C1QTNF12

Chr 1

C1q and TNF related 12

Also known as: C1QDC2, CTRP12, FAM132A

NCBI Gene: 388581 ENSG00000184163 UniProt: Q5T7M4 OMIM: 616593

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable hormone activity. Predicted to be involved in negative regulation of gluconeogenesis; positive regulation of D-glucose import across plasma membrane; and positive regulation of insulin receptor signaling pathway. Predicted to act upstream of or within negative regulation of inflammatory response; positive regulation of cell communication; and regulation of glucose metabolic process. Predicted to be located in extracellular region. Predicted to be active in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.64

LOEUF

Mechanism· predicted

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 OE?1.01 (0.63–1.64)

0≤0.351.4

Missense OE?1.05 (0.93–1.19)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 11 / 10.9Missense obs/exp: 177 / 168.0Syn Z: 0.22

Background carrier burden — how many people carry a rare variant somewhere in C1QTNF12?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

540 rare PASS variants

Rare truncating (LoF)

1 in 550

99 rare PASS variants

Rare synonymous (reference)

1 in 170

234 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C1QTNF12. 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 99	1 in 560
South Asian	~43k	1 in 55	1 in 640
Remaining (unassigned)	~30k	1 in 64	1 in 390
European (Finnish)	~26k	1 in 400	1 in 1,500
Admixed American	~22k	1 in 93	1 in 310
African / African American	~21k	1 in 88	1 in 480
East Asian	~20k	1 in 84	1 in 950
Ashkenazi Jewish	~13k	1 in 600	≈ 1 in 6,400
Middle Eastern	~2,883	1 in 67	1 in 410

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 8.? see exons ↓