CEP83

Chr 12AR

centrosomal protein 83

Also known as: CCDC41, NPHP18, NY-REN-58

NCBI Gene: 51134 ENSG00000173588 UniProt: Q9Y592 OMIM: 615847

The encoded protein is a centriolar component that initiates primary cilium assembly and collaborates with IFT20 in trafficking ciliary membrane proteins from the Golgi complex to the cilium. Mutations cause nephronophthisis 18, an infantile kidney disorder that can be associated with intellectual disability. The condition follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nephronophthisis 18MIM #615862

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ciliopathy · AR · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.89

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CEP83

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 2.12

OE 0.65 (0.48–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.41Z-score

OE missense 0.94 (0.85–1.03)

316 obs / 337.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.48–0.89)

0≤0.351.4

Missense OE?0.94 (0.85–1.03)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 28 / 43.0Missense obs/exp: 316 / 337.0Syn Z: -0.95

Background carrier burden — how many people carry a rare variant somewhere in CEP83?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

773 rare PASS variants

Rare truncating (LoF)

1 in 890

163 rare PASS variants

Rare synonymous (reference)

1 in 230

283 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CEP83. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 81	1 in 920
South Asian	~43k	1 in 90	1 in 1,100
Remaining (unassigned)	~30k	1 in 60	1 in 340
European (Finnish)	~27k	1 in 200	1 in 2,700
Admixed American	~22k	1 in 62	1 in 860
African / African American	~21k	1 in 83	1 in 730
East Asian	~20k	1 in 85	1 in 570
Ashkenazi Jewish	~13k	1 in 340	1 in 1,600
Middle Eastern	~2,884	1 in 65	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 15 coding exons well covered in gnomAD exomes; exons 5, 6, 8, 9, 12 and 2 more marginal. Genomes: all 15.? see exons ↓