C1QTNF12

Chr 1

C1q and TNF related 12

Also known as: C1QDC2, CTRP12, FAM132A

NCBI Gene: 388581ENSG00000184163UniProt: Q5T7M4

C1QTNF12 encodes an insulin-sensitizing adipokine that regulates glucose metabolism by promoting glucose uptake in adipocytes and suppressing hepatic glucose production via the PI3K-Akt signaling pathway. Mutations cause autosomal recessive familial partial lipodystrophy type 7, characterized by loss of subcutaneous fat from the limbs and trunk with metabolic complications including insulin resistance and diabetes. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance patterns.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
137
P/LP submissions
0%
P/LP missense
1.64
LOEUF
DN
Mechanism· predicted
Clinical Summary— C1QTNF12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
130 unique Pathogenic / Likely Pathogenic· 105 VUS of 257 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
1.64LOEUF
pLI 0.000
Z-score -0.03
OE 1.01 (0.63–1.64)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.25Z-score
OE missense 1.05 (0.93–1.19)
177 obs / 168.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.01 (0.63–1.64)
0≤0.351.4
Missense OE1.05 (0.93–1.19)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 11 / 10.9Missense obs/exp: 177 / 168.0Syn Z: 0.22
DN
0.6454th %ile
GOF
0.5562th %ile
LOF
0.3746th %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

257 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic124
Likely Pathogenic6
VUS105
Likely Benign6
Benign3
124
Pathogenic
6
Likely Pathogenic
105
VUS
6
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
124
0
124
Likely Pathogenic
0
0
6
0
6
VUS
0
86
19
0
105
Likely Benign
0
5
1
0
6
Benign
0
2
0
1
3
Total0931501244

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

View in ClinVar →

Protein Context — Lollipop Plot

C1QTNF12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients