ADAM9

Chr 8AR

ADAM metallopeptidase domain 9

Also known as: CORD9, MCMP, MDC9, Mltng

NCBI Gene: 8754 ENSG00000168615 UniProt: Q13443 OMIM: 602713

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 biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene interacts with SH3 domain-containing proteins, binds mitotic arrest deficient 2 beta protein, and is also involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. Several alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cone-rod dystrophy 9MIM #612775

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ADAM9-related retinopathy · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.029

Z-score 4.81

OE 0.26 (0.17–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.90Z-score

OE missense 0.75 (0.68–0.82)

329 obs / 441.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.17–0.42)

0≤0.351.4

Missense OE?0.75 (0.68–0.82)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 13 / 49.5Missense obs/exp: 329 / 441.6Syn Z: -0.01

Background carrier burden — how many people carry a rare variant somewhere in ADAM9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

962 rare PASS variants

Rare truncating (LoF)

1 in 1,100

129 rare PASS variants

Rare synonymous (reference)

1 in 120

364 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADAM9. 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 1,700
South Asian	~43k	1 in 62	1 in 770
Remaining (unassigned)	~30k	1 in 61	1 in 5,000
European (Finnish)	~27k	1 in 200	1 in 1,200
Admixed American	~22k	1 in 51	1 in 1,800
African / African American	~21k	1 in 61	1 in 1,700
East Asian	~20k	1 in 61	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 67	≈ 1 in 2,900

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): 21 of 22 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: 21 of 22 (exon 13 below).? see exons ↓