ADAM10

Chr 15

ADAM metallopeptidase domain 10

Also known as: AD10, AD18, CD156c, CDw156, HsT18717, MADM, RAK, kuz

NCBI Gene: 102 ENSG00000137845 UniProt: O14672

Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtReticulate acropigmentation of Kitamura

UniProtAlzheimer disease 18

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

248

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

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

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 5.75

OE 0.02 (0.01–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.31Z-score

OE missense 0.54 (0.48–0.60)

222 obs / 410.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.12)

0≤0.351.4

Missense OE?0.54 (0.48–0.60)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 1 / 40.5Missense obs/exp: 222 / 410.5Syn Z: -0.63

Background carrier burden — how many people carry a rare variant somewhere in ADAM10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

789 rare PASS variants

Rare truncating (LoF)

1 in 510

80 rare PASS variants

Rare synonymous (reference)

1 in 150

365 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ADAM10; this gene does not show strong loss-of-function constraint by this measure. 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 120	1 in 650
South Asian	~43k	1 in 91	1 in 260
Remaining (unassigned)	~30k	1 in 67	1 in 790
European (Finnish)	~27k	1 in 340	1 in 290
Admixed American	~22k	1 in 100	1 in 540
African / African American	~21k	1 in 90	1 in 420
East Asian	~20k	1 in 110	1 in 530
Ashkenazi Jewish	~13k	1 in 220	1 in 540
Middle Eastern	~2,884	1 in 73	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 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓