MCTP2

Chr 15

multiple C2 and transmembrane domain containing 2

NCBI Gene: 55784 ENSG00000140563 UniProt: Q6DN12

The protein enables calcium ion binding and is predicted to regulate neurotransmitter secretion, with possible roles in cardiac outflow tract development. Mutations cause autosomal recessive intellectual disability with seizures and language delay, as well as cardiac conduction defects. This gene shows low constraint against loss-of-function mutations based on population genetic data.

ResearchSummary from RefSeq, UniProt

Enables calcium ion binding activity. Predicted to be involved in regulation of neurotransmitter secretion. Located in cytosol; membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.64

LOEUF

Multiple*

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.64LOEUF

pLI 0.000

Z-score -2.23

OE 1.34 (1.10–1.64)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.42Z-score

OE missense 1.18 (1.10–1.27)

572 obs / 484.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.34 (1.10–1.64)

0≤0.351.4

Missense OE?1.18 (1.10–1.27)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 68 / 50.8Missense obs/exp: 572 / 484.3Syn Z: -0.50

Background carrier burden — how many people carry a rare variant somewhere in MCTP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,286 rare PASS variants

Rare truncating (LoF)

1 in 220

314 rare PASS variants

Rare synonymous (reference)

1 in 74

454 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MCTP2. 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 63	1 in 310
South Asian	~43k	1 in 30	1 in 160
Remaining (unassigned)	~30k	1 in 36	1 in 180
European (Finnish)	~27k	1 in 87	≈ 1 in 6,700
Admixed American	~22k	1 in 33	1 in 220
African / African American	~21k	1 in 39	1 in 260
East Asian	~20k	1 in 29	1 in 100
Ashkenazi Jewish	~13k	1 in 88	1 in 1,200
Middle Eastern	~2,884	1 in 36	1 in 110

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): 16 of 22 coding exons well covered in gnomAD exomes; exons 3, 7, 15, 20, 21, 22 marginal. Genomes: all 22.? see exons ↓