C1QTNF6

Chr 22

C1q and TNF related 6

Also known as: CTFP6, CTRP6, ZACRP6

NCBI Gene: 114904 ENSG00000133466 UniProt: Q9BXI9 OMIM: 614910

C1QTNF6 encodes a protein that enables identical protein binding and is predicted to form collagen trimers in the extracellular space. The gene shows very low constraint against loss-of-function variants (pLI = 0.000009, LOEUF = 1.623), suggesting high tolerance to complete loss of function. Based on the provided data, no specific diseases have been definitively associated with mutations in this gene.

OMIM ResearchSummary from RefSeq

Enables identical protein binding activity. Predicted to be located in extracellular region and membrane. Predicted to be part of collagen trimer. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.62

Clinical Summary— C1QTNF6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

52 VUS of 61 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.62LOEUF

pLI 0.000

Z-score 0.21

OE 0.92 (0.54–1.62)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.51Z-score

OE missense 0.89 (0.79–1.02)

168 obs / 187.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.54–1.62)

0≤0.351.4

Missense OE?0.89 (0.79–1.02)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 8 / 8.7Missense obs/exp: 168 / 187.8Syn Z: 1.08

This gene — mechanism propensity

0.6938th %ile

GOF

0.6248th %ile

LOF

0.3745th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS52

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	52	0	52
Likely Benign	3	0	3
Benign	0	2	2
Total	55	2	57

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap C1QTNF6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →