the initiation of primary cilium assembly. {ECO:0000269|PubMed:23348840, ECO:0000269|PubMed:23530209}.;
Disease: DISEASE: Nephronophthisis 18 (NPHP18) [MIM:615862]: An autosomal recessive disorder characterized by chronic tubulointerstitial nephritis resulting in end-stage renal disease in early childhood. Extrarenal manifestations, including intellectual disability or liver changes, may occur in some patients. {ECO:0000269|PubMed:24882706}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.105

Intolerance Scores

RVIS EVS: -0.11
RVIS percentile EVS: 45.49

Essentials

Essential (gene trap): N