CEP164

Chr 11AR

centrosomal protein 164

Also known as: NPHP15

NCBI Gene: 22897 ENSG00000110274 UniProt: Q9UPV0 OMIM: 614848

This gene encodes a centrosomal protein that organizes microtubules, mediates DNA damage response signaling through ATR/ATM pathways, and is required for primary cilia assembly. Mutations cause nephronophthisis 15, an autosomal recessive ciliopathy affecting the kidneys. The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nephronophthisis 15MIM #614845

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · CEP164-related 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

0.84

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CEP164

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?

0.84LOEUF

pLI 0.000

Z-score 2.78

OE 0.67 (0.54–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.35Z-score

OE missense 0.97 (0.91–1.02)

779 obs / 806.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.54–0.84)

0≤0.351.4

Missense OE?0.97 (0.91–1.02)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 55 / 82.2Missense obs/exp: 779 / 806.6Syn Z: -1.33

Background carrier burden — how many people carry a rare variant somewhere in CEP164?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 21

2,400 rare PASS variants

Rare truncating (LoF)

1 in 310

411 rare PASS variants

Rare synonymous (reference)

1 in 55

915 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CEP164. 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 30	1 in 400
South Asian	~43k	1 in 19	1 in 340
Remaining (unassigned)	~30k	1 in 17	1 in 240
European (Finnish)	~27k	1 in 72	1 in 460
Admixed American	~22k	1 in 23	1 in 150
African / African American	~21k	1 in 19	1 in 190
East Asian	~20k	1 in 21	1 in 330
Ashkenazi Jewish	~13k	1 in 85	1 in 980
Middle Eastern	~2,884	1 in 21	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 30 of 31 coding exons well covered in gnomAD exomes; exon 28 marginal. Genomes: all 31.? see exons ↓