NDUFC2-KCTD14

Chr 11

NDUFC2-KCTD14 readthrough

NCBI Gene: 100532726 ENSG00000259112 UniProt: E9PQ53

This locus represents naturally occurring read-through transcription between the neighboring NDUFC2 (NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa) and KCTD14 (potassium channel tetramerisation domain containing 14) genes on chromosome 11. The read-through transcripts share sequence identity with the upstream gene product and one variant has a frameshifted C-terminal region derived from the downstream gene exons. [provided by RefSeq, Feb 2011]

Research

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.86LOEUF

pLI 0.657

Z-score 1.72

OE 0.00 (0.00–0.86)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.39Z-score

OE missense 0.87 (0.70–1.08)

58 obs / 66.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.86)

0≤0.351.4

Missense OE?0.87 (0.70–1.08)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 0 / 3.5Missense obs/exp: 58 / 66.9Syn Z: 0.65

Background carrier burden — how many people carry a rare variant somewhere in NDUFC2-KCTD14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

203 rare PASS variants

Rare truncating (LoF)

1 in 2,600

25 rare PASS variants

Rare synonymous (reference)

1 in 310

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFC2-KCTD14. 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 380	1 in 2,800
South Asian	~43k	1 in 380	1 in 1,200
Remaining (unassigned)	~30k	1 in 430	1 in 3,300
European (Finnish)	~27k	1 in 1,400	≈ 1 in 13,000
Admixed American	~22k	1 in 450	1 in 480
African / African American	~21k	1 in 800	1 in 1,800
East Asian	~20k	1 in 410	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 610	≈ 1 in 4,300
Middle Eastern	~2,883	1 in 240	none seen

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓