ADAM18

Chr 8

ADAM metallopeptidase domain 18

Also known as: ADAM27, tMDCIII

NCBI Gene: 8749 ENSG00000168619 UniProt: Q9Y3Q7 OMIM: 619495

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature sperm surface protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.57

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.57LOEUF

pLI 0.000

Z-score -1.32

OE 1.23 (0.97–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.58Z-score

OE missense 1.08 (1.00–1.18)

406 obs / 374.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.23 (0.97–1.57)

0≤0.351.4

Missense OE?1.08 (1.00–1.18)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 47 / 38.2Missense obs/exp: 406 / 374.5Syn Z: -1.49

Background carrier burden — how many people carry a rare variant somewhere in ADAM18?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

1,025 rare PASS variants

Rare truncating (LoF)

1 in 240

203 rare PASS variants

Rare synonymous (reference)

1 in 100

359 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ADAM18; 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 52	1 in 310
South Asian	~43k	1 in 42	1 in 390
Remaining (unassigned)	~30k	1 in 43	1 in 150
European (Finnish)	~27k	1 in 180	1 in 1,900
Admixed American	~22k	1 in 56	1 in 310
African / African American	~21k	1 in 47	1 in 370
East Asian	~20k	1 in 71	1 in 590
Ashkenazi Jewish	~13k	1 in 170	1 in 500
Middle Eastern	~2,884	1 in 38	1 in 290

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.