ADAM23

Chr 2

ADAM metallopeptidase domain 23

Also known as: MDC-3, MDC3

NCBI Gene: 8745ENSG00000114948UniProt: O75077

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. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

131
ClinVar variants
27
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ADAM23
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 89 VUS of 131 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.997
Z-score 5.69
OE 0.15 (0.09–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.90Z-score
OE missense 0.75 (0.68–0.82)
329 obs / 441.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.09–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.68–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.75
0≤1.21.6
LoF obs/exp: 8 / 52.4Missense obs/exp: 329 / 441.3Syn Z: 2.45

ClinVar Variant Classifications

131 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS89
Likely Benign13
Benign2
26
Pathogenic
1
Likely Pathogenic
89
VUS
13
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
1
0
1
VUS
1
85
3
0
89
Likely Benign
0
7
1
5
13
Benign
0
0
1
1
2
Total192326131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ADAM23 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biallelic LGI1 and ADAM23 variants cause hippocampal epileptic encephalopathy via the LGI1-ADAM22/23 pathway.
Hirano Y et al.·Brain
2025
ADAM23 haploinsufficiency as a putative oligogenic contributor in an individual with focal epilepsy.
Krenn M et al.·Seizure
2025Case report
Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals.
Costa ET et al.·Oncogene
2015
ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells.
Ota M et al.·Cancer Sci
2016
CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers.
Fridrichova I et al.·Transl Res
2015
Decreased methylation in the SNAI2 and ADAM23 genes associated with de-differentiation and haematogenous dissemination in breast cancers.
Kalinkova L et al.·BMC Cancer
2018
ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis.
Verbisck NV et al.·Cancer Res
2009
Gene methylation in gastric cancer.
Qu Y et al.·Clin Chim Acta
2013Review
Prognostic value of tumour microenvironment-related genes by TCGA database in rectal cancer.
Li C et al.·J Cell Mol Med
2021
Histone H3.3K27M Mobilizes Multiple Cancer/Testis (CT) Antigens in Pediatric Glioma.
Deng H et al.·Mol Cancer Res
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools