C1QTNF5

Chr 11

C1q and TNF related 5

Also known as: CTRP5, MFRP

NCBI Gene: 114902 ENSG00000223953 UniProt: Q9BXJ0

This gene encodes a member of a family of proteins that function as components of basement membranes and may play a role in cell adhesion. Mutations in this gene have been associated with late-onset retinal degeneration. The protein may be encoded by either a bicistronic transcript including sequence from the upstream membrane frizzled-related protein gene (MFRP), or by a monocistronic transcript expressed from an internal promoter. [provided by RefSeq, Jun 2013]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLate-onset retinal degeneration

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · inherited retinal dystrophy · AD · ClinGen 2024

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.836

Z-score 2.26

OE 0.00 (0.00–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.16Z-score

OE missense 0.72 (0.61–0.85)

96 obs / 133.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.50)

0≤0.351.4

Missense OE?0.72 (0.61–0.85)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 0 / 5.9Missense obs/exp: 96 / 133.6Syn Z: 0.37

Background carrier burden — how many people carry a rare variant somewhere in C1QTNF5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 370

309 rare PASS variants

Rare truncating (LoF)

1 in 1,000

39 rare PASS variants

Rare synonymous (reference)

1 in 390

173 rare PASS variants

Rare missense and truncating variants are carried at similar rates in C1QTNF5; this gene does not show strong loss-of-function constraint by this measure. 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 590	1 in 1,600
South Asian	~43k	1 in 150	1 in 880
Remaining (unassigned)	~30k	1 in 320	1 in 1,000
European (Finnish)	~27k	1 in 850	≈ 1 in 6,100
Admixed American	~22k	1 in 220	1 in 1,000
African / African American	~21k	1 in 270	1 in 1,300
East Asian	~20k	1 in 200	1 in 900
Ashkenazi Jewish	~13k	1 in 790	none seen
Middle Eastern	~2,884	1 in 180	≈ 1 in 1,200

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓